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Parkinson Disease: HELP
Articles by Fabrizio Stocchi
Based on 84 articles published since 2008
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Between 2008 and 2019, F. Stocchi wrote the following 84 articles about Parkinson Disease.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson's disease. 2018

Stocchi, Fabrizio / Vacca, Laura / Stirpe, Paola / Torti, Margherita. ·a Departement of Neurology , University and Institute for Research and Medical Care, San Raffaele Rome , Roma , Italy. · b Department of Neurorehabilitation Sciences , Casa Cura Policlinico (CCP) , Milan , Italy. · c Departement of Neurology , Institute for Research and Medical Care, San Raffaele Cassino , Cassino (FR) , Italy. ·Expert Opin Drug Metab Toxicol · Pubmed #30479171.

ABSTRACT: INTRODUCTION: Levodopa (LD), in combination with a decarboxylase inhibitor, is a mainstay and the most effective therapeutic agent in the treatment of Parkinson's disease (PD). Unfortunately, during chronic treatment with this agent, ON-OFF phenomena and dyskinesia appear. Despite the many medical treatment options available, unpredictable OFF episodes can still occur and be severe and disabling. A rescue therapy that provides a rapid and predictable ON response for patients with OFF periods would be of great value for such patients. Areas covered: CVT-301 is a self-administered dry powder aerosol inhaled formulation of LD that is being developed as a self-administered treatment for OFF periods. The PK profile of CVT-301, the efficacy, and the safety highlighted in randomized clinical trials will be reviewed. Expert opinion: CVT-301 may offer several potential advantages including increased systemic bioavailability through pulmonary absorption, rapid onset of action, avoidance of first-pass drug metabolism and less plasma-level variability. List of Abbreviations: PD: Parkinson's disease; LD: Levodopa; CD: Carbidopa; AADC: aromatic L-amino acid decarboxylase; IR: immediate-release; FPD: fine particle dose; GI: gastrointestinal; PK: pharmacokinetic; CVs: coefficient of variation; UPDRS: Unified Parkinson's Disease Rating Scale; AEs: adverse events; FEV: forced expiratory volume; FVC: forced vital capacity; DL

2 Review Istradefylline for the treatment of Parkinson's disease: is it a promising strategy? 2018

Torti, Margherita / Vacca, Laura / Stocchi, Fabrizio. ·a Center for Parkinson's Disease , IRCCS San Raffaele Pisana , Rome , Italy. · b Neurology Department , San Raffaele Cassino , Cassino , Italy. · c Neurology Department , Casa di Cura Privata Policlinico (CCPP) , Milan , Italy. · d Neurology Department , San Raffaele University , Rome , Italy. ·Expert Opin Pharmacother · Pubmed #30232916.

ABSTRACT: INTRODUCTION: Istradefylline (ISD) is a new drug developed for the treatment of Parkinson's disease (PD). It is an adenosine receptor A

3 Review Constipation in Parkinson's Disease. 2017

Stocchi, Fabrizio / Torti, Margherita. ·University and Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy. Electronic address: fabrizio.stocchi@fastwebnet.it. · University and Institute for Research and Medical Care, IRCCS San Raffaele, Rome, Italy. Electronic address: margherita.torti@sanraffaele.it. ·Int Rev Neurobiol · Pubmed #28805584.

ABSTRACT: Constipation is one of the main and disabling nonmotor symptoms in Parkinson's disease (PD), with a prevalence ranging from 24.6% to 63% according to the different diagnostic criteria used to define chronic constipation. Constipation is currently recognized as a risk factor of PD in relation to the number of evacuation per week and its severity. Moreover, several studies have demonstrated that constipation may precede the occurrence of motor symptoms underlying an earlier involvement of the enteric nervous system and the dorsal motor nucleus of the vagus in the α-synuclein pathology. In PD, constipation is mainly due to slower colonic transit or puborectalis dyssynergia, but the concomitant use of antiparkinsonian, pain, and antidepressant medications may worsen it. An accurate diagnosis and an adequate treatment of constipation it is pivotal to prevent complications such as intestinal occlusion and to ensure an optimal clinical response to levodopa.

4 Review Opicapone for the management of end-of-dose motor fluctuations in patients with Parkinson's disease treated with L-DOPA. 2017

Lees, Andrew J / Ferreira, Joaquim / Rascol, Olivier / Reichmann, Heinz / Stocchi, Fabrizio / Tolosa, Eduardo / Poewe, Werner. ·a Reta Lila Weston Institute for Neurological Studies, UCL , London , UK. · b Centro de Estudos Egas Moniz , Hospital de Santa Maria , Lisbon , Portugal. · c Departments of Clinical Pharmacology and Neurosciences, Clinical Investigation Center CIC 1436, NS-Park/FCRIN network and NeuroToul COEN Center , INSERM, Toulouse University Hospital and Toulouse3 University , Toulouse , France. · d Department of Neurology , Technische Universitaet Dresden , Dresden , Germany. · e Institute of Neurology , IRCCS San Raffaele Pisana , Rome , Italy. · f Neurology Service, Centro de Investigación Biomódica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), Hospital Clínic, IDIBAPS , Universitat de Barcelona , Barcelona , Spain ​​​​. · g Department of Neurology , Innsbruck Medical University , Innsbruck , Austria. ·Expert Rev Neurother · Pubmed #28580819.

ABSTRACT: INTRODUCTION: Opicapone is a third generation, highly potent and effective catechol O‑methyltransferase (COMT) inhibitor that optimizes the pharmacokinetics and bioavailability of L-DOPA therapy. Areas covered: In this review, the authors describe the preclinical and clinical development of opicapone. In PD patients with motor fluctuations, once daily opicapone administration was well-tolerated and consistently reduced OFF-time and increased ON-time without increasing the frequency of troublesome dyskinesia, and these benefits were maintained over at least a year of continued open-label therapy. Expert commentary: With its convenient once-daily regimen, adjunct opicapone should be considered as an effective option for use in L-DOPA treated PD patients experiencing motor fluctuations.

5 Review Advances in dopamine receptor agonists for the treatment of Parkinson's disease. 2016

Stocchi, Fabrizio / Torti, Margherita / Fossati, Chiara. ·a Department of Neurology, Institute for research and medical care , IRCCS San Raffaele Roma , Roma , Italy. ·Expert Opin Pharmacother · Pubmed #27561098.

ABSTRACT: INTRODUCTION: Dopamine agonists (DA) are a class of agents which directly stimulate dopamine receptors mimicking the endogenous neurotransmitter dopamine. At first used as adjunctive therapy in the advanced phases of the disease, over the years a significant role was found for DA monotherapy as a first approach in the initial stage of Parkinson's disease (PD). Several reviews have already reported efficacy and safety of DA in PD and differences between DA and levodopa. Therefore the objective of this review is to gather recent updates in DA therapy. A thorough knowledge of recent literature evidences, would help clinician in the management of treatment with DA. AREAS COVERED: Our review investigates recent updates on DA therapy, the role of these compounds in controlling non-motor symptoms (NMS) as well as new formulations under clinical evaluation and newly emerged post-marketing safety considerations. A literature search has been performed using Medline and reviewing the bibliographies of selected articles. EXPERT OPINION: DA represents a very important option in the treatment of PD, even though there are still some criticisms and unmet needs. A better knowledge of dopamine receptors could lead to identification of new compounds able to better balance clinical efficacy and side effects.

6 Review Adjuvant therapies for Parkinson's disease: critical evaluation of safinamide. 2016

Stocchi, Fabrizio / Torti, Margherita. ·Institute for Research and Medical Care, IRCCS San Raffaele Pisana, Rome, Italy. ·Drug Des Devel Ther · Pubmed #26917951.

ABSTRACT: Safinamide (SAF) is a new drug developed for the treatment of Parkinson's disease (PD). It is a benzylamino derivative with multiple mechanisms of action and antiparkinsonian, anticonvulsant, and neuroprotective properties. SAF inhibits monoamine oxidase B and dopamine reuptake and glutamate release, blocks voltage-dependent sodium channels, and modulates calcium channels. Although the antiparkinsonian effect can be ascribed in part to the inhibition of the monoamine oxidase B, which is complete at 50 mg, the enhanced benefit seen at the 100 mg dose is probably due to nondopaminergic mechanisms. SAF will represent an important option for patients with both early and advanced PD. In early PD patients, the addition of SAF to dopamine agonists may be an effective treatment strategy to improve motor function, prolong the use of dopamine agonists, and/or delay the introduction of levodopa. In advanced parkinsonian patients, SAF has been demonstrated to significantly increase on time with no, or nontroublesome dyskinesias. All studies performed have demonstrated its efficacy in benefiting both short-term and long-term quality-of-life outcomes in both early and advanced PD patients. SAF has been investigated in long-term (24 months), double-blind, placebo-controlled studies, where it showed a very good safety profile. SAF has not been studied in de novo PD patients, and its potential positive effect on dyskinesia deserves further dedicated studies.

7 Review Rasagiline for the treatment of Parkinson's disease: an update. 2015

Stocchi, Fabrizio / Fossati, Chiara / Torti, Margherita. ·a Institute for Research and Medical Care, IRCCS San Raffaele Rome - Neurology , Rome, Italy fabrizio.stocchi@tin.it. ·Expert Opin Pharmacother · Pubmed #26364897.

ABSTRACT: INTRODUCTION: Rasagiline is a potent, selective, irreversible Monoamine Oxidase-B (MAO-B) inhibitor, developed to prolong the action of dopamine in the brain. It has been demonstrated that rasagiline can improve motor and some non-motor symptoms (NMS) in both early and advanced Parkinson's disease (PD) patients, and it also exhibits neuroprotective and antiapoptotic properties. AREAS COVERED: The objective of this review, performed by a Medline search on the most recent papers investigating the therapeutic effects of rasagiline, is to describe the role of rasagiline in the schedule of treatment of early and advanced PD patients. It will then focus on its role in treating NMS, fatigue, early morning off and cognitive decline, which heavily affect quality of life for PD patients. EXPERT OPINION: Rasagiline is an efficacious, well-tolerated, easy to use drug. The drug has been extensively studied and has proven its efficacy in monotherapy and in combination with any other antiparkinsonian therapy. It proved to be efficacious in reducing 'off' time and in improving early morning 'off' but also some NMS, thus enhancing the therapeutic approach to PD.

8 Review The relevance of dopaminergic level in nocturnal disability in Parkinson's disease: implications of continuous dopaminergic stimulation at night to treat the symptoms. 2014

Stocchi, Fabrizio / Stirpe, Paola. ·Institute for Research and Medical Care IRCCS San Raffaele, Via della Pisana 235, 00163, Rome, Italy, fabrizio.stocchi@fastwebnet.it. ·J Neural Transm (Vienna) · Pubmed #24990308.

ABSTRACT: Sleep problems are an under-emphasized cause of disability in Parkinson's disease (PD). Difficult sleep maintenance (light and fragmented sleep) and difficulties in initiating sleep are often the earliest and the most frequent symptoms observed in PD patients. In fluctuating patients, nocturnal akinesia, dystonia, painful cramps, and parasomnias may aggravate nocturnal problems. Treatment of sleep problems can be complex and challenging for the physicians. Dopaminergic treatment may improve some of the nocturnal symptoms in PD. In this paper, the effect of drugs and technique that ensure a more continuous delivery of dopaminergic drugs on sleep problems in PD is reviewed.

9 Review Drug safety evaluation of ropinirole prolonged release. 2014

Stocchi, Fabrizio / Radicati, Fabiana G / Torti, Margherita. ·Institute of Research and Medical Care, IRCCS San Raffaele Roma , via della Pisana 235, 00163 Rome , Italy +39 336 909 255 ; +39 066 789158 ; fabrizio.stocchi@fastwebnet.it. ·Expert Opin Drug Saf · Pubmed #24490799.

ABSTRACT: INTRODUCTION: The need for multiple administrations and a difficult titration schedule has always represented a limit in the use of dopamine agonists in the treatment of early Parkinson's disease. To avoid these problems, Ropinirole prolonged release (RPR), a non-ergoline dopamine receptor agonist that can be taken once a day, has been formulated. The prolonged release formulation has higher patient compliance due to a simpler and fastest titration schedule; the once-a-day administration makes this molecule especially suitable for young Parkinsonian patients who are still working and having an active lifestyle. AREAS COVERED: In this paper, we will review ropinirole's mechanism of action including pharmacokinetics and pharmacodynamic data and the results of the main clinical studies in early and advanced PD patients. We will also discuss safety data shown during the experimental phase and after RPR commercialization. This article reviews the use of RPR in early and advanced Parkinsonian patients. Medical literature on the use of RPR in Parkinson's disease was identified using MEDLINE and the reference lists of published articles. EXPERT OPINION: RPR is effective in the treatment of patients with early Parkinson's disease; in advanced Parkinsonian patients, the amount of daily off-time significantly decreases, improving the mean on time. RPR has also demonstrated to be effective in ameliorating the quality of sleep without increasing the occurrence of daily sleepiness and nocturnal psychosis. RPR was generally well tolerated in both early and advanced Parkinsonian patients.

10 Review Therapy for Parkinson's disease: what is in the pipeline? 2014

Stocchi, Fabrizio. ·Institute for Research and Medical Care, IRCCS San Raffaele, Via della Pisana 235, 00163, Rome, Italy, fabrizio.stocchi@fastwebnet.it. ·Neurotherapeutics · Pubmed #24343458.

ABSTRACT: Despite advances in the treatment of Parkinson's disease there are still many unmet needs, including neuroprotection, treatment of motor complications, treatment of dyskinesia, treatment of psychosis, and treatment of nondopaminergic symptoms. In this review, I highlight the obstacles to develop a neuroprotective drug and some of the treatment strategies recently approved or still in clinical trials designed to meet these unmet needs.

11 Review Obstacles to the development of a neuroprotective therapy for Parkinson's disease. 2013

Stocchi, Fabrizio / Olanow, C Warren. ·IRCCS San Raffaele Pisana, Rome, Italy. ·Mov Disord · Pubmed #23390094.

ABSTRACT: A neuroprotective or disease-modifying therapy that can slow or stop disease progression and prevent the development of intolerable disability is the major unmet medical need in the treatment of Parkinson's disease (PD). Many putative neuroprotective agents have been identified in the laboratory, but none has been unequivocally demonstrated to provide disease-modifying effects in PD patients, even when clinical trials are positive. Obstacles to defining a neuroprotective therapy in PD include: (1) uncertainty about the cause of PD and precisely what to target, (2) a reliable animal model in which to test putative neuroprotective agents that accurately predicts results in PD patients, (3) insight about which dose to employ in clinical trials and which patient group to study, (4) a clinical trial design that reliably differentiates disease-modifying and symptomatic effects and that is acceptable to regulatory authorities, and (5) the cost and time of the development program. Advances have been made in each of these areas, thereby increasing the prospects of developing a neuroprotective or disease-modifying therapy in the not-too-distant future. These issues are reviewed in the present article.

12 Review Wearing-off scales in Parkinson's disease: critique and recommendations. 2011

Antonini, Angelo / Martinez-Martin, Pablo / Chaudhuri, Ray K / Merello, Marcelo / Hauser, Robert / Katzenschlager, Regina / Odin, Per / Stacy, Mark / Stocchi, Fabrizio / Poewe, Werner / Rascol, Oliver / Sampaio, Cristina / Schrag, Anette / Stebbins, Glenn T / Goetz, Christopher G. ·Department for Parkinson's Disease and Movement Disorders, IRCCS "San Camillo," Venice, Italy. angelo3000@yahoo.com ·Mov Disord · Pubmed #21780180.

ABSTRACT: Wearing-off occurs in the majority of patients with Parkinson's disease after a few years of dopaminergic therapy. Because a variety of scales have been used to estimate wearing-off, the Movement Disorder Society commissioned a task force to assess their clinimetric properties. A systematic review was conducted to identify wearing-off scales that have either been validated or used in Parkinson's patients. A scale was designated "Recommended" if it had been used in clinical studies beyond the group that developed it, if it had been specifically used in Parkinson's disease reports, and if clinimetric studies had established that it is valid, reliable, and sensitive. "Suggested" scales met 2 of the above criteria, and those meeting 1 were "Listed." We identified 3 diagnostic and 4 severity rating scales for wearing-off quantification. Two questionnaires met the criteria to be Recommended for diagnostic screening (questionnaires for 19 and 9 items), and 1 was Suggested (questionnaire for 32 items). Only the patient diaries were Recommended to assess wearing-off severity, with the caveat of relatively limited knowledge of validity. Among the other severity assessment tools, the Unified Parkinson Disease Rating Scale version 3 and the version revised from the Movement Disorders Society were classified as Suggested, whereas the Treatment Response Scale was Listed.

13 Review Continuous dopaminergic stimulation and novel formulations of dopamine agonists. 2011

Stocchi, Fabrizio. ·Institute of Neurology, Institute for Research and Medical Care IRCCS San Raffaele, Via della Pisana 235, 00163 Rome, Italy. fabrizio.stocchi@fastwebnet.it ·J Neurol · Pubmed #21560062.

ABSTRACT: There is now accumulating evidence that the combination of progressive pathology of Parkinson's disease, the change in drug pharmacodynamics, and the pulsatile manner in which short-acting dopaminergic agents stimulate striatal dopamine receptors are the key contributing factors to the priming of the basal ganglia for induction of motor complications. Long-acting drugs provide a more physiological dopaminergic stimulation. Dopamine agonists have been extensively used as monotherapy and add-on therapy to levodopa to treat Parkinson's disease in the early stage and with motor complications. Today, the new long-acting formulation offers the advantages of an easy use and a more continuous delivery of drug. In this paper the role of new formulations of dopamine agonists in the treatment of parkinsonian patients at different stages of the disease is reviewed.

14 Review Factors associated with motor fluctuations and dyskinesia in Parkinson Disease: potential role of a new melevodopa plus carbidopa formulation (Sirio). 2010

Stocchi, Fabrizio / Marconi, Stefano. ·IRCCS San Raffaele Pisana, Rome; and daggerMedical Department, Chiesi Farmaceutici S.p.A., Parma, Italy. stocchi@sanraffaele.it ·Clin Neuropharmacol · Pubmed #20414107.

ABSTRACT: Parkinson disease is a progressive movement disorder caused by loss of dopaminergic neurons in the substantia nigra. Of unknown etiology, Parkinson disease is characterized by 4 cardinal symptoms: tremor at rest, bradykinesia, postural instability, and rigidity. The current criterion-standard drug used in the management of parkinsonian symptoms is levodopa (l-dopa). However, long-term l-dopa therapy is associated with the development of motor complications; approximately 50% to 80% of patients will develop motor complications within 5 to 10 years of l-dopa treatment initiation. Motor complications can be divided into motor fluctuations, caused largely through pulsatile dopamine stimulation and low l-dopa concentrations, and dyskinesia, associated more often with peak l-dopa concentrations. Ultimately, the main goal was to provide steady l-dopa concentrations, without peaks and troughs. Empirical investigations using parenteral infusions of l-dopa and highly soluble l-dopa prodrugs have shown that there is benefit in ameliorating the peaks and troughs associated with traditional oral l-dopa formulations. Recently, the development of highly soluble oral l-dopa prodrugs has facilitated rapid, regular, and reliable l-dopa availability. This review evaluates some of the pharmacologic strategies in the management of motor complications in Parkinson disease and therapy optimization, with a focus on the use of CHF 1512 (Sirio), a combination of melevodopa (l-dopa methylester, a highly soluble prodrug of l-dopa) plus carbidopa in an effervescent tablet formulation.

15 Review When do levodopa motor fluctuations first appear in Parkinson's disease? 2010

Stocchi, Fabrizio / Jenner, Peter / Obeso, Jose A. ·Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy. fabrizio.stocchi @ sanraffaele.it ·Eur Neurol · Pubmed #20332641.

ABSTRACT: Although levodopa provides therapeutic benefit over the entire course of Parkinson's disease, most patients eventually notice a decline in the duration of benefit from each dose, a phenomenon termed 'wearing-off' or 'end of dose' deterioration. This is an important indicator that the patient is entering a more complex phase of the disease. Wearing-off has been classically associated with the later stages of Parkinson's disease, but it is becoming apparent that patients with early disease, presenting as well controlled, may already be experiencing fluctuations in their response to levodopa. However, neither the pathophysiology nor the clinical relevance of the early emergence of wearing-off has been properly explored. We now review the preclinical and clinical evidence that suggests that even patients who are apparently still in the honeymoon phase of drug treatment may have early fluctuations in their motor response to dopaminergic therapy. It is important that early wearing-off is recognized as it has important consequences for the long-term outcome and for the medication regimens to be used.

16 Review Dopamine receptor agonists in the treatment of advanced Parkinson's disease. 2009

Stocchi, Fabrizio. ·Institute of Neurology, IRCCS San Raffaele, Rome, Italy. fabrizio.stocchi@fastwebnet.it ·Parkinsonism Relat Disord · Pubmed #20123558.

ABSTRACT: The symptoms of Parkinson's disease (PD) can become increasingly difficult to control as the disease advances. L-dopa is the most efficacious therapy; however, with long-term therapy, motor and non-motor complications develop. There is now accumulating evidence that the progressive pathology of PD, the change in drug pharmaco-dynamics, and the pulsatile manner in which short-acting dopaminergic agents stimulate striatal dopamine receptors combine as key contributing factors to the priming of the basal ganglia for induction of motor complications. Dopamine receptor agonists have been extensively used as add-on therapy to L-dopa to treat motor complications. In this article we review the role of dopamine receptor agonists in the treatment of advanced parkinsonian patients.

17 Review The therapeutic concept of continuous dopaminergic stimulation (CDS) in the treatment of Parkinson's disease. 2009

Stocchi, Fabrizio. ·Department of Neurology, IRCCS San Raffaele Pisana, Rome, Italy. fabrizio.stocchi@sanraffaele.it ·Parkinsonism Relat Disord · Pubmed #20083012.

ABSTRACT: Continuous dopaminergic stimulation is a therapeutic concept for the management of Parkinson's disease (PD) that proposes that continuous, as opposed to discontinuous or pulsatile, stimulation of striatal dopamine receptors will delay or prevent the onset of levodopa-related motor complications. This hypothesis has arisen from studies of the normal basal ganglia demonstrating that nigral dopaminergic neurons normally fire continuously and striatal dopamine levels are relatively constant. In MPTP monkeys, pulsatile stimulation of striatal dopamine receptors with short-acting agents is associated with the induction of molecular and physiologic changes in basal ganglia neurons and the development of motor complications. These are avoided when dopaminergic therapies are delivered in a more continuous manner. Studies in animal models support this hypothesis, demonstrating that long-acting dopamine agonists are associated with a decreased risk of motor complications in comparison to short-acting formulations of levodopa. Similarly, continuous infusion of dopamine agonists ropinirole and rodigotine reduces dyskinesia associated with intermittent doses of oral formulations of the same drug. The current challenge is to develop a long-acting formulation of levodopa that simulates the pharmacokinetic pattern seen with infusions of levodopa in attempt to provide comparable benefits with an oral levodopa treatment strategy.

18 Review The hypothesis of the genesis of motor complications and continuous dopaminergic stimulation in the treatment of Parkinson's disease. 2009

Stocchi, Fabrizio. ·Institute of Neurology, IRCCS "San Raffaele", Rome, Italy. fabrizio.stocchi@fastwebnet.it ·Parkinsonism Relat Disord · Pubmed #19131046.

ABSTRACT: The symptoms of Parkinson's disease can become increasingly difficult to control as the disease advances. Levodopa remains the most efficacious therapy for symptomatic treatment. However, with long-term therapy motor and non-motor complications develop. There is now accumulating evidence that several factors - the progressive pathology of Parkinson's disease, the change in drug pharmacodynamics, and the pulsatile manner in which short-acting dopaminergic agents stimulate striatal dopamine receptors - are key contributors to the priming of the basal ganglia for induction of motor complications. In this paper, an overview of the different factors inducing motor fluctuations and the role of dopamine receptors stimulation is provided.

19 Review Use of apomorphine in Parkinson's disease. 2008

Stocchi, Fabrizio. ·Department of Neurology, IRCCS San Raffaele Pisana, Rome, Italy. fabrizio.stocchi@sanraffaele.it ·Neurol Sci · Pubmed #19381769.

ABSTRACT: In the parkinsonian patient, the striatal levels of dopamine strictly depend on peripheral levodopa levels; short half-life of levodopa is responsible for plasmatic level fluctuations, which are consistent with a pulsatile receptor stimulation of the striatal system. This sort of non-physiologic stimulation induces a change of the condition of post-synaptic neurons, which is considered responsible for the fluctuations of clinical response. In this respect, apomorphine administration, via infusion pump, may be a good therapeutic option, aimed at obtaining continuous receptor stimulation, assisting in the management of motor fluctuations in the advanced phase of the disease.

20 Review Treatment of levodopa-induced motor complications. 2008

Stocchi, Fabrizio / Tagliati, Michele / Olanow, C Warren. ·IRCCS San Raffaele, Via della Pisana 235, Roma, Italy. fabrizio.stocchi@fastwebnet.it ·Mov Disord · Pubmed #18781681.

ABSTRACT: Chronic levodopa treatment for Parkinson's disease patients is frequently associated with the development of motor complications such as end-of-dose wearing-off and dyskinesias. In this review, we provide an overview of the strategies available for dealing with these problems. Medical management includes manipulation of levodopa dosing to establish the optimum treatment schedule, improving levodopa absorption, catechol-O-methyl transferase-inhibition (COMT), Monoamine oxidase-B (MAO-B) inhibition, dopaminergic agonists, amantadine, and continuous dopaminergic infusions. Surgical procedures and particularly deep brain stimulation are also reviewed. It should be noted that none of these treatments has been shown to provide anti-parkinsonian efficacy that is greater than what can be achieved with levodopa. We highlight the importance of initiating therapy with a treatment strategy that reduces the risk that a Parkinson's disease patient will develop motor complications in the first place. Key Words: Advanced PD, dyskinesias, motor fluctuations, levodopa, dopamine agonists, COMT inhibitors, MAO-B inhibitors.

21 Clinical Trial Randomized trial of preladenant, given as monotherapy, in patients with early Parkinson disease. 2017

Stocchi, Fabrizio / Rascol, Olivier / Hauser, Robert A / Huyck, Susan / Tzontcheva, Anjela / Capece, Rachel / Ho, Tony W / Sklar, Peter / Lines, Christopher / Michelson, David / Hewitt, David J / Anonymous560906. ·From the Institute of Neurology (F.S.), IRCCS San Raffaele, Rome, Italy · Departments of Clinical Pharmacology and Neurosciences (O.R.), Clinical Investigation Center CIC1436, NS-Park Clinical Research Network, NeuroToul Centre of Excellence in Neurodegeneration, INSERM, Toulouse University Hospital and Toulouse University, France · Parkinson's Disease and Movement Disorders Center (R.A.H.), USF Health-Byrd Institute, Tampa, FL · and Merck & Co., Inc. (S.H., A.T., R.C., T.W.H., P.S., C.L., D.M., D.J.H.), Kenilworth, NJ. ·Neurology · Pubmed #28490648.

ABSTRACT: OBJECTIVE: To evaluate the adenosine 2a receptor antagonist preladenant as a nondopaminergic drug for the treatment of Parkinson disease (PD) when given as monotherapy. METHODS: This was a randomized, 26-week, placebo- and active-controlled, parallel-group, multicenter, double-blind trial conducted in adults diagnosed with PD for <5 years who were not yet receiving l-dopa or dopamine agonists. Patients with a Unified Parkinson's Disease Rating Scale (UPDRS) part 3 (motor function) score ≥10 and Hoehn & Yahr score ≤3 were randomized 1:1:1:1:1 to preladenant 2, 5, or 10 mg twice daily, rasagiline 1 mg (active-control) once daily, or placebo. The primary endpoint was the change from baseline at week 26 in the sum of UPDRS parts 2 (activities of daily living) and 3 scores (UPDRS RESULTS: The number of patients treated was 1,007. Neither preladenant nor rasagiline was superior to placebo after 26 weeks. The differences vs placebo (95% confidence interval) in UPDRS CONCLUSIONS: No evidence supporting the efficacy of preladenant as monotherapy was observed in this phase 3 trial. The lack of efficacy of the active control rasagiline makes it difficult to interpret the results. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov: NCT01155479. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with early PD, preladenant is not effective as monotherapy at the doses studied (2, 5, 10 mg).

22 Clinical Trial Mavoglurant in Parkinson's patients with l-Dopa-induced dyskinesias: Two randomized phase 2 studies. 2016

Trenkwalder, Claudia / Stocchi, Fabrizio / Poewe, Werner / Dronamraju, Nalina / Kenney, Chris / Shah, Amy / von Raison, Florian / Graf, Ana. ·Paracelsus-Elena Klinik, Kassel 34128, Germany; Department of Neurosurgery, University Medical Center, Goettingen, Germany. · IRCCS San Raffaele Pisana, Rome, Italy. · Department of Neurology, Medical University, Innsbruck, Austria. · Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. · Novartis Pharma AG, Basel, Switzerland. ·Mov Disord · Pubmed #27214258.

ABSTRACT: BACKGROUND: Two phase 2 randomized, double-blind studies were designed to evaluate efficacy and safety of immediate-release (study 1) and modified-release (study 2) mavoglurant formulations in PD l-dopa-induced dyskinesia. METHODS: Patients were randomized to mavoglurant 100-mg or placebo (4:3) groups (study 1) and mavoglurant 200-mg, mavoglurant 150-mg, or placebo (2:1:1) groups (study 2). Primary outcome was antidyskinetic efficacy, as measured by change from baseline to week 12 in modified Abnormal Involuntary Movement Scale total score. RESULTS: Differences in least-squares mean (standard error) change in modified Abnormal Involuntary Movement Scale total score in week 12 did not reach statistical significance in either study (study 1: mavoglurant 100 mg twice a day versus placebo, 1.7 [1.31]; study 2: mavoglurant 150 mg twice a day (-1.3 [1.16]) and 200 mg twice a day (-0.2 [1.03]) versus placebo). Adverse events incidence was higher with mavoglurant than with placebo. CONCLUSIONS: Both studies failed to meet the primary objective of demonstrating improvement of dyskinesia with mavoglurant treatment. © 2016 International Parkinson and Movement Disorder Society.

23 Clinical Trial A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia. 2016

Trenkwalder, Claudia / Berg, Daniela / Rascol, Olivier / Eggert, Karla / Ceballos-Baumann, Andres / Corvol, Jean-Christophe / Storch, Alexander / Zhang, Lin / Azulay, Jean-Philippe / Broussolle, Emmanuel / Defebvre, Luc / Geny, Christian / Gostkowski, Michal / Stocchi, Fabrizio / Tranchant, Christine / Derkinderen, Pascal / Durif, Franck / Espay, Alberto J / Feigin, Andrew / Houeto, Jean-Luc / Schwarz, Johannes / Di Paolo, Thérèse / Feuerbach, Dominik / Hockey, Hans-Ulrich / Jaeger, Judith / Jakab, Annamaria / Johns, Donald / Linazasoro, Gurutz / Maruff, Paul / Rozenberg, Izabela / Sovago, Judit / Weiss, Markus / Gomez-Mancilla, Baltazar. ·Paracelsus-Elena Hospital, Kassel, Germany. · Department of Neurosurgery, University Medical Center, Goettingen, Germany. · German Parkinson Study Group, Marburg, Germany. · Department of Neurodegeneration, Hertie-Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases, Tübingen, Germany. · Department of Clinical Pharmacology and Neurosciences, NeuroToul Excellence Center for Neurodegenerative Disorders, University UPS of Toulouse III, CIC-9302/INSERM UMR825, Hôpital Purpan - Pavillon Riser, Toulouse, France. · NS PARK/FCRIN Network, France. · Department of Neurology, Philipps-University of Marburg, Marburg, Germany. · Schön Klinik München-Schwabing, München, Germany. · Sorbonne Universités, UPMC Univ Paris 06, and INSERM UMRS 1127 /CIC-1422, and CNRS UMR 7225, and AP-HP, and ICM, Hôpital Pitié-Salpêtrière, Département des maladies du système nerveux, Paris, France. · Division of Neurodegenerative Diseases, Department of Neurology, Dresden University of Technology, Dresden, Germany. · Department of Neurology, UC Davis MIND Institute, Sacramento, California, USA. · Service de Neurologie et pathologie du Mouvement, Hôpital de la Timone, Marseille Cedex, France. · Univisité Lyon 1, Hospices Civils de Lyon, Hôpital Neurologique Pierre Wertheimer, Service de Neurologie C, Lyon, France. · CNRS UMR 5229, Centre de Neurosciences Cognitives, Team Basal Ganglia, Bron, France. · Service de Neurologie et Pathologie du movement, EA 1046, CHU de Lille, Hôpital Roger Salengro, Lille, France. · Movement to Health (M2H) laboratory, Euromov, University Montpellier 1, Hôpital gui de Chauliac, Montpellier, France. · Center for Neurological Restoration, Cleveland Clinic, Cleveland, Ohio, USA. · Department of Neurology, Institute for Research and Medical Care, IROCS, Rome, Italy. · Service de Neurologie, Hôpital de Hautepierre, Strasbourg, France. · Centre Investigation Clinique Neurologie, CHU Nantes, Hôpital G&R Laennec, Nantes, France. · Service de Neurologie, Hôpital Gabriel Montpied, Clermont-Ferrand, France. · Department of Neurology, James J. and Joan A. Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati Academic Health Center, Cincinnati, Ohio, USA. · Feinstein Institute for Medical Research, North Shore - LIJ Health System, Manhasset, New York, USA. · Service de Neurologie, CIC-INSERM 1402, CHU de Poitiers, Université de Poitiers, Poitiers, France. · Klinik Haag, Haag, Germany. · Neuroscience Research Unit, Centre de recherche du CHU de Québec, Québec, Canada. · Faculty of Pharmacy, Laval University, Québec, Canada. · Novartis Institutes for BioMedical Research, Basel, Switzerland. · Biometrics Matters Ltd, Hamilton, New Zealand. · Albert Einstein College of Medicine, New York, NY, USA, and CognitionMetrics, LLC, Wilmington, Delaware, USA. · Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. · Inbiomed, San Sebastian, Spain. · CogState, Inc, New Haven, Connecticut, USA. · Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada. ·Mov Disord · Pubmed #26990766.

ABSTRACT: BACKGROUND: This phase 2 randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of the nicotinic acetylcholine receptor α7 agonist AQW051 in patients with Parkinson's disease and levodopa-induced dyskinesia. METHODS: Patients with idiopathic Parkinson's disease and moderate to severe levodopa-induced dyskinesia were randomized to AQW051 10 mg (n = 24), AQW051 50 mg (n = 24), or placebo (n = 23) once daily for 28 days. Coprimary end points were change in Modified Abnormal Involuntary Movement Scale and Unified Parkinson's Disease Rating Scale part III scores. Secondary outcomes included pharmacokinetics. RESULTS: In total, 67 patients completed the study. AQW051-treated patients experienced no significant improvements in Modified Abnormal Involuntary Movement Scale or Unified Parkinson's Disease Rating Scale part III scores by day 28. AQW051 was well tolerated; the most common adverse events were dyskinesia, fatigue, nausea, and falls. CONCLUSIONS: AQW051 did not significantly reduce dyskinesia or parkinsonian severity. © 2016 International Parkinson and Movement Disorder Society.

24 Clinical Trial Preladenant as an Adjunctive Therapy With Levodopa in Parkinson Disease: Two Randomized Clinical Trials and Lessons Learned. 2015

Hauser, Robert A / Stocchi, Fabrizio / Rascol, Olivier / Huyck, Susan B / Capece, Rachel / Ho, Tony W / Sklar, Peter / Lines, Christopher / Michelson, David / Hewitt, David. ·Parkinson's Disease and Movement Disorders Center, University of South Florida, National Parkinson Foundation Center of Excellence, Tampa. · Institute of Neurology, L'Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Rome, Italy. · Clinical Investigation Center, Institut National de la Santé et de la Récherche Médicale, Toulouse University, Toulouse, France. · Merck & Co, Inc, Kenilworth, New Jersey. ·JAMA Neurol · Pubmed #26523919.

ABSTRACT: IMPORTANCE: Preladenant is an adenosine 2A receptor antagonist that reduced "off" time in a placebo-controlled phase 2b trial in patients with Parkinson disease (PD). We sought to confirm its efficacy in phase 3 trials. OBJECTIVE: To evaluate preladenant as an adjunct to levodopa in patients with PD and motor fluctuations. DESIGN, SETTING, AND PARTICIPANTS: Two 12-week, phase 3, randomized, placebo-controlled, double-blind trials performed from July 15, 2010, to April 16, 2013. The setting included neurology clinics, clinical research centers, and hospitals in the Americas, the European Union, Eastern Europe, India, and South Africa. Participants included patients with moderate to severe PD taking levodopa who were experiencing motor fluctuations. INTERVENTIONS: In trial 1, a total of 778 eligible patients were randomized to the addition of preladenant (2 mg, 5 mg, or 10 mg twice daily), placebo, or rasagiline mesylate (1 mg/d) in a 1:1:1:1:1 ratio. In trial 2, a total of 476 eligible patients were randomized to the addition of preladenant (2 mg or 5 mg twice daily) or placebo in a 1:1:1 ratio. MAIN OUTCOMES AND MEASURES: The primary outcome measure was change in off time from baseline to week 12. RESULTS: In trial 1, neither preladenant nor rasagiline was superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.10 hour (95% CI, -0.69 to 0.46 hour) for preladenant 2 mg twice daily, -0.20 hour (95% CI, -0.75 to 0.41 hour) for preladenant 5 mg twice daily, -0.00 hour (95% CI, -0.62 to 0.53 hour) for preladenant 10 mg twice daily, and -0.30 hour (95% CI, -0.90 to 0.26 hour) for rasagiline mesylate 1 mg/d. In trial 2, preladenant was not superior to placebo in reducing off time from baseline to week 12. The differences vs placebo were -0.20 hour (95% CI, -0.72 to 0.35 hour) for preladenant 2 mg twice daily and -0.30 hour (95% CI, -0.86 to 0.21 hour) for preladenant 5 mg twice daily. Preladenant was well tolerated, with the most common adverse event that showed an increase over placebo in both trials being constipation (6%-8% for preladenant vs 1%-3% for placebo). CONCLUSIONS AND RELEVANCE: In these phase 3 trials, preladenant did not significantly reduce off time compared with placebo. That the active control rasagiline also failed to demonstrate a significant reduction in off time suggests that issues of study design or conduct may have affected these trials. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01155466 and NCT01227265.

25 Clinical Trial Long-term effects of automated mechanical peripheral stimulation on gait patterns of patients with Parkinson's disease. 2015

Stocchi, Fabrizio / Sale, Patrizio / Kleiner, Ana F R / Casali, Miriam / Cimolin, Veronica / de Pandis, Francesca / Albertini, Giorgio / Galli, Manuela. ·aDepartment of Neurorehabilitation, IRCCS San Raffaele Pisana, Rome bDepartment of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy cMovement Analysis and Neuroscience-Neurological Rehabilitation Laboratories, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, Brasil dSan Raffaele Cassino Hospital, Tosinvest Sanità, Rome, Italy. ·Int J Rehabil Res · Pubmed #26164797.

ABSTRACT: New treatments based on peripheral stimulation of the sensory-motor system have been inspiring new rehabilitation approaches in Parkinson's disease (PD), especially to reduce gait impairment, levodopa washout effects, and the incidence of falls. The aim of this study was to evaluate the change in gait and the clinical status of PD patients after six sessions of a treatment based on automated mechanical peripheral stimulation (AMPS). Eighteen patients with PD and 15 age-matched healthy individuals (control group) participated in this study. A dedicated medical device delivered the AMPS. PD patients were treated with AMPS six times once every 4 days. All PD patients were treated in the off-levodopa phase and were evaluated with gait analysis before and after the first intervention (acute phase), after the sixth intervention, 48 h after the sixth intervention, and 10 days after the end of the treatment. To compare the differences among the AMPS interventions (pre, 6 AMPS, and 10 days) in terms of clinical scales, a t-test was used (α≤0.05). In addition, to compare the differences among the AMPS interventions (pre, post, 6 AMPS, 48 h and 10 days), the gait spatiotemporal parameters were analyzed using the Friedman test and the Bonferroni post-hoc test (α≤0.05). Also, for comparisons between the PD group and the control group, the gait spatiotemporal parameters were analyzed using the Mann-Whitney test and the Bonferroni post-hoc test (α≤0.05). The results of the study indicate that the AMPS treatment has a positive effect on bradykinesia because it improves walking velocity, has a positive effect on the step and stride length, and has a positive effect on walking stability, measured by the increase in stride length. These results are consistent with the improvements measured with clinical scales. These findings indicate that AMPS treatment seems to generate a more stable walking pattern in PD patients, reducing the well-known gait impairment that is typical of PD; regular repetition every 4 days of AMPS treatment appears to be able to improve gait parameters, to restore rhythmicity, and to reduce the risk of falls, with benefits maintained up to 10 days after the last treatment. The trial was registered online at ClinicalTrials.gov (number identifier: NCT0181528).

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