Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial.
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ABSTRACT:
SUBMITTER: Espay AJ
PROVIDER: S-EPMC3068005 | biostudies-literature | 2011 Apr
REPOSITORIES: biostudies-literature
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Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial.
Espay A J AJ Dwivedi A K AK Payne M M Gaines L L Vaughan J E JE Maddux B N BN Slevin J T JT Gartner M M Sahay A A Revilla F J FJ Duker A P AP Shukla R R
Neurology 20110401 14
<h4>Background</h4>There is a paucity of therapies for gait impairment in Parkinson disease (PD). Open-label studies have suggested improved gait after treatment with methylphenidate (MPD).<h4>Objective</h4>To evaluate the efficacy of MPD for the treatment of gait impairment in PD.<h4>Methods</h4>Twenty-seven subjects with PD and moderate gait impairment were screened for this 6-month placebo-controlled, double-blind study. Subjects were randomly assigned to MPD (maximum, up to 80 mg/day) or pla ...[more]
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Project description:Background and purposeThis study presents a secondary analysis from the Progressive Resistance Exercise Training in Parkinson Disease (PRET-PD) trial investigating the effects of progressive resistance exercise (PRE) and a Parkinson disease (PD)-specific multimodal exercise program, modified Fitness Counts (mFC), on spatial, temporal, and stability-related gait impairments in people with PD.MethodsForty-eight people with PD were randomized to participate in PRE or mFC 2 times a week for 24 months; 38 completed the study. Gait velocity, stride length, cadence, and double-support time were measured under 4 walking conditions (off-/on-medication, comfortable/fast speed). Ankle strength was also measured off- and on-medication. Twenty-four healthy controls provided comparison data at one time point.ResultsAt 24 months, there were no significant differences between exercise groups. Both groups improved fast gait velocity off-medication, cadence in all conditions, and plantarflexion strength off-/on-medication. Both groups with PD had more gait measures that approximated the healthy controls at 24 months than at baseline. Plantarflexion strength was significantly associated with gait velocity and stride length in people with PD at baseline and 24 months, but changes in strength were not associated with changes in gait.Discussion and conclusionsTwenty-four months of PRE and mFC were associated with improved off-medication fast gait velocity and improved cadence in all conditions, which is important because temporal gait measures can be resistant to medications. Spatial and stability-related measures were resistant to long-term improvements, but did not decline over 24 months. Strength gains did not appear to transfer to gait.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A161).
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Project description:ImportanceThe burden of neurological disorders is increasing, but access to care is limited. Providing specialty care to patients via telemedicine could help alleviate this growing problem.ObjectiveTo evaluate the feasibility, effectiveness, and economic benefits of using web-based videoconferencing (telemedicine) to provide specialty care to patients with Parkinson disease in their homes.DesignA 7-month, 2-center, randomized controlled clinical trial.SettingPatients' homes and outpatient clinics at 2 academic medical centers.ParticipantsTwenty patients with Parkinson disease with Internet access at home.InterventionCare from a specialist delivered remotely at home or in person in the clinic.Main outcome measuresThe primary outcome variable was feasibility, as measured by the percentage of telemedicine visits completed as scheduled. Secondary outcome measures included clinical benefit, as measured by the 39-item Parkinson Disease Questionnaire, and economic value, as measured by time and travel.ResultsTwenty participants enrolled in the study and were randomly assigned to telemedicine (n = 9) or in-person care (n = 11). Of the 27 scheduled telemedicine visits, 25 (93%) were completed, and of the 33 scheduled in-person visits, 30 (91%) were completed (P = .99). In this small study, the change in quality of life did not differ for those randomly assigned to telemedicine compared with those randomly assigned to in-person care (4.0-point improvement vs 6.4-point improvement; P = .61). Compared with in-person visits, each telemedicine visit saved participants, on average, 100 miles of travel and 3 hours of time.Conclusion and relevanceUsing web-based videoconferencing to provide specialty care at home is feasible, provides value to patients, and may offer similar clinical benefit to that of in-person care. Larger studies are needed to determine whether the clinical benefits are indeed comparable to those of in-person care and whether the results observed are generalizable.Trial registrationclinicaltrials.gov Identifier: NCT01476306.
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Project description:In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease.Trial registrationClinicalTrials.gov NCT01341431.
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Project description:ImportanceThe travel required to receive deep brain stimulation (DBS) programming causes substantial burden on patients and limits who can access DBS therapy.ObjectiveTo evaluate the efficacy of home health DBS postoperative management in an effort to reduce travel burden and improve access.Design, settings, and participantsThis open-label randomized clinical trial was conducted at University of Florida Health from November 2017 to April 2020. Eligible participants had a diagnosis of Parkinson disease (PD) and were scheduled to receive DBS independently of the study. Consenting participants were randomized 1:1 to receive either standard of care or home health postoperative DBS management for 6 months after surgery. Primary caregivers, usually spouses, were also enrolled to assess caregiver strain.InterventionsThe home health postoperative management was conducted by a home health nurse who chose DBS settings with the aid of the iPad-based Mobile Application for PD DBS system. Prior to the study, the home health nurse had no experience providing DBS care.Main outcomes and measuresThe primary outcome was the number of times each patient traveled to the movement disorders clinic during the study period. Secondary outcomes included changes from baseline on the Unified Parkinson's Disease Rating Scale part III.ResultsApproximately 75 patients per year were scheduled for DBS. Of the patients who met inclusion criteria over the entire study duration, 45 either declined or were excluded for various reasons. Of the 44 patients enrolled, 19 of 21 randomized patients receiving the standard of care (mean [SD] age, 64.1 [10.0] years; 11 men) and 23 of 23 randomized patients receiving home health who underwent a minimum of 1 postoperative management visit (mean [SD] age, 65.0 [10.9] years; 13 men) were included in analysis. The primary outcome revealed that patients randomized to home health had significantly fewer clinic visits than the patients in the standard of care arm (mean [SD], 0.4 [0.8] visits vs 4.8 [0.4] visits; P < .001). We found no significant differences between the groups in the secondary outcomes measuring the efficacy of DBS. No adverse events occurred in association with the study procedure or devices.Conclusions and relevanceThis study provides evidence supporting the safety and feasibility of postoperative home health DBS management.Trial registrationClinicalTrials.gov Identifier: NCT02474459.
| S-EPMC8240011 | biostudies-literature
Project description:ObjectiveTo investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD).MethodsThe Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms.ResultsCumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 +/- 9.6 years, Hoehn-Yahr stage 1-2.5) was 2.4% (95% confidence interval: 1.2%-3.5%) at 2 years and 5.8% (3.7%-7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline.ConclusionsThe relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination-based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.
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Project description:ImportanceThere are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies.ObjectiveTo determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.Design, setting, and patientsThe Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1:1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.InterventionsParticipants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).Main outcomes and measuresThe primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes.ResultsThe trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P < .01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system.Conclusions and relevanceAmong patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease.Trial registrationclinicaltrials.gov Identifier: NCT00449865.
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Project description:ObjectiveTo compare the efficacy of treadmill exercises and stretching and resistance exercises in improving gait speed, strength, and fitness for patients with Parkinson disease.DesignA comparative, prospective, randomized, single-blinded clinical trial of 3 types of physical exercise.SettingThe Parkinson's Disease and Movement Disorders Center at the University of Maryland and the Baltimore Veterans Affairs Medical Center, Geriatric Research Education and Clinical Center.PatientsA total of 67 patients with Parkinson disease who had gait impairment were randomly assigned to 1 of 3 arms of the trial. INTERVENTIONS; (1) A higher-intensity treadmill exercise (30 minutes at 70%-80% of heart rate reserve), (2) a lower-intensity treadmill exercise (50 minutes at 40%-50% of heart rate reserve), and (3) stretching and resistance exercises (2 sets of 10 repetitions on each leg on 3 resistance machines [leg press, leg extension, and curl]). These exercises were performed 3 times a week for 3 months.Main outcome measuresThe primary outcome measures were gait speed (6-minute walk), cardiovascular fitness (peak oxygen consumption per unit time [$$ VO2], and muscle strength (1-repetition maximum strength).ResultsAll 3 types of physical exercise improved distance on the 6-minute walk: lower-intensity treadmill exercise (12% increase; P=.001), stretching and resistance exercises (9% increase; P<.02), and higher-intensity treadmill exercise (6% increase; P=.07), with no between-group differences. Both treadmill exercises improved peak $$ VO2 (7%-8% increase; P<.05) more than did the stretching and resistance exercises. Only stretching and resistance improved muscle strength (16% increase; P<.001).ConclusionsThe effects of exercise were seen across all 3 exercise groups. The lower-intensity treadmill exercise resulted in the greatest improvement in gait speed. Both the higher- and lower-intensity treadmill exercises improved cardiovascular fitness. Only the stretching and resistance exercises improved muscle strength. Therefore, exercise can improve gait speed, muscle strength, and fitness for patients with Parkinson disease. The combination of treadmill and resistance exercises may result in greater benefit and requires further investigation.
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Project description:ImportanceThere is a critical need for careful and independent validation of reported symptomatic efficacy and dopaminergic biomarker changes induced by nilotinib in Parkinson disease (PD).ObjectivesTo assess safety and tolerability of nilotinib in participants with moderately advanced PD. Secondary and exploratory objectives were to assess its affect on PD disability, pharmacokinetics, cerebrospinal fluid (CSF) penetration, and biomarkers.Design, setting, and participantsThis was a 6-month, multicenter, randomized parallel-group, double-blind, placebo-controlled trial. Recruitment was from November 20, 2017, to December 28, 2018, and follow-up ended on September 9, 2019. The study was conducted at 25 US sites. The study approached 173 patients, of whom 48 declined, 125 were screened, and 76 who received a stable regimen of PD medications were enrolled (39% screen failure).InterventionsParticipants were randomized 1:1:1 to placebo, 150-mg nilotinib, or 300-mg nilotinib once daily orally for 6 months, followed by 2-month off-drug evaluation.Main outcomes and measuresThe primary outcomes were safety and tolerability. The tolerability end point was defined as the ability to complete the study while receiving the assigned dose. An active arm was considered tolerable if the percentage of participants meeting the tolerability end point for that group was not significantly lower than the percentage observed in the placebo group. Secondary outcomes included change in PD disability (Movement Disorder Society Unified Parkinson's Disease Rating Scale [MDS-UPDRS], Part II OFF/ON). Exploratory outcomes included serum and CSF pharmacokinetic profile, and CSF dopaminergic biomarkers.ResultsAt baseline, mean (SD) participants' age was 64.6 (7.5) years, 52 were male (68%), mean (SD) disease duration was 9.9 years (4.7), MDS-UPDRS Part 1-3 OFF score was 66.4 (19.3), ON score was 48.4 (16.2), and Montreal Cognitive Assessment score was 27.1 (2.2). The number of participants who completed the study receiving the assigned dose were 21 (84%), 19 (76%), and 20 (77%) in the placebo, 150-mg, and 300-mg arms, respectively. Both active doses had acceptable safety profile. The most common reasons for drug suspension were asymptomatic, dose-dependent elevations of amylase, and/or lipase. Nilotinib, 150 mg and 300 mg, exhibited worse MDS-UPDRS-3 ON scores compared with placebo, achieving significance for nilotinib, 300 mg, at month 1 (P < .01). There was no difference in the change of MDS-UPDRS-3 OFF from baseline to 6 months between groups (P = .17). Cerebrospinal fluid/serum ratio of nilotinib concentration was 0.2% to 0.3%. There was no evidence of treatment-related alteration of dopamine metabolites in the CSF.Conclusions and relevanceWhile we demonstrated acceptable safety and tolerability of nilotinib in our cohort, the low CSF exposure and lack of biomarkers effect combined with the efficacy data trending in the negative direction indicate that nilotinib should not be further tested in PD.Trial registrationClinicalTrials.gov Identifier: NCT03205488.
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Project description:Background: To evaluate the efficacy, safety and tolerability of methylphenidate (MPH) for cognitive function in older patients with mild cognitive impairment (MCI). Methods: Male and female subjects aged 65 years and older with a clinical diagnosis MCI were included in an exploratory randomized, double-blind, placebo-controlled trial. Eligible subjects were assigned to either treatment with immediate-release MPH or placebo. The active compound was administered in an increasing-dose stepwise fashion, namely 10 mg MPH on day 1, 20 mg on day 2, and 30 mg on day 3. Subjects remained under observation for 4 h following drug administration and were monitored for changes in blood pressure and for adverse events. Cognitive outcome measures included the Montreal Cognitive Assessment (MoCA) and the Neurotrax Mindstreams computerized cognitive assessment battery. Results: Of 17 subjects enrolled, 15 subjects completed the study, 7 in the active MPH group and 8 in the placebo group. The average age of the participants was 76.1 ± 6.6 years and 10 (66.7%) were men. Following the final dose a significant benefit on memory (predominantly non-verbal memory) was found in the MPH group. While 12 adverse events were reported, they were all rated as mild to moderate. Conclusions: Our finding of modest beneficial effects of MPH on memory tests in older subjects with MCI in this exploratory study is of interest and should be investigated in further studies.
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Project description:ImportanceCurrent treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy.ObjectiveTo determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD.Design, setting, and participantsThis randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021.InterventionsParticipants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period.Main outcomes and measuresThe prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event.ResultsOf 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE.Conclusions and relevanceIn this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial.Trial registrationISRCTN Identifier: 16108482.
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