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Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial.

ABSTRACT: Background:Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD). Objective:To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD. Design:Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842). Setting:57 Parkinson Study Group sites in North America. Participants:Patients with early-stage PD (duration <3 years) who were not taking dopaminergic medications at enrollment. Intervention:5 mg of immediate-release isradipine twice daily or placebo for 36 months. Measurements:The primary outcome was change in the Unified Parkinson's Disease Rating Scale (UPDRS) parts I to III score measured in the antiparkinson medication "ON" state between baseline and 36 months. Secondary outcomes included time to initiation and use of antiparkinson medications, time to onset of motor complications, change in nonmotor disability, and quality-of-life measures. Results:336 patients were randomly assigned (mean age, 62 years [SD, 9]; 68% men; disease duration, 0.9 year [SD, 0.7]; mean UPDRS part I to III score, 23.1 [SD, 8.6]); 95% of patients completed the study. Adjusted least-squares mean changes in total UPDRS score in the antiparkinson medication ON state over 36 months for isradipine and placebo recipients were 2.99 (95% CI, 0.95 to 5.03) points versus 3.26 (CI, 1.25 to 5.26) points, respectively, with a treatment effect of -0.27 (CI, -3.02 to 2.48) point (P = 0.85). Statistical adjustment for antiparkinson medication use did not change the findings. Secondary outcomes showed no effect of isradipine treatment. The most common adverse effects of isradipine were edema and dizziness. Limitation:The isradipine dose may have been insufficient to engage the target calcium channels associated with neuroprotective effects. Conclusion:Long-term treatment with immediate-release isradipine did not slow the clinical progression of early-stage PD. Primary Funding Source:National Institute of Neurological Disorders and Stroke.

SUBMITTER: Parkinson Study Group STEADY-PD III Investigators

PROVIDER: S-EPMC7465126 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial.

Annals of internal medicine 20200331 9

<h4>Background</h4>Studies suggest that dihydropyridine calcium-channel blockers may be associated with reduced risk for Parkinson disease (PD).<h4>Objective</h4>To assess the effect of isradipine, a dihydropyridine calcium-channel blocker, on the rate of clinical progression of PD.<h4>Design</h4>Multicenter, randomized, parallel-group, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT02168842).<h4>Setting</h4>57 Parkinson Study Group sites in North America.<h4>Participants</h4>Pa ...[more]

PMID: 32227247

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Project description:Background: Given the immense burden of the widespread use of opioids around the world, exploring treatments that improve drug use outcomes, and craving and withdrawal measures in individuals with opioid use disorder is crucial. This pilot study examined the feasibility and preliminary efficacy of the L-type calcium-channel blocker isradipine (ISR) to improve drug use outcomes, and craving and withdrawal measures during buprenorphine (BUP)/ISR stabilization and subsequent taper in opioid-dependent individuals.Methods: Participants were stabilized on BUP sublingual tablets within the first 2 days of week 1, were then randomized and inducted on either ISR or placebo, gradually increasing the dose over the next 2 weeks, followed by a 10-day BUP taper during weeks 5-6, and ISR/placebo taper during weeks 7 to 8. Assessments included thrice-weekly measures of craving and withdrawal, as well as vital signs and urine drug screens. Medication compliance was assessed by monitoring number of missed clinic visit days.Results: Baseline characteristics of participants (n?=?25; 60% male, 96% Caucasian, 48% employed, mean age 32.8?years) did not differ significantly between treatment groups (isradipine, n?=?11; placebo, n?=?14). During the stabilization phase (n?=?19), ISR participants had significantly lower rates of illicit opioid-positive urines (treatment × visit: t?=?-2.16, P?=?0.03), as well as reduction in craving intensity (t?=?-2.50, P?=?0.01), frequency (t?=?-3.43, P?<?0.01) and duration (t?=?-2.51, P?=?0.01). ISR was well tolerated with mild adverse effects.Conclusions: This study was likely underpowered due to being a pilot trial. Although preliminary results suggest ISR may improve BUP-assisted treatment outcomes, concerns about high number of exclusions (n?=?11 during taper phase) based on cardiovascular measures as well as ISR-induced changes in vital signs with the immediate release formulation may limit the feasibility of this approach.Trial registration: Clinicaltrials.gov identifier NCT01895270. Registered 10 July 2013, https://clinicaltrials.gov/ct2/show/NCT01895270?id=NCT01895270&draw=2&rank=1.

Project description:BackgroundExercise confers short-term benefits for individuals with Parkinson disease (PD).ObjectiveThe purpose of the study was to compare short- and long-term responses among 2 supervised exercise programs and a home-based control exercise program.DesignThe 16-month randomized controlled exercise intervention investigated 3 exercise approaches: flexibility/balance/function exercise (FBF), supervised aerobic exercise (AE), and home-based exercise (control).SettingThis study was conducted in outpatient clinics.PatientsThe participants were 121 individuals with PD (Hoehn & Yahr stages 1-3).InterventionsThe FBF program (individualized spinal and extremity flexibility exercises followed by group balance/functional training) was supervised by a physical therapist. The AE program (using a treadmill, bike, or elliptical trainer) was supervised by an exercise trainer. Supervision was provided 3 days per week for 4 months, and then monthly (16 months total). The control group participants exercised at home using the National Parkinson Foundation Fitness Counts program, with 1 supervised, clinic-based group session per month.MeasurementsOutcomes, obtained by blinded assessors, were determined at 4, 10, and 16 months. The primary outcome measures were overall physical function (Continuous Scale-Physical Functional Performance [CS-PFP]), balance (Functional Reach Test [FRT]), and walking economy (oxygen uptake [mL/kg/min]). Secondary outcome measures were symptom severity (Unified Parkinson's Disease Rating Scale [UPDRS] activities of daily living [ADL] and motor subscales) and quality of life (39-item Parkinson's Disease Quality of Life Scale [PDQ-39]).ResultsOf the 121 participants, 86.8%, 82.6%, and 79.3% completed 4, 10, and 16 months, respectively, of the intervention. At 4 months, improvement in CS-PFP scores was greater in the FBF group than in the control group (mean difference=4.3, 95% confidence interval [CI]=1.2 to 7.3) and the AE group (mean difference=3.1, 95% CI=0.0 to 6.2). Balance was not different among groups at any time point. Walking economy improved in the AE group compared with the FBF group at 4 months (mean difference=-1.2, 95% CI=-1.9 to -0.5), 10 months (mean difference=-1.2, 95% CI=-1.9 to -0.5), and 16 months (mean difference=-1.7, 95% CI=-2.5 to -1.0). The only secondary outcome that showed significant differences was UPDRS ADL subscale scores: the FBF group performed better than the control group at 4 months (mean difference=-1.47, 95% CI=-2.79 to -0.15) and 16 months (mean difference=-1.95, 95% CI=-3.84 to -0.08).LimitationsAbsence of a non-exercise control group was a limitation of the study.ConclusionsFindings demonstrated overall functional benefits at 4 months in the FBF group and improved walking economy (up to 16 months) in the AE group.

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Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial.

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Isradipine Versus Placebo in Early Parkinson Disease: A Randomized Trial.

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