Self‐management rehabilitation and health‐related quality of life in Parkinson's disease: A randomized controlled trial

The purpose of this randomized controlled trial was to determine whether increasing hours of self‐management rehabilitation had increasing benefits for health‐related quality of life (HRQOL) in Parkinson's disease beyond best medical treatment, whether effects persisted at 2 and 6 months of follow‐up, and whether targeted compared with nontargeted HRQOL domains responded more to rehabilitation. Participants on best medication therapy were randomly assigned to one of three conditions for 6 weeks intervention: 0 hours of rehabilitation; 18 hours of clinic group rehabilitation plus 9 hours of attention control social sessions; and 27 hours of rehabilitation, with 18 in clinic group rehabilitation and 9 hours of rehabilitation designed to transfer clinic training into home and community routines. Results (N = 116) showed that at 6 weeks, there was a beneficial effect of increased rehabilitation hours on HRQOL measured with the Parkinson's Disease Questionnaire‐39 summary index (F(1,112) = 6.48, η = 0.23, CI = 0.05–0.40, P = 0.01). Benefits persisted at follow‐up. The difference between 18 and 27 hours was not significant. Clinically relevant improvement occurred at a greater rate for 18 and 27 hours (54% improved) than for 0 hours (18% improved), a significant 36% difference in rates (95% CI = 20–52% difference). Effects were largest in two targeted domains: communication and mobility. More concerns with mobility and activities of daily living at baseline predicted more benefit from rehabilitation. © 2010 Movement Disorder Society     

Twice‐daily,low‐dose pramipexole in early Parkinson's disease: A randomized,placebo‐controlled trial

To compare the safety and efficacy of low dosages of pramipexole given twice daily (bid) in early Parkinson's disease (PD) with those of a standard 3 times daily (tid) regimen in a randomized, double‐blind, placebo controlled trial involving 311 early PD patients not receiving dopaminergic treatment. Subjects were randomly assigned and followed on assigned treatment for 12 weeks with pramipexole at dosages of 0.5 mg bid, 0.75 mg bid, or 0.5 mg tid, or matching placebo. All subjects were dosed 3 times daily, with placebo if necessary, to maintain blinding. The primary outcome was the change from baseline to Week 12 in the Unified Parkinson Disease Rating Scale (UPDRS) total score (Parts I–III). All active dosages had similar antiparkinson efficacy showing reductions of 4–5 UPDRS points relative to placebo (p < 0.0001) for each comparison. Somnolence, fatigue, nausea, constipation, and peripheral edema were more common in the active treatment groups than in the placebo group, but their frequency did not vary by dosage. In this fixed dosage, randomized study pramipexole administered twice daily at a total daily dosage of 1.0–1.5 mg daily was of comparable efficacy and tolerability to a dosage of 0.5 mg tid over a 12‐week treatment period in early PD. © 2010 Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial evaluating cysteamine in Huntington's disease

Background : Cysteamine has been demonstrated as potentially effective in numerous animal models of Huntington's disease. Methods : Ninety‐six patients with early‐stage Huntington's disease were randomized to 1200 mg delayed‐release cysteamine bitartrate or placebo daily for 18 months. The primary end point was the change from baseline in the UHDRS Total Motor Score. A linear mixed‐effects model for repeated measures was used to assess treatment effect, expressed as the least‐squares mean difference of cysteamine minus placebo, with negative values indicating less deterioration relative to placebo. Results : At 18 months, the treatment effect was not statistically significant — least‐squares mean difference, ‐1.5 ± 1.71 (P = 0.385) — although this did represent less mean deterioration from baseline for the treated group relative to placebo. Treatment with cysteamine was safe and well tolerated. Conclusions : Efficacy of cysteamine was not demonstrated in this study population of patients with Huntington's disease. Post hoc analyses indicate the need for definitive future studies. © 2017 International Parkinson and Movement Disorder Society     

Comparison of desipramine and citalopram treatments for depression in Parkinson's disease: A double‐blind,randomized, placebo‐controlled study

Depression is one of the most common psychiatric disturbances in Parkinson's disease (PD). Recent reviews have highlighted the lack of controlled trials and the ensuing difficulty in formulating recommendations for antidepressant use in PD. We sought to establish whether antidepressants provide real benefits and whether tricyclic and selective serotonin reuptake inhibitor (SSRI) antidepressants differ in their short‐term efficacy, because the time to onset of therapeutic benefit remains an important criterion in depression. The short‐term efficacy (after 14 and 30 days) of two antidepressants (desipramine, a predominantly noradrenergic reuptake inhibitor tricyclic and citalopram, a SSRI) was assessed in a double‐blind, randomized, placebo‐ controlled study of 48 nondemented PD patients suffering from major depression. After 14 days, desipramine prompted an improvement in the Montgomery Asberg Depression Rating Scale (MADRS) score, compared with citalopram and placebo. Both antidepressants produced significant improvements in the MADRS score after 30 days. Mild adverse events were twice as frequent in the desipramine group as in the other groups. A predominantly noradrenergic tricyclic antidepressant induced a more intense short‐term effect on parkinsonian depression than did an SSRI. However, desipramine's lower tolerability may outweigh its slight short‐term clinical advantage. © 2008 Movement Disorder Society     

The impact of left prefrontal repetitive transcranial magnetic stimulation on depression in Parkinson's disease: A randomized,double‐blind,placebo‐controlled study

Based on several open‐label and case studies, repetitive transcranial magnetic stimulation (rTMS) seems to have an antidepressive effect on patients with Parkinson's disease (PD). However, this hypothesis requires further confirmation. We conducted a randomized, double‐blind placebo‐controlled study to evaluate the effect of rTMS over the left dorsolateral prefrontal cortex (DLPFC) on depression and various motor and nonmotor features of PD. Twenty‐two PD patients with mild or moderate depressive episodes were assigned into two groups, one receiving real‐rTMS (90% of resting motor threshold, 5 Hz, 600 pulses‐a‐day for 10 days) over the left DLPFC, and another group receiving sham‐rTMS. An investigator blinded to the treatment performed three video‐taped examinations on each patient: before stimulation (baseline), 1 day (short term), and 30 days after treatment session ended (long‐term effect). Mini‐Mental State Examination, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn‐Yahr, Epworth Sleepiness, Visual Analog and Montgomery‐Asberg Depression Rating Scales (MADRS), Beck Depression Inventory (BDI), and Trail making and Stroop tests were applied. In the actively treated group, not only depression rating scales showed significant improvement 30 days after treatment ended (BDI by 44.4% and MADRS by 26.1%), but also the accuracy of Stroop test (by 16%). We could also demonstrate an insignificant improvement in UPDRS‐III by 7.5 points (31.9%, P = 0.06). In the sham‐treated group none of the examined tests and scales improved significantly after sham stimulation. Our study demonstrated the beneficial effect of the left DLPFC rTMS on depression in PD lasting at least 30 days after treatment. However, this result should be confirmed in patients with severe depression by further clinical trials. © 2010 Movement Disorder Society     

A randomized,double‐blind,placebo‐controlled trial of pridopidine in Huntington's disease

We examined the effects of 3 dosages of pridopidine, a dopamine‐stabilizing compound, on motor function and other features of Huntington's disease, with additional evaluation of its safety and tolerability. This was a randomized, double‐blind, placebo‐controlled trial in outpatient neurology clinics at 27 sites in the United States and Canada. Two hundred twenty‐seven subjects enrolled from October 24, 2009, to May 10, 2010. The intervention was pridopidine, either 20 (n=56), 45 (n=55), or 90 (n=58) mg daily for 12 weeks or matching placebo (n=58). The primary outcome measure was the change from baseline to week 12 in the Modified Motor Score, a subset of the Unified Huntington's Disease Rating Scale Total Motor Score. Measures of safety and tolerability included adverse events and trial completion on the assigned dosage. After 12 weeks, the treatment effect (relative to placebo, where negative values indicate improvement) of pridopidine 90 mg/day on the Modified Motor Score was ?1.2 points (95% confidence interval [CI], ?2.5 to 0.1 points; P = .08). The effect on the Total Motor Score was ?2.8 points (95% CI, ?5.4 to ?0.1 points; nominal P = .04). No significant effects were seen in secondary outcome measures with any of the active dosages. Pridopidine was generally well tolerated. Although the primary analysis did not demonstrate a statistically significant treatment effect, the overall results suggest that pridopidine may improve motor function in Huntington's disease. The 90 mg/day dosage appears worthy of further study. Pridopidine was well tolerated. © 2013 International Parkinson and Movement Disorder Society     

Entacapone to tolcapone switch: Multicenter double‐blind,randomized, active‐controlled trial in advanced Parkinson's disease

This double‐blind study examined the efficacy and safety of replacing entacapone with tolcapone in fluctuating Parkinson's disease (PD) patients. Patients receiving entacapone for ≥15 days were randomly assigned to continue entacapone (n = 75) or switch to tolcapone (n = 75) and were followed up for 3 weeks. Efficacy measures included changes in on time (without disabling dyskinesia) and an investigator's global assessment (IGA). The on time increased by ≥1 hour/day (primary efficacy measure) in 43% of entacapone‐treated patients and 53% of tolcapone‐treated patients, and by ≥3 hours/day in 13% and 25%, respectively. The IGA indicated moderate/marked improvements in 25% of entacapone patients and 39% receiving tolcapone. Response rates (the proportion of patients with ≥1 hour/day increase in on time and improvements on IGA) were 17% with entacapone and 32% with tolcapone. Dyskinesia was the most common adverse event affecting 29% of entacapone and 31% of tolcapone recipients. One patient in each group had elevated liver enzymes, resulting in treatment withdrawal (levels returned to normal thereafter in both cases). In conclusion, within the limits of the protocol, there was a tendency for tolcapone to offer enhanced efficacy in patients with fluctuating PD, despite optimized entacapone therapy. Tolcapone can be considered, therefore, for patients whose motor fluctuations are inadequately controlled by their existing regimen. © 2006 Movement Disorder Society     

Pardoprunox in early Parkinson's disease: Results from 2 large,randomized double‐blind trials

This report presents the results of 2 randomized trials—Rembrandt and Vermeer—on the efficacy and safety of pardoprunox in patients with early Parkinson's disease. Patients with Parkinson's disease with a Unified Parkinson's Disease Rating Scale–Motor score ≥ 10 and modified Hoehn and Yahr stage ≤ 3 were randomized to pardoprunox (fixed doses of 6 mg/day [n = 115] or 12 mg/day [n = 118] or a flexible‐dose range of 12–42 mg/day [n = 116]) or placebo (n = 119) in Rembrandt and pardoprunox 12–42 mg/day (n = 108), pramipexole 1.5–4.5 mg/day (n = 116), or placebo (n = 110) in Vermeer. Pardoprunox showed a significant benefit over placebo in the primary efficacy variable, least‐square mean change from baseline in Unified Parkinson's Disease Rating Scale–Motor score: Rembrandt—fixed doses of 6 and 12 mg/day, ?6.0 and ?4.7 points, respectively; flexible‐dose 12–42 mg/day, ?5.5 points; placebo, ?2.9 points; Vermeer—flexible‐dose 12–42 mg/day, ?4.9 points; placebo, ?2.5 points; pramipexole, ?5.7 points. No minimum effective dose was established. Secondary efficacy parameters supported the results of the primary efficacy variable. Pardoprunox tolerability was dose related: flexible‐dose 12–42 mg/day showed the highest dropout rate due to treatment‐emergent adverse events (Rembrandt, 56.0%; Vermeer, 46.3%) and overall incidence of treatment‐emergent adverse events (Rembrandt, 97.4%; Vermeer, 92.6%), primarily due to nausea, somnolence, and dizziness. Because pardoprunox showed similar efficacy across all dose groups, these observations suggest that the 12–42 mg/day dose range was higher than therapeutically required. Furthermore, the early onset of treatment‐emergent adverse events and dropouts observed for pardoprunox suggest that titration was too rapid. Pardoprunox significantly improved motor symptoms in patients with early Parkinson's disease, but further investigation into the dose and titration schedule is required to improve tolerability. © 2011 Movement Disorder Society     

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: A randomized,double‐blind,placebo‐controlled,multicenter study

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type‐B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double‐blind, placebo‐controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty‐five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span–backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit‐ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type‐B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment. © 2011 Movement Disorder Society     

Macrogol for the treatment of constipation in Parkinson's disease. A randomized placebo‐controlled study

Chronic constipation is the most frequent symptom of autonomic system involvement in Parkinson's disease (PD). Quite often the symptom is severe and impairs patients' quality of life. The objective of this study is to determine the efficacy and safety of an isosmotic macrogol solution for the treatment of constipation in PD patients, in a double‐blind, placebo‐controlled study. A total of 57 PD patients with constipation were randomly assigned to receive an isosmotic macrogol electrolyte solution (MC‐ES; 29 patients) or placebo (28 patients) for 8 weeks. Treatment efficacy was defined as complete relief of the symptom or a marked improvement of two of the following indicators: stool frequency, straining, stool consistency, use of rectal laxatives as a rescue therapy. The responder rates were significantly higher in the MC‐ES group both at the first (4 weeks; P < 0.0003) and at the final evaluation (8 weeks; P < 0.0012). The frequency of bowel movements (P < 0.002) and stool consistency (P < 0.006) were significantly changed in the MC‐ES group compared to the placebo group. At the final evaluation, a rectal laxative was used by 2 (12.5%) patients on placebo, whereas no use was recorded in the MC‐ES group. Responder rate for straining showed a favorable trend in patients treated with macrogol versus placebo. Unified Parkinson's Disease Rating Scale Part III and Parkinson's Disease Questionnaire (PDQ‐39) did not show any significant modification in either group during the 8‐week treatment period. The results of this placebo‐controlled study show the efficacy of MC‐ES in the treatment of constipation in PD. MC‐ES was well‐tolerated and did not affect the course of PD. © 2006 Movement Disorder Society     

Randomized trial of IPX066, carbidopa/levodopa extended release,in early Parkinson's disease

ObjectiveIPX066 is an extended release carbidopa/levodopa formulation designed to rapidly attain and maintain therapeutic plasma concentrations for a prolonged duration, allowing dosing intervals of approximately 6 h. The objective was to assess the efficacy, safety, and impact on quality of life of IPX066 in the treatment of levodopa-naive Parkinson's disease (PD) patients.MethodsThis was a randomized, double-blind, placebo-controlled, 30-week study of 381 levodopa-naïve patients assigned to placebo or IPX066 containing 145, 245 or 390 mg of levodopa administered three times daily (TID). The primary efficacy measure was change from Baseline in Unified Parkinson's Disease Rating Scale (UPDRS) activities of daily living (Part II) + motor scores (Part III), at 30 weeks. Secondary outcome measures included UPDRS total and subscores, patient and clinician global impressions (PGI-I, CGI-I), and the Parkinson's Disease Questionnaire (PDQ-39).ResultsAll IPX066 dosages were superior to placebo throughout the study and at 30 weeks (P < 0.0001). The mean improvement in UPDRS Parts II + III at 30 weeks compared to baseline was 11.7, 12.9, and 14.9 points for the three dosages and 0.6 points for placebo (P < 0.0001, all dosages). PDQ-39 total scores improved with IPX066 (P ≤ 0.034, all dosages). The most commonly reported adverse events with IPX066 included nausea, dizziness, and headache. No unexpected drug-related serious adverse events were reported.ConclusionIPX066 provided significant clinical benefits at the three dosages tested compared to placebo and was well tolerated in levodopa-naive PD patients. Of the dosages tested, IPX066 145 mg TID appeared to provide the best overall balance between efficacy and safety.     

A two‐year randomized controlled trial of progressive resistance exercise for Parkinson's disease

The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson's disease have not been studied in controlled trials. The objective of the current trial was to compare 6‐, 12‐, 18‐, and 24‐month outcomes of patients with Parkinson's disease who received PRE with a stretching, balance, and strengthening exercise program. The authors conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients matched by sex and off‐medication scores on the Unified Parkinson's Disease Rating Scale, motor subscale (UPDRS‐III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight‐lifting program. The modified fitness counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised 2 days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first 6 months and 1 weekly session after 6 months. The primary outcome was the off‐medication UPDRS‐III score. Patients were followed for 24 months at 6‐month intervals. Of 51 patients, 20 in the PRE group and 18 in the mFC group completed the trial. At 24 months, the mean off‐medication UPDRS‐III score decreased more with PRE than with mFC (mean difference, ?7.3 points; 95% confidence interval, ?11.3 to ?3.6; P<0.001). The PRE group had 10 adverse events, and the mFC group had 7 adverse events. PRE demonstrated a statistically and clinically significant reduction in UPDRS‐III scores compared with mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs. © 2013 Movement Disorder Society     

Increasing access to specialty care: A pilot,randomized controlled trial of telemedicine for Parkinson's disease

We conducted a randomized, controlled pilot trial to evaluate the feasibility of providing subspecialty care via telemedicine for patients with Parkinson's disease residing in a remote community located ～130 miles from an academic movement disorders clinic. Study participants were randomized to receive telemedicine care with a movement disorder specialist at the University of Rochester or to receive their usual care. Participants in the telemedicine group received three telemedicine visits over six months. Feasibility, as measured by the completion of telemedicine visits, was the primary outcome measure. Secondary measures were quality of life, patient satisfaction, and clinical outcomes. Ten participants residing in the community were randomized to receive telemedicine care (n = 6) or their usual care (n = 4). Four nursing home patients were assigned to telemedicine. Those receiving telemedicine completed 97% (29 of 30) of their telemedicine visits as scheduled. At the study's conclusion, 13 of 14 study participants opted to receive specialty care via telemedicine. Compared with usual care, those randomized to telemedicine had significant improvements in quality of life (3.4 point improvement vs. 10.3 point worsening on the Parkinson's Disease Questionnaire 39; P = 0.04) and motor performance (0.3 point improvement vs. 6.5 point worsening on the Unified Parkinson's Disease Rating Scale, motor subscale; P = 0.03). Relative to baseline, nursing home patients experienced trends toward improvement in quality of life and patient satisfaction. Providing subspecialty care via telemedicine for individuals with Parkinson's disease living remotely is feasible. © 2010 Movement Disorder Society