scholarly journals Safety and Tolerability, Dose-Escalating, Double-Blind Trial of Oral Mannitol in Parkinson's Disease

2022 ◽  
Vol 12 ◽  
Author(s):  
Eduard Linetsky ◽  
Suaad Abd Elhadi ◽  
Max Bauer ◽  
Akiva Gallant ◽  
Montaser Namnah ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Gastrointestinal Symptoms ◽  
Secondary Outcome ◽  
Maximal Dose ◽  
Double Blind ◽  
Efficacy Measures ◽  
Dose Escalating

Mannitol, a natural alcoholic-sugar, was recently suggested as a potential disease-modifying agent in Parkinson's disease. In animal models of the disease, mannitol interferes with the formation of α-synuclein fibrils, inhibits the formation of α-synuclein oligomers and leads to phenotypic recovery of impaired motor functions. Parkinson's patients who consume mannitol report improvements of both motor and non-motor symptoms. Safety of long-term use of oral mannitol, tolerable dose and possible benefit, however, were never clinically studied. We studied the safety of oral mannitol in Parkinson's disease and assessed the maximal tolerable oral dose by conducting a phase IIa, randomized, double-blind, placebo-controlled, single-center, dose-escalating study (ClinicalTrials.gov Identifier: NCT03823638). The study lasted 36 weeks and included four dose escalations of oral mannitol or dextrose to a maximal dose of 18 g per day. The primary outcome was the safety of oral mannitol, as assessed by the number of adverse events and abnormal laboratory results. Clinical and biochemical efficacy measures were collected but were not statistically-powered. Fourteen patients receiving mannitol completed the trial (in addition to eight patients on placebo). Mannitol-related severe adverse events were not observed. Gastrointestinal symptoms limited dose escalation in 6/14 participants on mannitol. None of the clinical or biochemical efficacy secondary outcome measures significantly differed between groups. We concluded that long-term use of 18 g per day of oral mannitol is safe in Parkinson's disease patients but only two third of patients tolerate this maximal dose. These findings should be considered in the design of future efficacy trials.

scholarly journals Long-term safety and efficacy of opicapone in Japanese Parkinson’s patients with motor fluctuations

2021 ◽  
Author(s):  
Atsushi Takeda ◽  
Ryosuke Takahashi ◽  
Yoshio Tsuboi ◽  
Masahiro Nomoto ◽  
Tetsuya Maeda ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Adverse Events ◽  
Motor Fluctuations ◽  
Open Label ◽  
Double Blind ◽  
Safety And Efficacy ◽  
Open Label Extension ◽  
Off Time

AbstractThe double-blind part of the COMFORT-PD (COMt-inhibitor Findings from Opicapone Repeated Treatment for Parkinson’s Disease) study in Japanese levodopa-treated patients with Parkinson’s disease and motor fluctuations found that both opicapone 25 and 50 mg were significantly more effective than placebo. This 52-week open-label extension study evaluated the long-term safety and efficacy of opicapone 50 mg tablets in patients who completed the double-blind part of the COMFORT-PD study. Safety was monitored via adverse events, laboratory testing, and physical, cardiovascular and neurological examinations. Efficacy was primarily assessed by change in OFF-time. Secondary efficacy measures included: ON-time, percentage of OFF/ON-time responders, other outcomes from the double-blind part. 391/437 patients were transferred to the open-label extension period and included in the safety analysis set (full analysis set, n = 387; open-label completers, n = 316). Adverse events were frequently reported (n = 338, 86.4%), but < 50% were considered drug-related (39.9%) and few were considered serious (2.6%) or led to discontinuation (2.8%). Decreased OFF-time was consistently observed over the open-label period regardless of initial randomization. Change [LSM (SE)] in OFF-time from the open-label baseline to the last visit showed a persistent effect in patients initially randomized to opicapone 25 mg [− 0.37 (0.20) h, P = 0.0689] and opicapone 50 mg [− 0.07 (0.21) h, P = 0.6913] whereas opicapone 50 mg led to a statistically significant reduction in the previous placebo group [− 1.26 (0.19) h, P < 0.05]. Once-daily opicapone 50 mg was generally well tolerated and consistently reduced OFF-time over 52 weeks in Japanese levodopa-treated patients with motor fluctuations.Trial registration JapicCTI-153112; date of registration: December 25, 2015.

Selegiline as the primary treatment of Parkinson's disease - a long-term double-blind study

1997 ◽  
Vol 95 (4) ◽  
pp. 211-218 ◽  
Author(s):  
V. V. Myllylä ◽  
K. A. Sotaniemi ◽  
P. Hakulinen ◽  
O. Mäki-lkola ◽  
E. H. Heinonen
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Primary Treatment ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind

scholarly journals Low dose niacin versus placebo in the treatment of Parkinson’s Disease:  A Randomized Controlled Trial

2021 ◽  
Author(s):  
Chandramohan Wakade ◽  
Raymond Chong ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Banabihari Giri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Open Label ◽  
Double Blind ◽  
One Year ◽  
Time Point

Abstract BackgroundParkinson’s Disease (PD) patients have lower niacin levels compared to their spouses. The main objective was to study low-dose daily niacin supplementation versus placebo on motor symptoms in Parkinson’s disease subjects.MethodsA randomized, placebo-controlled, double-blind, single-center clinical trial in Parkinson’s disease patients was performed in Augusta, GA, between September 2016 to September 2019. Randomized participants were 47 PD patients who received either low-dose niacin (N = 21 ) or placebo (N = 26) for the first six months (mean age 68.4 SD, 8.7; mean duration of disease 5.8 SD 4.9; H&Y scores between 0.5 to 4; 64% subjects were Veterans). The Veterans Affairs Pharmacy generated the randomized sequence. After the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, six months, and one year of treatment. The main outcome measure was the Unified Parkinson’s Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue.Results39 subjects were analyzed with low-dose niacin (N = 18) and placebo (N = 21) for the completion of the first six months (randomized, double-blind), and 31 subjects were analyzed for the completion of the next six months (open-label) with low-dose niacin (N = 14) and placebo (N = 17). Niacin treatment was not tolerated by two subjects. The baseline mean UPDRS III score was 21.3 ± 15.8 for the niacin group and 22.4 ± 11.8 for placebo. The change with six months of placebo was 0.05 [95% CI, -2.4 to 2.32], and niacin was 1.06 [95% CI, -3.68 to 1.57]. From six to twelve months, the average UPDRS III score decreased for the placebo group by 4.58 [95% CI, -0.85 to 8.30] and the niacin group by 4.63 [95% CI, 1.42 to 7.83]. Eight subjects withdrew from the study before the 6-month time point and eight more before the one-year time point due to voluntary discontinuation, flushing, or inability to continue (SARS-CoV-2 shut-down).ConclusionLow-dose niacin supplementation may be helpful as an adjunct therapy in improving motor function in PD.Trial registrationClinicaltrials.gov, NCT03462680. Registered 12 March 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03462680?term=gpr109A&draw=2&rank=1

scholarly journals Low Dose Niacin Versus Placebo Treatment for Parkinson's Disease: A Randomized Controlled Trial

2021 ◽  
Author(s):  
Chandramohan Wakade ◽  
Raymond Chong ◽  
Marissa Seamon ◽  
Sharad Purohit ◽  
Bababihari Giri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Low Dose ◽  
Rating Scale ◽  
Controlled Trial ◽  
Secondary Outcome ◽  
Double Blind Study ◽  
Double Blind ◽  
One Year ◽  
Time Point

Abstract Background Parkinson's Disease (PD) patients have lower niacin levels compared to their spouses. The main objective was to study low-dose daily niacin supplementation on motor symptoms in Parkinson's disease subjects. Methods Forty-Seven PD patients were randomly assigned to receive low-dose niacin or placebo in a randomized, double-blind study for the first six months. After the double-blind phase, all participants received open-label niacin for the next six months. All patients were evaluated at baseline, six months, and one year of treatment. The main outcome measure was the Unified Parkinson's Disease Rating Scale III (UPDRS III) scores. Secondary outcome measures were depression, sleep quality, mental flexibility and cognition, and physical fatigue. Results Niacin treatment was tolerated well by 45 subjects. The baseline mean UPDRS III score was 21.3 ± 15.8 for the niacin group and 22.4 ± 11.8 for placebo. The change with six months of placebo was 1.5 [95% CI, -0.73 to 3.73], and niacin was − 1.06 [95% CI, -3.68 to 1.57]. From six to twelve months, the average UPDRS III score decreased for the placebo group by 2.66 [95% CI, -0.95 to 6.24] and the niacin group by 4.63 [95% CI, 1.42 to 7.83]. Eight subjects withdrew from the study before the 6-month time point and eight more before the one-year time point due to voluntary discontinuation, flushing, or inability to continue (SARS-CoV-2 shut-down). Conclusion Low-dose niacin supplementation may be helpful as an adjunct therapy in improving motor function in PD. Trial registration: Clinicaltrials.gov, NCT03462680. Registered 12 March 2018- Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03462680?term=gpr109A&draw=2&rank=1

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