Gastrointestinal Tolerability and Absorption of R‐ Versus R,S‐ Lipoic Acid in Progressive Multiple Sclerosis: A Randomized Crossover Trial

2020 ◽  
Vol 60 (8) ◽  
pp. 1099-1106
Author(s):  
Michelle Cameron ◽  
Cassidy Taylor ◽  
Jodi Lapidus ◽  
Katrina Ramsey ◽  
Dennis Koop ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Lipoic Acid ◽  
Crossover Trial ◽  
Progressive Multiple Sclerosis ◽  
Randomized Crossover Trial ◽  
Gastrointestinal Tolerability

scholarly journals Systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis

2020 ◽  
pp. jnnp-2020-324286
Author(s):  
Nick Cunniffe ◽  
Khue Anh Vuong ◽  
Debbie Ainslie ◽  
David Baker ◽  
Judy Beveridge ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trial ◽  
Lipoic Acid ◽  
Systematic Approach ◽  
Progressive Multiple Sclerosis ◽  
Evidence Based ◽  
Short List ◽  
Expert Review ◽  
Clinical Literature ◽  
Independent Expert

ObjectiveTo establish a rigorous, expert-led, evidence-based approach to the evaluation of licensed drugs for repurposing and testing in clinical trials of people with progressive multiple sclerosis (MS).MethodsWe long-listed licensed drugs with evidence of human safety, blood–brain barrier penetrance and demonstrable efficacy in at least one animal model, or mechanistic target, agreed by a panel of experts and people with MS to be relevant to the pathogenesis of progression. We systematically reviewed the preclinical and clinical literature for each compound, condensed this into a database of summary documents and short-listed drugs by scoring each one of them. Drugs were evaluated for immediate use in a clinical trial, and our selection was scrutinised by a final independent expert review.ResultsFrom a short list of 55 treatments, we recommended four treatments for immediate testing in progressive MS: R-α-lipoic acid, metformin, the combination treatment of R-α-lipoic acid and metformin, and niacin. We also prioritised clemastine, lamotrigine, oxcarbazepine, nimodipine and flunarizine.ConclusionsWe report a standardised approach for the identification of candidate drugs for repurposing in the treatment of progressive MS.

A double-blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis

Neurology ◽  
1992 ◽  
Vol 42 (8) ◽  
pp. 1468-1468 ◽  
Author(s):  
B. G. Weinshenker ◽  
M. Penman ◽  
B. Bass ◽  
G. C. Ebers ◽  
G. P. A. Rice
Keyword(s):  
Multiple Sclerosis ◽  
Crossover Trial ◽  
Double Blind ◽  
Randomized Crossover Trial

Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine

2001 ◽  
Vol 7 (6) ◽  
pp. 354-358 ◽  
Author(s):  
P.M. Rossini ◽  
P. Pasqualetti ◽  
C. Pozzilli ◽  
M.G. Grasso ◽  
E. Millefiorini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Crossover Trial ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Double Blind Placebo

Fatigue in progressive multiple sclerosis: results of a randomized, double-blind, placebo-controlled, crossover trial of oral 4-aminopyridine

2001 ◽  
Vol 7 (6) ◽  
pp. 354-358 ◽  
Author(s):  
P M Rossini ◽  
P Pasqualetti ◽  
C Pozzilli ◽  
M G Grasso ◽  
E Millefiorini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Functions ◽  
Crossover Trial ◽  
Motor Evoked Potentials ◽  
Symptomatic Treatment ◽  
Progressive Multiple Sclerosis ◽  
Double Blind ◽  
Fatigue Severity ◽  
High Level ◽  
Synaptic Mechanisms

Previous studies suggest that aminopyridine may play a role in the symptomatic treatment of fatigue in multiple sclerosis. Although the mechanism underlying the beneficial effect on fatigue remains unclear, it has been proposed that aminopyridines may help to improve conduction in demyelinated central pathways, implicating both axonal and synaptic mechanisms. The objective of the present study is to determine whether 4-AP decreases daily-living fatigue in progressive multiple sclerosis. The effect of 4-AP on other neurophysiological and neuropsychological parameters was also considered. A `double-blind', randomized, `placebo-controlled', crossover trial was conducted on 54 patients with progressive multiple sclerosis. All patients received treatment with placebo and 32 mg per day of 4-AP, each for 6 months. The main outcome measure was the Fatigue Severity Scale. Secondary measures were EDSS, cognitive functions and neurophysiological parameters. Forty-nine patients (91%) completed the study. Changes in fatigue scores, EDSS and cognitive functions were not significantly different between 4-AP and placebo. However, when patients treated with 4-AP were divided into two groups according to the serum level of 4-AP, a significant effect on fatigue compared with placebo was observed in the `high level' (430 ng/ml) group (P=0.05). Synchronization of motor evoked potentials improved during 4-AP with respect to placebo (P=0.019) and this correlated positively with fatigue reduction (P=0.010). No relevant side effects were observed.

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