ECTRIMS Online Library

Gastrointestinal tolerability and absorption of R-versus racemic lipoic acid in progressive multiple sclerosis: a randomized cross-over trial
ECTRIMS Online Library. Spain R. 09/11/19; 278748; P387
Rebecca Spain
Rebecca Spain
Contributions
Abstract

Abstract: P387

Type: Poster Sessions

Abstract Category: Clinical aspects of MS - Progressive MS

R. Spain1,2, C. Taylor1, J. Lapidus1,3, M. Cameron1,2

1Oregon Health & Science University, 2Portland Veterans Affairs Hospital, 3Oregon Health & Science University - Portland State University School of Public Health, Portland, OR, United States

Background: Studies in experimental autoimmune encephalomyelitis and a human pilot trial suggest that lipoic acid (LA), an inexpensive, over-the-counter antioxidant, may be an effective treatment for progressive multiple sclerosis (PMS). Unfortunately, the racemic LA (50:50 mix of R- and S- enantiomers) used in the pilot trial was poorly tolerated (gastrointestinal (GI) upset) and showed wide variations in absorption. R-LA, the naturally-occurring enantiomer of LA supplied by the diet, is a key enzyme active in oxidative respiration and regenerates glutathione. We hypothesized that R-LA would be better tolerated, as needed for adherence, and better and more consistently absorbed, as needed for efficacy, than racemic LA.
Objectives: To compare the GI tolerability and serum absorption of oral R-LA versus racemic LA in people with PMS.
Methods: Adults with primary or secondary PMS (n=20) were enrolled in a single center, double-blind, randomized, crossover trial. Participants took equal numbers of capsules containing either 600mg R-LA or 1200mg racemic LA daily for 7-10 days, completed a ≥ 7 day washout, then took the other form of LA for 7-10 days. Participants were randomized to sequence of LA formulation. The Monitoring of Side Effects Scale (MOSES) GI questions (score range 0-44) were used to assess tolerability. Serum LA levels measured before and 60, 90, 120, 180, and 240 minutes after LA ingestion were used to assess absorption, based on areas under the curve (AUC) and maximum concentrations (Cmax).
Results: 20 participants enrolled (12 female, 8 male; 5 PPMS, 16 SPMS; mean 26.0 years from MS symptom onset; mean age 59.6 years). 17 took all study drug and completed all assessments. Three participants withdrew early due to symptoms - 2 when on racemic LA (fatigue and GI) and 1 when on R-LA (fatigue). There was a trend for R-LA being better tolerated than racemic LA, with a 1.9 lower MOSES score, adjusting for baseline MOSES score, order of treatments, and visit number (p=0.075). R-LA also demonstrated greater absorption with a 0.13 log mg.min/L higher AUC (p=0.025) and 0.21 log mg/ml higher Cmax (p=0.006). Absorption was also slightly more consistent, with a higher intra-subject correlation coefficient for AUC for R-LA (r=0.53) than for racemic LA (r=0.42).
Conclusions: R-LA appeared to be better tolerated and had greater and more consistent absorption than racemic LA in people with progressive MS. Clinical efficacy of R-LA needs to be determined.
Disclosure: Study Support: This study was supported by a grant from Race to Erase MS (121749), OHSU University Shared Resources (85135010), and a generous gift from Anne and Will Foster. Pure Encapsulations, LLC, provided the lipoic acid.
Rebecca Spain: nothing to disclose
Cassidy Taylor: nothing to disclose
Jodi Lapidus: nothing to disclose
Michelle Cameron: nothing to disclose

Abstract: P387

Type: Poster Sessions

Abstract Category: Clinical aspects of MS - Progressive MS

R. Spain1,2, C. Taylor1, J. Lapidus1,3, M. Cameron1,2

1Oregon Health & Science University, 2Portland Veterans Affairs Hospital, 3Oregon Health & Science University - Portland State University School of Public Health, Portland, OR, United States

Background: Studies in experimental autoimmune encephalomyelitis and a human pilot trial suggest that lipoic acid (LA), an inexpensive, over-the-counter antioxidant, may be an effective treatment for progressive multiple sclerosis (PMS). Unfortunately, the racemic LA (50:50 mix of R- and S- enantiomers) used in the pilot trial was poorly tolerated (gastrointestinal (GI) upset) and showed wide variations in absorption. R-LA, the naturally-occurring enantiomer of LA supplied by the diet, is a key enzyme active in oxidative respiration and regenerates glutathione. We hypothesized that R-LA would be better tolerated, as needed for adherence, and better and more consistently absorbed, as needed for efficacy, than racemic LA.
Objectives: To compare the GI tolerability and serum absorption of oral R-LA versus racemic LA in people with PMS.
Methods: Adults with primary or secondary PMS (n=20) were enrolled in a single center, double-blind, randomized, crossover trial. Participants took equal numbers of capsules containing either 600mg R-LA or 1200mg racemic LA daily for 7-10 days, completed a ≥ 7 day washout, then took the other form of LA for 7-10 days. Participants were randomized to sequence of LA formulation. The Monitoring of Side Effects Scale (MOSES) GI questions (score range 0-44) were used to assess tolerability. Serum LA levels measured before and 60, 90, 120, 180, and 240 minutes after LA ingestion were used to assess absorption, based on areas under the curve (AUC) and maximum concentrations (Cmax).
Results: 20 participants enrolled (12 female, 8 male; 5 PPMS, 16 SPMS; mean 26.0 years from MS symptom onset; mean age 59.6 years). 17 took all study drug and completed all assessments. Three participants withdrew early due to symptoms - 2 when on racemic LA (fatigue and GI) and 1 when on R-LA (fatigue). There was a trend for R-LA being better tolerated than racemic LA, with a 1.9 lower MOSES score, adjusting for baseline MOSES score, order of treatments, and visit number (p=0.075). R-LA also demonstrated greater absorption with a 0.13 log mg.min/L higher AUC (p=0.025) and 0.21 log mg/ml higher Cmax (p=0.006). Absorption was also slightly more consistent, with a higher intra-subject correlation coefficient for AUC for R-LA (r=0.53) than for racemic LA (r=0.42).
Conclusions: R-LA appeared to be better tolerated and had greater and more consistent absorption than racemic LA in people with progressive MS. Clinical efficacy of R-LA needs to be determined.
Disclosure: Study Support: This study was supported by a grant from Race to Erase MS (121749), OHSU University Shared Resources (85135010), and a generous gift from Anne and Will Foster. Pure Encapsulations, LLC, provided the lipoic acid.
Rebecca Spain: nothing to disclose
Cassidy Taylor: nothing to disclose
Jodi Lapidus: nothing to disclose
Michelle Cameron: nothing to disclose

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