Contributions
Abstract: 222
Type: Oral
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Objective: To determine if Lipoic acid (LA) is neuroprotective, reduces disability and improves quality of life, and is safe in a secondary progressive multiple sclerosis (SPMS) population.
Background: LA is an inexpensive and readily-available oral antioxidant. In the animal model of MS, LA decreases inflammation and reduces optic nerve and spinal cord atrophy. LA reaches therapeutic blood levels and is tolerated at high doses in people with MS. The LA/dihydrolipoic acid redox couple is a key co-factor for pyruvate dehydrogenase in mitochondria which may relate to its mechanism of action in MS.
Methods: A 96 week, double-blind, randomised controlled trial of 1200mg daily LA versus placebo. Primary outcome was reduction in MRI whole brain atrophy. Secondary outcomes included atrophy of brain substructures and spinal cord, retinal and macular atrophy, changes in neurological exam, walking, cognition, fatigue, and quality of life. Adverse events (AEs) and safety laboratory measures were monitored throughout. Intention-to-treat analysis utilised linear mixed-models to evaluate the effect of LA on per 48 week rates of change in outcomes.
Results: Of the 54 randomised participants, 51 (27 LA and 24 placebo) took at least one dose of study drug and were included in analysis. Study arms were overall matched with an average age of 58.5±5.9 (40-69) years, 61 % female, disease duration of 29.6±9.5 (9-51) years, and median EDSS of 6.0 (3.0-9.0). Five participants (9.8 % of total), all taking LA, terminated early. Total and serious AEs were similar between groups, however there was significantly higher gastrointestinal upset and lower numbers of falls in LA participants. Compliance, measured by pill counts, was >80 %. Annualised rate of whole brain atrophy was significantly lower at 96 weeks in the LA group compared to placebo (slope= -0.22 vs. -0.65, p=0.004). On treatment two year volume loss was -0.4 % (0.7) for LA and (-1.3 % (1.1) for placebo (p=0.006). Walking speed improved in the LA group (p=0.057).
Conclusions: This highly promising pilot trial of LA demonstrated a significant reduction in whole brain atrophy and suggested a clinical benefit in SPMS while maintaining safety, tolerability, and high compliance over 96 weeks. A larger trial is necessary to confirm the neuroprotective effects, explore clinical benefits, and ensure the safety of LA in progressive MS populations.
Disclosure:
Rebecca I Spain: nothing to disclose.
Katherine Powers: nothing to disclose.
Charles Murchison: nothing to disclose.
Elizabeth Heriza nothing to disclose.
Fay Horak: nothing to disclose.
Jack Simon: nothing to disclsose.
Dennis N. Bourdette: nothing to disclose.
Study supported by: Department of Veterans Affairs, RR&D Service, Pure Encapsulations, Sudbury, MA.
Abstract: 222
Type: Oral
Abstract Category: Therapy - disease modifying - Treatment of progressive MS
Objective: To determine if Lipoic acid (LA) is neuroprotective, reduces disability and improves quality of life, and is safe in a secondary progressive multiple sclerosis (SPMS) population.
Background: LA is an inexpensive and readily-available oral antioxidant. In the animal model of MS, LA decreases inflammation and reduces optic nerve and spinal cord atrophy. LA reaches therapeutic blood levels and is tolerated at high doses in people with MS. The LA/dihydrolipoic acid redox couple is a key co-factor for pyruvate dehydrogenase in mitochondria which may relate to its mechanism of action in MS.
Methods: A 96 week, double-blind, randomised controlled trial of 1200mg daily LA versus placebo. Primary outcome was reduction in MRI whole brain atrophy. Secondary outcomes included atrophy of brain substructures and spinal cord, retinal and macular atrophy, changes in neurological exam, walking, cognition, fatigue, and quality of life. Adverse events (AEs) and safety laboratory measures were monitored throughout. Intention-to-treat analysis utilised linear mixed-models to evaluate the effect of LA on per 48 week rates of change in outcomes.
Results: Of the 54 randomised participants, 51 (27 LA and 24 placebo) took at least one dose of study drug and were included in analysis. Study arms were overall matched with an average age of 58.5±5.9 (40-69) years, 61 % female, disease duration of 29.6±9.5 (9-51) years, and median EDSS of 6.0 (3.0-9.0). Five participants (9.8 % of total), all taking LA, terminated early. Total and serious AEs were similar between groups, however there was significantly higher gastrointestinal upset and lower numbers of falls in LA participants. Compliance, measured by pill counts, was >80 %. Annualised rate of whole brain atrophy was significantly lower at 96 weeks in the LA group compared to placebo (slope= -0.22 vs. -0.65, p=0.004). On treatment two year volume loss was -0.4 % (0.7) for LA and (-1.3 % (1.1) for placebo (p=0.006). Walking speed improved in the LA group (p=0.057).
Conclusions: This highly promising pilot trial of LA demonstrated a significant reduction in whole brain atrophy and suggested a clinical benefit in SPMS while maintaining safety, tolerability, and high compliance over 96 weeks. A larger trial is necessary to confirm the neuroprotective effects, explore clinical benefits, and ensure the safety of LA in progressive MS populations.
Disclosure:
Rebecca I Spain: nothing to disclose.
Katherine Powers: nothing to disclose.
Charles Murchison: nothing to disclose.
Elizabeth Heriza nothing to disclose.
Fay Horak: nothing to disclose.
Jack Simon: nothing to disclsose.
Dennis N. Bourdette: nothing to disclose.
Study supported by: Department of Veterans Affairs, RR&D Service, Pure Encapsulations, Sudbury, MA.