TOPLINE: 

Lipoic acid (LA), an oral antioxidant supplement, was not associated with greater improvements in timed walking speed or other clinical outcomes in patients with progressive multiple sclerosis (MS) compared to placebo in a new phase 2b trial. Although LA was linked to reduced whole-brain atrophy and stabilized deep gray matter volume, it was also associated with a potential risk for proteinuria.

METHODOLOGY: 

• A phase 2b, double-blind, placebo-controlled randomized trial, conducted from 2018 to 2023, included more than 100 adults with primary or secondary progressive MS (mean age, 59 years; 55% women; 91% White; disease duration, 16.3 years).
• Participants had moderate disability (Expanded Disability Status Scale scores of 3.0-6.5) and evidence of relapse-independent disability progression within the previous 2 years.
• Participants were randomly assigned to receive either 1200 mg/d of oral LA (n = 54) or a placebo containing hypoallergenic plant fiber (n = 61) for 24 months. Follow-up visits were conducted every 6 months.
• The primary outcome was 24-month change in walking speed, as measured with the Timed 25-Foot Walk test. Secondary outcomes included brain atrophy, other clinical and patient-reported disabilities, and adverse events.

TAKEAWAY: 

• LA was not associated with a greater change in walking speed compared with placebo (mean change in speed, -0.39 vs -0.30 ft/sec, respectively; P = .5). There were also no significant between-group differences in mobility, disability, cognition, or patient-reported outcomes, including sleep, fatigue, and activity levels.
• Whole-brain volume loss was less in the LA group compared to the placebo group (-0.58 vs -7.18 cm³; P =.08), whereas deep gray matter volume remained stable in the LA group and atrophied in the placebo group (0.09 vs -0.31 cm³; P = .025).
• Total T2-weighted lesion volume increased significantly more in the LA group than in the placebo group (1.96 vs 0.30 cm³; P = .01).
• The LA group had more discontinuations compared to the placebo group (37% vs 17%), as well as higher rates of proteinuria (20.4% vs 3.3%) and a greater decline in estimated glomerular filtration rate (24% vs 14.8%). One suspected case of neural epidermal growth factor-like 1-associated membranous nephropathy occurred in the LA group. There were no reports of suicidal ideation in the LA group compared with 14 reports in the placebo group.

IN PRACTICE:

Overall, LA “didn’t work clinically in progressive multiple sclerosis the way we hoped,” lead investigator Rebecca Spain, MD, Veterans Affairs Portland Health Care System, Portland, Oregon, said in a press release. 

“However, the slowing of brain atrophy that we saw in MRI images suggests that we may yet be on the right track, especially if we can find a better way to deliver the beneficial effects of an antioxidant like lipoic acid,” Spain added.

SOURCE:

The study was published online on December 15 in Neurology.

LIMITATIONS:

The study was potentially underpowered to detect clinically meaningful effects because of a modest sample size and missing data because of COVID-related interruptions. Enrollment of older, more disabled participants limited generalizability. In addition, a high rate of dropout and study discontinuation could have biased outcomes.

DISCLOSURES:

The study was funded by the Department of Veterans Affairs, National Multiple Sclerosis Society, MS Canada, and National Center for Advancing Translational Sciences. Several investigators reported having consulting or other roles with and/or receiving grant support from various pharmaceutical companies and research organizations. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.