Recruitment for the OCTOPUS trial, which explores alpha-lipoic acid and metformin in progressive multiple sclerosis (MS), is progressing well with nearly half of participants in stage 1 already randomized.
A poster presented at the
As of March 25, 2024, 189 of the 237 screened participants have been randomized, equating to nearly half (49%) of the planned stage 1 recruitment requirement. Of these, 119 (63%) gave a diagnosis of secondary progressive MS, and an overall mean time since MS onset of 20.6 years (SD, 10.5 y; range, 2.4-45.2 y), 14.8 y since MS diagnosis (SD, 9.2; range, 0.9-44.1 y), and 10.6 y since onset of MS progression (SD, 6.6; range, 2.2-30.1 y).
The poster was on behalf of the OCTOPUS investigators, which includes Jeremy Chataway, PhD, FRCP, a professor of neurology at University College London. OCTOPUS, the first multi-site, multi-arm multi-stage (MAMS) trial in progressive MS geared to compare several treatment arms, was launched in 2023. The study randomizes 125 patients each to either R/S alpha-lipoic acid, metformin, or placebo, and will used a 2-stage process to determine continuation of arms. Stage 2, which tests confirmed disability progression using a composite scoring of Extended Disability Status Scale (EDSS), 9-hole peg, and timed 25-foot walk, will require 600 participants per arm.
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Thus far, 18.5% of the the randomized participants had a baseline EDSS less than 5.5, while 81.5% had EDSS scores greater than 6.0. The study predominantly features White participants (94.2%), followed by lesser representation from Asian (3.7%), and Black (1.1%) patients. To date, 5271 participants have completed the initial online survey, and 2958 were then eligible for telephone screening.
OCTOPUS aims to help solve a major unmet need: available treatment options for progressive forms of MS. To date, ocrelizumab remains the only FDA-approved therapy for progressive MS. It is hypothesized that lipoic acid, an oral medication, may have an impact on the immune system, reducing the number of harmful immune cells that attack and damage myelin.2 Metformin, a drug used to treat type 2 diabetes, may be able to help repair myelin, and has shown an ability to push myelin-making cells to become fully developed, thus enabling better myelin repair.3
A 2019 preclinical study showed that use of metformin promoted myelin repair in rates, suggesting synergistic effects of rejuvenation and pro-differentiation therapies. In the study, investigators observed that the differentiation potential of adult rodent oligodendrocyte progenitor cells (OPCs) decreased with age. Fasting or treatment with metformin was shown to reverse changes in functional capacity and restore the regenerative capacity of aged OPCs, improving remyelination in aged animals following focal demyelination.4
Lipoic acid is also being studied in a phase 2 trial of progressive MS, dubbed LAMPS (NCT03161028). The 2-year trial, expected to include 115 participants, will test mobility using the 25-foot walk test and 2-minute timed walk test as well as fall counts. LAMPS, which is expected to have data read out in 2024, also includes assessment of neuroprotection, measured by the extent of brain volume loss seen on MRI.5
