The primary aim is to collect data to determine the correct effect size on the primary outcome to aid in the design of a larger study: The primary outcome is to determine if lipoic acid and omega-3 fatty acids can improve cognitive function in people with multiple sclerosis that have cognitive dysfunction.

The study is designed as a randomized, double-blind, placebo-controlled pilot trial. The primary aim of the study is to determine if lipoic acid and omega-3 fatty acids can improve cognitive function over 12-weeks in people with multiple sclerosis that have a baseline score of at least two standard deviations below normative values on any one of four cognitive tests that include, Paced Auditory Serial Addition Task (PASAT), Stroop Color-Word Test, California Verbal Learning Test-II (CVLT-II), and Controlled Oral Word Association Test (COWAT).

The secondary aim is to determine treatment effects on markers of endothelial inflammation, insulin dysregulation, and mitochondrial dysfunction that may be related to cognitive dysfunction by measuring soluble intercellular adhesion molecule-1 (sICAM-1) levels, homeostasis model of insulin resistance (HOMA-IR), and MRI phosphorus imaging in a subset of study participants. The study will also measure safety by adverse event reports and laboratory measures; plasma fatty acid levels; serum lipoic acid levels.

Inclusion Criteria:

• • A definite diagnosis of multiple sclerosis (MS) with relapsing remitting or secondary progressive course

  • Age 18 to 65 years, inclusive
  • A score two or more standard deviations below the mean in one or more of the following cognitive tests: PASAT, COWAT, CVLT -II, Stroop
  • Expanded Disability Status Scale (EDSS) 0-7.5, inclusive
  • Suboptimal omega-3 levels (plasma docosahexaenoic acid [DHA] + eicosapentaenoic acid [EPA] < 5.0% of total plasma fatty acids)
  • If taking MS disease modifying medications, on stable dose for > 6 months preceding enrollment
  • Able to read and write English

Exclusion Criteria:

• • Moderate to severe depression (Beck Depression Inventory score > 19)

  • Any significant uncontrolled medical problem including diabetes requiring insulin.
  • MS relapse within the 30 days before screening
  • Abnormalities of coagulation or current use of prescription anticoagulants or antiplatelet agents. Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are not excluded.
  • Fish intake of one 6 ounce serving > once a week less than 2 months prior to enrollment
  • Omega-3 fatty acid supplement intake (e.g. fish oil capsules, cod liver oil) less than 2 months prior to enrollment
  • Lipoic Acid supplementation less than 1 month prior to enrollment
  • Taking systemic corticosteroids, neuroleptics, antiparkinsonian agents, and/or narcotic analgesics. Low dose sinemet and dopamine agonist taken once a day for restless leg syndrome is not an exclusion.
  • Contraindications to MRI, including: subjects with intrathecal pumps, stimulators, pacemakers, aneurysm clips, non-removable hearing aids, or metal fragments in the eyes. Other exclusion criteria include the inability to lie flat on the back for 40 minutes at a time or a self-reported history of claustrophobia. Subjects with a history of hip replacement and those with well-documented, verifiable, MRI-safe cardiac stents will not be excluded from the study.
  • Epilepsy or history of seizures.
  • Pregnancy or women not using a reliable form of contraception
  • Corrected binocular visual acuity worse than 20/50 or more than one error on binocular color vision testing with the Ishihara Color plates or sustained nystagmus or diplopia on primary gaze
  • Inability to complete the neuropsychological test battery at the screening visit
  • Participation in another intervention study

12 weeks