Lipoic Acid and Omega-3 Fatty Acids for Cognitive Impairment in Multiple Sclerosis

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Lipoic Acid and Omega-3 Fatty Acids for Cognitive Impairment in Multiple Sclerosis

Conditions
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Multiple Sclerosis, Cognition

Intervention / Treatment
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* Drug: lipoic acid and omega-3 fatty acids
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: lipoic acid and omega-3 fatty acids<br>lipoic acid and omega-3 fatty acids | Drug: lipoic acid and omega-3 fatty acids<br>* alpha lipoic acid as racemic form at 1,200 mg per day omega-3 fatty acids as fish oil concentrate containing a daily dose of 1.35 grams docosahexanoic acid and 1.95 grams of eicosapentaenoic acid<br>* Other names: fish oil concentrate;|
| Placebo Comparator: placebo<br>placebo oil and placebo lipoic acid | Drug: Placebo<br>* placebo lipoic acid and placebo oil<br>* Other names: placebo lipoic acid and placebo oil;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paced Auditory Serial Addition Task (PASAT) | The PASAT is a measure of working memory and sustained attention frequently used in multiple sclerosis treatment outcome studies. The examinee is presented with a series of numbers at 2 second intervals on an audiotape and responds by always adding the last two numbers on the tape before the next number is presented. The change in total number of correct responses from baseline to 12 weeks is the measurement for the outcome. | Baseline to 12 weeks | 
| Stroop Color-Word Test | The Stroop test assess attention and executive function.The task consists of 3 tasks with only red, green, and blue colors used. The first task asks the subject to name the colors of spots on cards. If a subject can perform this task the second task is performed in which a subject must read the names of colors listed on cards (which are printed in congruent colors). In the third task, the subject is shown a series of words naming colors but the words and colors are mismatched; so the word yellow may be red, the word blue may be green and so forth. The subject is instructed to ignore the word and name the color. The subject will have the tendency to read the word rather than name the color, the so-called Stroop effect. This third part of the test is referred to as the interference condition and is the critical measurement. The change in time it takes to complete the interference from baseline to 12 weeks is the outcome measure. | baseline to 12 weeks | 
| California Verbal Learning Test-II (CVLT-II) | CVLT-II is a measure of verbal learning/memory. It is comprised of lists containing 16 words, each of which fit into one of four categories of shopping list items. Five trials are administered followed by presentation of a different list. Free and cued recall of the original list is assessed. The change in long delay free recall from baseline to 12 weeks will be the measurement used for outcome. | baseline to 12 weeks | 
| Controlled Oral Word Association Test (COWAT) | The COWAT is a letter fluency test. Participants are asked to generate as many words as possible beginning with a particular letter of the alphabet during one minute. Alternate versions using 3 letters are used for each examination. The change in total number of words produced for the 3 letters from baseline to 12 weeks will be the outcome. | baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis, cognition, clinical trial, thiotic acid, Omega-3 fatty acids