search
Back to results

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

Primary Purpose

Multiple Sclerosis, Cognition

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
lipoic acid and omega-3 fatty acids
Placebo
Sponsored by
Oregon Health and Science University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring multiple sclerosis, cognition, clinical trial, thiotic acid, Omega-3 fatty acids

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Oregon Health and Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

lipoic acid and omega-3 fatty acids

placebo

Arm Description

lipoic acid and omega-3 fatty acids

placebo oil and placebo lipoic acid

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
May 6, 2014
Last Updated
May 2, 2017
Sponsor
Oregon Health and Science University
Collaborators
National Multiple Sclerosis Society
search

1. Study Identification

Unique Protocol Identification Number
NCT02133664
Brief Title
Lipoic Acid and Omega-3 Fatty Acids for Cognitive Impairment in Multiple Sclerosis
Official Title
Lipoic Acid and Omega-3 Fatty Acids for Cognitive Impairment in Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oregon Health and Science University
Collaborators
National Multiple Sclerosis Society

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Cognition
Keywords
multiple sclerosis, cognition, clinical trial, thiotic acid, Omega-3 fatty acids

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Arm Title
lipoic acid and omega-3 fatty acids
Arm Type
Experimental
Arm Description
lipoic acid and omega-3 fatty acids
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
placebo oil and placebo lipoic acid
Intervention Type
Drug
Intervention Name(s)
lipoic acid and omega-3 fatty acids
Other Intervention Name(s)
thiotic acid, fish oil, fish oil concentrate
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
placebo lipoic acid and placebo oil
Intervention Description
placebo lipoic acid and placebo oil
Primary Outcome Measure Information:
Title
Paced Auditory Serial Addition Task (PASAT)
Description
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.
Time Frame
Baseline to 12 weeks
Title
Stroop Color-Word Test
Description
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.
Time Frame
baseline to 12 weeks
Title
California Verbal Learning Test-II (CVLT-II)
Description
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.
Time Frame
baseline to 12 weeks
Title
Controlled Oral Word Association Test (COWAT)
Description
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.
Time Frame
baseline to 12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lynne Shinto, ND, MPH
Organizational Affiliation
Oregon Health and Science University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oregon Health and Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

We'll reach out to this number within 24 hrs