Defining the Anti-inflammatory Role of Lipoic Acid in Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT00997438
• Recruitment Status: Completed
• First Posted: October 19, 2009
• Results First Posted: January 26, 2017
• Last Update Posted: January 26, 2017
• Sponsor: Portland VA Medical Center
• Collaborator: Oregon Health and Science University
• Information provided by (Responsible Party): Daniel Carr, Portland VA Medical Center

Tracking Information

• First Submitted Date: October 16, 2009
• First Posted Date: October 19, 2009
• Results First Submitted Date: September 30, 2016
• Results First Posted Date: January 26, 2017
• Last Update Posted Date: January 26, 2017
• Study Start Date: August 2010
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 30, 2016)

• Lipoic Acid Levels [ Time Frame: 1 hour ]
  Plasma concentration of LA
• Lipoic Acid Levels [ Time Frame: 2 hours ]
  Plasma concentration of LA
• Lipoic Acid Levels [ Time Frame: 3 hours ]
  Plasma concentration of LA
• Lipoic Acid Levels [ Time Frame: 4 hours ]
  Plasma concentration of LA
• Lipoic Acid Levels [ Time Frame: 24 hour ]
  Plasma concentration of LA
• Lipoic Acid Levels [ Time Frame: 48 hour ]
  Plasma concentration of LA
• cAMP Levels [ Time Frame: 2 hours ]
• cAMP Levels [ Time Frame: 4 hours ]

• Original Primary Outcome Measures (submitted: October 16, 2009): cAMP and lipoic acid levels [ Time Frame: 24 hour and 48 hour ]

Current Secondary Outcome Measures (submitted: November 30, 2016)

• RANTES Levels [ Time Frame: 24 hour ]
• RANTES Levels [ Time Frame: 48 hour ]

• Original Secondary Outcome Measures (submitted: October 16, 2009): cytokine and chemokine levels [ Time Frame: 24 hour and 48 hour ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Defining the Anti-inflammatory Role of Lipoic Acid in Multiple Sclerosis
• Official Title: Defining the Anti-inflammatory Role of Lipoic Acid in Multiple Sclerosis
• Brief Summary: The purpose of this study is to learn about how the antioxidant, lipoic acid, works in the body and how it may help in the management of relapsing remitting and secondary progressive multiple sclerosis. This study will compare how subject's and healthy volunteers bodies absorb and break down the supplement. This information may help in developing new therapies.

Detailed Description

Subjects (healthy control, relapsing remitting MS and secondary progressive MS) will be recruited through patients of investigators at Portland VA Medical Center (PVAMC), Oregon Health & Science University (OHSU), and the community using flyers and word of mouth.

The following will occur during screening:

• Medical History Questionnaire to include questions about drug and alcohol use
• Self Administered Expanded Disability Status Scale (EDSS) Questionnaire (MS participants only)
• Vital Signs (heart rate, respiratory rate, blood pressure) will be measured and recorded
• Physical Exam (MS participants only unless necessary, based on the Medical History Questionnaire or vital signs, to ensure participant safety)
• Neurological Exam (MS participants only unless necessary, based on the Medical History Questionnaire or vital signs, to ensure participant safety)
• Weight
• Urine pregnancy test, if applicable
• Anemia testing by finger stick (approximately 1 drop)

The rest of the study involves

• Blood draws before lipoic acid is given, 1 hour, 2 hours, 3 hours, 4 hours, 24 and 48 hours after LA is given (3 ½ tablespoons)
• Subjects will receive breakfast before they take LA
• Subjects will take 4 - 300 mg capsules of lipoic acid (LA) for a total of 1200mg with about 1 cup of water

Blood will be processed to obtain plasma (from which lipoic acid concentrations will be measured) and PBMCs (from which cAMP and cytokines/chemokines will be measured).

• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Sclerosis

Intervention

Dietary Supplement: Lipoic Acid

300 mg Lipoic acid tablets from Vital Nutrients

Study Arms

• Experimental: MS - Secondary Progressive
  1200 mg of Lipoic acid supplement
  Intervention: Dietary Supplement: Lipoic Acid
• Experimental: MS - Relapsing Remitting
  1200mg of Lipoic acid supplement
  Intervention: Dietary Supplement: Lipoic Acid
• Experimental: Healthy Controls
  1200 mg of Lipoic acid supplement
  Intervention: Dietary Supplement: Lipoic Acid

• Publications *: Fiedler SE, Yadav V, Kerns AR, Tsang C, Markwardt S, Kim E, Spain R, Bourdette D, Salinthone S. Lipoic Acid Stimulates cAMP Production in Healthy Control and Secondary Progressive MS Subjects. Mol Neurobiol. 2018 Jul;55(7):6037-6049. doi: 10.1007/s12035-017-0813-y. Epub 2017 Nov 15.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 30, 2016): 69
• Original Estimated Enrollment (submitted: October 16, 2009): 60
• Actual Study Completion Date: December 2013
• Actual Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion/Exclusion criteria for MS subjects.

Inclusion criteria:

1. Adult at least 18 years of age able to provide informed consent
2. Currently diagnosed with relapsing remitting or secondary progressive MS

Exclusion criteria:

1. Self-reported current substance/alcohol abuse/dependence or sobriety for less than 90 days
2. History of traumatic brain injury as defined by a loss of consciousness of greater than 30 minutes
3. History of a medical condition associated with persisting cognitive problems or serious central nervous system dysfunction (e.g., brain tumor,dementia)
4. MS exacerbation within 30 days of study entry
5. Systemically administered corticosteroids within 30 days of study entry
6. Pregnant or breast-feeding
7. Anti-coagulant use such as Heparin, Coumadin, or Aspirin while enrolled in the study
8. Other significant health problem (e.g. active coronary heart disease, liver disease, pulmonary disease, diabetes mellitus) that might increase the risk of subject experiencing adverse events
9. Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study
10. Anemia as indicated by a POC hemoglobin <12
11. Subjects of child bearing potential or subjects capable of causing pregnancy who are sexually active and unwilling to use effective contraceptive methods for the duration of the study

Inclusion/ Exclusion criteria for healthy controls.

Inclusion criteria:

1) Adult at least 18 years of age able to provide informed consent

Exclusion criteria:

1. Self-reported current substance/alcohol abuse/dependence or sobriety for less than 90 days
2. History of traumatic brain injury as defined by a loss of consciousness of greater than 30 minutes
3. History of a medical condition associated with persisting cognitive problems or serious central nervous system dysfunction (e.g., brain tumor,dementia)
4. Pregnant or breast-feeding
5. Anti-coagulant use such as Heparin, Coumadin, or Aspirin while enrolled in the study
6. Other significant health problem (e.g. active coronary heart disease, liver disease, pulmonary disease, diabetes mellitus) that might increase the risk of subject experiencing adverse events
7. Any condition which would make the subject, in the opinion of the investigator, unsuitable for the study
8. Anemia as indicated by a POC hemoglobin <12
9. Subjects of child bearing potential or subjects capable of causing pregnancy who are sexually active and unwilling to use effective contraceptive methods for the duration of the study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00997438
• Other Study ID Numbers: 5659; OHSU eIRB#5659 ( Other Identifier: OHSU )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Daniel Carr, Portland VA Medical Center
• Original Responsible Party: Daniel Carr, Oregon Health and Science University
• Current Study Sponsor: Portland VA Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Oregon Health and Science University

Investigators

• Principal Investigator: Daniel Carr, Ph.D; Portland VA Medical Center and Oregon Health & Science University

• PRS Account: Portland VA Medical Center
• Verification Date: November 2016