Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)
National Institute of Allergy and Infectious Diseases (NIAID)
Summary
Background: In people with multiple sclerosis (MS), brain and cerebrospinal fluid (CSF) biomarkers indicate inflammation or disease. Researchers want to see if 4 drugs given alone or combined affect MS biomarkers. They want to see if a change in biomarker levels can predict which drugs a person with MS might respond to. Objective: To see if signs of inflammation in CSF help predict a person s response to different drugs. Eligibility: People ages 18 and older who: * Are in protocol 09-I-0032 * Have progressive MS * Can stand and walk a few steps * Take an MS drug Design: Participants will be screened in protocol 09-I-0032. Participants will take 1 of the 4 study drugs. Researchers will call after 1 month to see how they are doing. Some will start a second drug. They may take each drug or combination for up to 18 months. Participants will have 2 visits a year for up to 6 years. Visits include: * Medical history * Physical exam * Blood and heart tests * X-rays and scans * Eye exam and tear collection * Lumbar puncture: A needle inserted between back bones removes some CSF. * Lymphocytapheresis: Blood is removed through a needle in one arm and run through a machine. The blood is returned through a needle in the other arm. * A sensor on the forehead records blood flow and oxygen use. * Participants may get a device for testing at home. Participants will stop taking the drugs if they have taken 2 drugs together for 18 months or if they do not do well on the drugs. Participants will be called 3 months later to see how they are doing....
Description
Objective: Multiple pathogenic mechanisms drive progression of disability in fully established multiple sclerosis (MS); therefore, it is unlikely that a single therapeutic agent will be curative. Analogous to cardiovascular diseases, effective treatments for evolved MS will likely require individualized combination therapies that target pathogenic processes active in the particular patient. Ability to reliably measure such pathogenic mechanisms in living subjects is a prerequisite for a precisionmedicine approach to MS. We have already demonstrated the clinical utility of combinatorial cereb…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
* INCLUSION CRITERIA: * Enrolled in 09-I-0032 protocol. * Clinically definite MS. * Age \>=18 years at time of study enrollment. * Expanded Disability Status Scale (EDSS) 1.0-7.5. * For progressive MS cohort enrollment: * Documented sustained clinical progression of at least 0.5 CombiWISE points/year on stable therapy (or untreated) * If follow-up is \<3 years, CombiWISE progression slopes are measured by \>= 4 time points regression analysis of CombiWISE values spanning at least 18 months (1.5 years) * If follow-up is \>=3 years, CombiWISE progression slopes are measured by \>= 2…
Interventions
- DrugCilostazol
100 mg Bid
- DrugLeucovorin
10 mg Bid
- DrugPirfenidone
Up to 801 mg po tid. Slow titration over weeks based on tolerability: 267mg po tid x \>= 7d 534 mg po tid x \>= 7d 801 mg po tid
- DrugDantrolene
Up to 200 mg/day (divided into 3 doses of 50mg, 50mg, and 100 mg)
- DrugPioglitazone
15-45 mg po qd
Location
- National Institutes of Health Clinical CenterBethesda, Maryland