RECRUITING

Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)

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Conditions

Multiple SclerosisTargeted TherapyBiomarkersCombination TherapyProgressive Multiple Sclerosis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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....

Official Title

Targeting Residual Activity By Precision, Biomarker-Guided Combination Therapies of Multiple Sclerosis (TRAP-MS)

Quick Facts

Study Start:2017-08-11
Study Completion:2029-01-01
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT03109288

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 120 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Enrolled in 09-I-0032 protocol.
  2. * Clinically definite MS.
  3. * Age greater than or equal to 18 years at time of study enrollment.
  4. * Expanded Disability Status Scale (EDSS) 1.0-7.5.
  5. * Documented sustained clinical progression of at least 0.5 CombiWISE points/year (measured by greater than or equal to 4 time-points regression analysis of CombiWISE values spanning at least 1.5 years in total).
  6. * Because currently only NDS utilizes CombiWISE scale, the progression slopes will be determined from NDS protocols: natural history protocol 09-I-0032 or any of the past NDS clinical trials (protocols 09-I-0197, 10-N-0212, 10-N-0125 and 13-I-0088). Consequently, new patients will be screened to this protocol via 09-I-0032 natural history protocol that contains completely overlapping procedures.
  7. * It is possible that after other MS centers start using CombiWISE scale, this progression criterion may be derived from outside data, as long as they are adequately documented.
  8. * Subjects of childbearing potential must be willing to use a medically acceptable form of birth control, while being treated on this study.
  9. * Patients who desire to continue their current FDA-approved DMTs based on its perceived (partial) therapeutic benefit will be enrolled with the understanding that the underlying FDA-approved therapy must remain stable during this protocol. If patient desires and/or his/her medical condition requires changing FDA-approved DMT during the duration of this protocol, the drugs administered under this protocol will be withdrawn, to establish new baseline of CSF biomarkers under changed therapy, and, if necessary, to establish new progression rate. New baseline of CSF biomarkers on changed therapy can be established after 6 months of new therapy. Because the efficacy of current DMTs decreases with patient s age so that on average, zero percent efficacy on disability progression occurs after age 53 (Weideman, Tapia-Maltos et al. 2017), only those patients who change to higher potency therapy (i.e., treatment escalation) before age 53 will need to repeat the entire process of establishing baseline progression rate: go back to greater than or equal to 1.5 year baseline period on new DMT to verify that the rate of progression remains greater than or equal to 0.5 CombiWISE points/year. Following therapeutic change that occurs before age 53 will be considered treatment escalation: 1. Initiation of any FDA-approved DMT in previously untreated subject or 2. Change from any low potency (i.e., copaxone, teriflunomide, interferon beta preparations, dimethyl or monomethyl fumarate and fingolimod) to any high potency drugs (i.e., natalizumab, ocrelizumab, rituximab, alemtuzumab, siponimod, cladribine, ofatumumab, ozanimod, ublituximab and mitoxantrone). All other therapy changes (i.e., parallel change from low efficacy to low efficacy or from high efficacy to high efficacy, as well as discontinuation of treatment after age 53) will require new CSF baseline (6 months after such therapy change), but will not require 18 months to calculate new CombiWISE slope. After new CSF baseline, and, if necessary, new CombiWISE progression slopes are established, patient can be matched to the same monotherapy or combination therapy regimen they were on before the immunomodulatory DMT change.
  10. * Willing and able to participate in all aspects of the protocol.
  11. * Able and willing to provide informed consent.
  1. * Clinically significant medical disorders that, in the judgment of the investigators, could expose the patient to undue risk of harm or prevent the patient from safely completing all required elements of the study (such as, but not limited to significant cerebrovascular disease, ischemic cardiomyopathy, clotting disorder, other neurodegenerative disorder, substance abuse or significant psychiatric disorder such as depression with suicidal ideations, unable to perform or tolerate MRI examinations).
  2. * Clinically significant medical disorders, other than MS, that require chronic treatment with immunosuppressive or immunomodulatory agents.
  3. * Pregnancy or breastfeeding.
  4. * Abnormal screening/baseline blood tests exceeding any of the limits defined below:
  5. * Serum alanine transaminase or aspartate transaminase levels which are greater than three times the upper limit of normal values.
  6. * Total white blood cell count less than 3,000/mm\^3.
  7. * Platelet count less than 85,000/mm\^3.
  8. * Serum creatinine level greater than 2.0 mg/dl and eGFR (glomerular filtration rate) less than 60.
  9. * Serological evidence of HIV, HTLV-1 or active hepatitis A, B or C.
  10. * Positive pregnancy test.
  11. * Pioglitazone
  12. * Congestive heart failure.
  13. * History of bladder carcinoma.
  14. * Type 1 diabetes.
  15. * Hypersensitivity to the drug.
  16. * Taking teriflunomide (Aubagio) because of risk of hypoglycemia on this combination.
  17. * Dantrolene
  18. * Hypersensitivity to the drug.
  19. * Hepatic impairment/active hepatic disease (cannot be paired with pirfenidone due to risk of cumulative hepatoxicity).
  20. * Persistent elevation of LFTs.
  21. * History of previous drug/medication or alcohol-related liver toxicities.
  22. * Pirfenidone
  23. * Hypersensitivity to the drug.
  24. * Hepatic impairment/active hepatic disease (cannot be paired with dantrolene due to risk of cumulative hepatoxicity).
  25. * Persistent elevation of LFTs.
  26. * Smoking.

Contacts and Locations

Study Contact

Michelle D Woodland
CONTACT
(301) 402-9619
michelle.woodland@nih.gov
Bibiana Bielekova, M.D.
CONTACT
(240) 669-2724
bielekovab@mail.nih.gov

Principal Investigator

Bibiana Bielekova, M.D.
PRINCIPAL_INVESTIGATOR
National Institute of Allergy and Infectious Diseases (NIAID)

Study Locations (Sites)

National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
United States

Collaborators and Investigators

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

  • Bibiana Bielekova, M.D., PRINCIPAL_INVESTIGATOR, National Institute of Allergy and Infectious Diseases (NIAID)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2017-08-11
Study Completion Date2029-01-01

Study Record Updates

Study Start Date2017-08-11
Study Completion Date2029-01-01

Terms related to this study

Keywords Provided by Researchers

  • Targeted Therapy
  • Multiple Sclerosis
  • Biomarkers
  • Combination Therapy
  • Progressive Multiple Sclerosis

Additional Relevant MeSH Terms

  • Multiple Sclerosis