Thyroid Hormone for Remyelination in Multiple Sclerosis (MS): A Safety and Dose Finding Study

Study Overview
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Brief Summary
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This is a phase 1 study evaluating the safety and maximum tolerated dose of Liothyronine (T3) in subjects with multiple sclerosis

Detailed Description
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This is a pilot, phase I, placebo controlled clinical trial of short-term high-dose thyroid hormone to promote remyelination in MS. Permanent clinical disability in MS is likely caused by the neuronal damage and degeneration that follows recurrent demyelination with progressive failure of remyelination. Thyroid hormone (TH) is required for central nervous system (CNS) myelination during development, and CNS remyelination in animal models of MS, a process similar to developmental myelination, has also been found to be promoted by TH. This study will ascertain the safety, tolerability and maximum tolerated dose of TH in people with MS, explore reliability for a potential signal of treatment efficacy and mechanism, and optimize procedures for a full scale clinical trial to evaluate the efficacy of pulsed TH for promotion of remyelination in MS. The safety and tolerability of this treatment will be assessed using subjects' self-report of symptoms, the validated Hyperthyroid Symptom Scale (HSS), and blood pressure measurements. a

Official Title
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Thyroid Hormone for Remyelination in Multiple Sclerosis (MS): A Safety and Dose Finding Study

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Liothyronine sodium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of MS of any type Age 18 to 50 years Weight range 45-90 kg (100-200 lbs) Lesions on brain MRI Exclusion Criteria: History of hypo or hyperthyroidism and a normal TSH History of high blood pressure (hypertension) [ Resting blood pressure greater than 150/95, resting heart rate greater than 100 History of coronary artery disease or clinically significant arrhythmia, clinically significant abnormalities on EKG History of diabetes History of anemia or renal (kidney) disease Clinically significant abnormalities on metabolic panel or serum hematocrit below 32 % History of atrophic gastritis History of anxiety disorder or bipolar disorder Serious psychiatric or medical conditions that would preclude reliable participation in the study Use of illicit substances or alcohol abuse Current use of fingolimod (Gilenya) Current or prior use of mitoxantrone (Novantrone) Current use of stimulants (methylphenidate, atomoxetine, dextroamphetamine,phentermine) Current use of any blood thinners such as warfarin or apixaban (Aspirin is ok) Medications which would metabolized faster in the presence of thyroid hormone (Insulin, oral hypoglycemic agents and oral anticoagulants) Severe head tremors (which would impair the ability to perform VEPs) Present or recent use of medications that could interact with the thyroid hormone (iodine containing agents such as kelp supplements, amiodarone, iodinated contrast given for CT or xray), P450 stimulants (phenytoin, carbamazepine, phenobarbital, and rifampin) Corrected visual acuity worse than 20/50 in either eye or other eye issues that would prevent reading of a standard eye chart Head tremors or other tremors that would prevent sitting relatively still for a vision test Patients taking proton pump inhibitors (PPIs) or H2 blockers will be excluded unless they can safely not take these medications during the week of study drug administration. Patients taking Ampyra (dalfampridine) will be excluded unless they can safely not take these medications during the week of study drug administration. Pregnancy, breastfeeding, or intention to become pregnant in the following month Inability to receive an MRI (e.g. implanted metal device)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Sequential Assignment
Interventional Model Description: Dose escalation with monitoring for safety and tolerability, as well as reliability of VEP testing.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liothyronine (cytomel)<br>Subjects will be divided into 4 groups. The first group will take 25 mcg twice daily for one week. The second group will take 37.5 mcg twice daily for one week. The third group will take 50 mcg twice daily for one week. The firth group will take 75 mcg twice daily for one week | Drug: Liothyronine sodium<br>* Subjects will be divided into 4 groups of progressively escalating doses. Each group will have 6 subjects 4 will receive the active treatment and 2 will receive the placebo. The first group will receive 25 mcg twice daily for one week. The second group will receive 37.5 mcg twice daily for one week. The third group will receive 50 mcg twice daily for one week. The forth group will receive 75 mcg twice daily for one week.<br>* Other names: Cytomel;|
| Placebo Comparator: Placebo<br>Subject will take matching placebo twice a day for one week | Drug: Placebo<br>* Patient will receive a matching placebo to take twice daily for one week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Maximum Tolerated Dose (MTD) of Oral L-T3 in Subjects With MS | MTD per protocol (dose level one category below dose at which study was stopped due to intolerance or meeting criteria for cessation) | 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reliability of Visual Evoked Potential (VEP) Testing (ICC) | P100 latency will be compared before and after treatment with L-T3 in subjects receiving the active treatment to assess reliability of the test for future assessment of treatment effect. | 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroid hormone, Remyelination