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

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

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)