Clinical trial NCT02760056: Thyroid Hormone for Remyelination in Multiple Sclerosis (MS): A Safety and Dose Finding Study
Official title: Thyroid Hormone for Remyelination in Multiple Sclerosis (MS): A Safety and Dose Finding Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Keywords: Thyroid hormone
Remyelination
Lead sponsor: Oregon Health and Science University
Sponsor class: OTHER
First posted: 2016-05-03
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Dose escalation with monitoring for safety and tolerability, as well as reliability of VEP testing.
Primary purpose: TREATMENT

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

Detailed description: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Determine the Maximum Tolerated Dose (MTD) of Oral L-T3 in Subjects With MS
timeFrame: 1 week
Secondary outcomes:
measure: Reliability of Visual Evoked Potential (VEP) Testing (ICC)
timeFrame: 1 week
Other outcomes:
Locations:
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
Study officials:
affiliation: OHSU Department of Neurology
name: Michelle Cameron, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wooliscroft L, Altowaijri G, Hildebrand A, Samuels M, Oken B, Bourdette D, Cameron M. Phase I randomized trial of liothyronine for remyelination in multiple sclerosis: A dose-ranging study with assessment of reliability of visual outcomes. Mult Scler Relat Disord. 2020 Jun;41:102015. doi: 10.1016/j.msard.2020.102015. Epub 2020 Feb 20.