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Thyroid Hormone for Remyelination in Multiple Sclerosis (MS): A Safety and Dose Finding Study (MST3K)

Primary Purpose

Multiple Sclerosis

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

Liothyronine sodium

Placebo

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring Thyroid hormone, Remyelination

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Oregon Health and Science University

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Liothyronine (cytomel)

Placebo

Arm Description

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

Subject will take matching placebo twice a day for one week

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT02760056

First Posted

April 5, 2016

Last Updated

May 24, 2018

Sponsor

Oregon Health and Science University

1. Study Identification

Unique Protocol Identification Number

NCT02760056

Brief Title

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

Acronym

MST3K

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

June 6, 2016 (Actual)

Primary Completion Date

January 10, 2017 (Actual)

Study Completion Date

January 10, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Oregon Health and Science University

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Multiple Sclerosis

Keywords

Thyroid hormone, Remyelination

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Sequential Assignment

Model Description

Dose escalation with monitoring for safety and tolerability, as well as reliability of VEP testing.

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Double-blind, randomized, controlled

Allocation

Randomized

Enrollment

15 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Liothyronine (cytomel)

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Subject will take matching placebo twice a day for one week

Intervention Type

Drug

Intervention Name(s)

Liothyronine sodium

Other Intervention Name(s)

Cytomel

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Patient will receive a matching placebo to take twice daily for one week.

Primary Outcome Measure Information:

Title

Determine the Maximum Tolerated Dose (MTD) of Oral L-T3 in Subjects With MS

Description

MTD per protocol (dose level one category below dose at which study was stopped due to intolerance or meeting criteria for cessation)

Time Frame

1 week

Secondary Outcome Measure Information:

Title

Reliability of Visual Evoked Potential (VEP) Testing (ICC)

Description

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.

Time Frame

1 week

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michelle Cameron, MD

Organizational Affiliation

OHSU Department of Neurology

Official's Role

Principal Investigator

Facility Information:

Facility Name

Oregon Health and Science University

City

Portland

State/Province

Oregon

ZIP/Postal Code

97239

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

Citations:

PubMed Identifier

32120028

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.

Results Reference

derived

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

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