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

NCT02760056 | Completed Phase 1 Results DMC

• 1 other identifier: IRB 15101
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Multiple Sclerosis

Keywords

Thyroid hormone; Remyelination

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

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

  1 week

Study Arms (2)

Liothyronine (cytomel)

ACTIVE COMPARATOR

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

Placebo

PLACEBO COMPARATOR

Subject will take matching placebo twice a day for one week

Drug: Placebo

Interventions

Liothyronine sodium DRUG

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.

Also known as: Cytomel

Liothyronine (cytomel)

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Confirmed diagnosis of MS of any type
• Age 18 to 50 years
• Weight range 45-90 kg (100-200 lbs)
• Lesions on brain MRI

You may not qualify if:

• 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)

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Related Publications (1)

• 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.

  PMID: 32120028 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Triiodothyronine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thyronines; Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Thyroxine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Self-reporting of BP, HR. 1 missed dose in the drug arm. VEP testing was conducted by multiple technicians and read by multiple attending physicians; though visit one and two were more often conducted by the same tech/attending.

Results Point of Contact

• Title: Anna Orban
• Organization: OHSU

orban@ohsu.edu

503-494-3549

Study Officials

• Michelle Cameron, MD

  OHSU Department of Neurology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, randomized, controlled
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair and Roy & Eulalia Swank Family Research Professor

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

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: May 3, 2016
• Study Start: June 6, 2016
• Primary Completion: January 10, 2017
• Study Completion: January 10, 2017
• Last Updated: November 19, 2018
• Results First Posted: November 19, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share

Locations

US (1)