Open-label Study of Liothyronine in MS

February 8, 2018 updated by: Johns Hopkins University

A Phase 1b, Open-label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals With MS

This study will evaluate the safety and tolerability of synthetic T3, liothyronine. It will establish if there are changes in MS symptoms and if there is a positive effect on markers of neuronal health.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Multiple sclerosis (MS) is a chronic, immune-mediated disease of the central nervous system (CNS) that is characterized by inflammation, demyelination, and neurodegeneration. It remains the most common non-traumatic cause of neurologic disability in young adults and presents in most patients as relapsing-remitting disease. Relapses, caused by inflammatory demyelination, can result in a significant amount of neurological disability and reduced health-related quality of life, and having frequent early relapses is associated with increased risk of longer-term disability. Clinical recovery from early relapses is incomplete in approximately half of patients with MS. The mechanisms underlying relapse recovery are not completely understood.

Remyelination of acutely denuded axons is one mechanism by which relapse recovery may occur. Remyelination is suspected to occur via newly differentiated oligodendrocytes, which are derived from oligodendrocyte precursor cells (OPCs) in the CNS. However, despite the presence of this innate repair mechanism, many patients go on to develop progressive functional disability. This may be due to a failure of remyelination or because of progressive axonal injury. Chronic demyelinating lesions are surrounded by OPCs and premyelinating oligodendrocytes, which suggest that failed remyelination does occur and could be partially due to incomplete oligodendrocyte differentiation. Additionally, recent studies have highlighted the importance of mitochondrial dysfunction, perhaps related to oxidative stress or increased energy demands, in mediating MS disease progression. Mitochondrial dysfunction may drive axonal degeneration with resultant neurodegeneration and progressive neurological decline (progressive MS). While numerous immune modulating therapies exist, currently, there is an urgent need for novel therapies that have neuroreparative and neuroprotective properties.

Thyroid hormones may play a direct role in remyelination and repair in the adult CNS by promoting maturation of oligodendrocytes. Further, thyroid hormones have been shown to reduce oxidative stress and thus may have the capacity to prevent mitochondrial dysfunction as well. Since tri-iodothyronine (T3) is believed to mediate the most important thyroid hormone actions, liothyronine (synthetic form of T3) has the potential to induce reparative mechanisms and limit secondary neurodegeneration in MS. In mice, T3 administration has shown to help facilitate recovery from cuprizone-induced demyelination. In this study, the investigators propose to perform a phase 1 study in patients with MS to establish a tolerable dose of liothyronine, evaluate the safety of this medication, determine whether it impacts function, and evaluate if it is associated with changes in neurotrophic and/or inflammatory biomarkers in the cerebrospinal fluid (CSF).

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • The Johns Hopkins Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 58 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Must meet 2010 McDonald criteria for clinically definite MS
  • Must be euthyroid
  • Expanded Disability Status Scale (EDSS) 3.0-7.5
  • Patients may be on MS immunomodulating therapies or immunosuppressant therapies during the study

Exclusion Criteria:

  • Known thyroid disease (past or current)
  • Currently on thyroid replacement therapy
  • Steroid use within a month of screening
  • History of coronary artery disease, atrial fibrillation, or other clinically significant cardiac disease
  • History of adrenal insufficiency
  • Ongoing renal and/or liver disease
  • Ongoing severe depression and/or anxiety
  • Use of carbamazepine, phenytoin, phenobarbital, warfarin, antacids, cholestyramine, colestipol, sucralfate, and rifampin
  • Known contraindication to using beta-blocker medications
  • History of alcohol or substance abuse in the past 6 months
  • Pregnant or nursing
  • If the investigator feels that participation in this study is not in the best interest of the subject

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Liothyronine

Subjects will take oral liothyronine for a total of 24 weeks following the below titration schedule:

0-6 weeks: liothyronine 10mcg po daily (5mcg po BID)

6-12 weeks: liothyronine 20mcg po daily (10mcg po BID)

12-18 weeks: liothyronine 50mcg po daily (25mcg po BID)

18-24 weeks: liothyronine 1mcg/kg/day (0.5mcg/kg po BID), not to exceed 75mcg po daily
Drug: liothyronine
All eligible subjects will be treated with the study drug as per the standardized dose-escalation protocol. Subjects will be required to report to the study site every six weeks for the duration of the study in order to receive their study drug and to monitor drug safety and tolerability.
Other Names:
  • Cytomel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The incidence rate of adverse events
Time Frame: 26 weeks
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Johns Hopkins University

Investigators

  • Principal Investigator: Scott Newsome, DO, Johns Hopkins University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2015

Primary Completion (Actual)

September 18, 2017

Study Completion (Actual)

September 18, 2017

Study Registration Dates

First Submitted

July 12, 2015

First Submitted That Met QC Criteria

July 21, 2015

First Posted (Estimate)

July 23, 2015

Study Record Updates

Last Update Posted (Actual)

February 12, 2018

Last Update Submitted That Met QC Criteria

February 8, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00061965

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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