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Open-label Study of Liothyronine in MS

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02506751
Recruitment Status : Completed
First Posted : July 23, 2015
Last Update Posted : February 12, 2018
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Primary Progressive Drug: liothyronine Phase 1

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b, Open-label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals With MS
Study Start Date : July 2015
Actual Primary Completion Date : September 18, 2017
Actual Study Completion Date : September 18, 2017

Resource links provided by the National Library of Medicine


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 Name: Cytomel




Primary Outcome Measures :
  1. The incidence rate of adverse events [ Time Frame: 26 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 58 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02506751


Locations
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United States, Maryland
The Johns Hopkins Hospital
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Investigators
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Principal Investigator: Scott Newsome, DO Johns Hopkins University

Publications:

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT02506751    
Other Study ID Numbers: IRB00061965
First Posted: July 23, 2015    Key Record Dates
Last Update Posted: February 12, 2018
Last Verified: February 2018
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Multiple Sclerosis, Chronic Progressive
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases