Open-label Study of Liothyronine in MS
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|ClinicalTrials.gov Identifier: NCT02506751|
Recruitment Status : Completed
First Posted : July 23, 2015
Last Update Posted : February 12, 2018
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Secondary Progressive Multiple Sclerosis, Primary Progressive||Drug: liothyronine||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
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
- The incidence rate of adverse events [ Time Frame: 26 weeks ]
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
|United States, Maryland|
|The Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|Principal Investigator:||Scott Newsome, DO||Johns Hopkins University|