Open-label Study of Liothyronine in MS
Condition: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Secondary Progressive; Multiple Sclerosis, Primary Progressive
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis, Chronic Progressive; Sclerosis
Study type: Interventional
Phase: Phase 1

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.
    

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).
    

Intervention name(s): liothyronine
Intervention type(s): Drug
Intervention description(s): 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 intervention name(s): Cytomel
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment