Improving White Matter Integrity With Thyroid Hormone

Study Overview
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Brief Summary
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Animal studies have shown that thyroid hormone can improve white matter integrity after damage to myelin, which insulates and protects nerves. It is currently unknown whether this type of repair can occur in humans. The purpose of the proposed study is to examine the impact of thyroid hormone on white matter integrity in humans using two complementary, state-of-the-art neuroimaging techniques: high angular diffusion imaging and multicomponent relaxometry.

Detailed Description
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The ability to promote and support remyelination has wide-ranging implications for a number of neuropsychiatric conditions from multiple sclerosis to major depression. Pre-clinical evidence has demonstrated that thyroid hormone treatment, in the form of triiodothyronine (T3) or tetraiodothyronine (T4), can promote and support remyelination by increasing myelin basic protein mRNA and protein, oligodendrocyte proliferation and maturation, and fractional anisotropy (a diffusion imaging measure of white matter integrity). Pilot data from the investigator's studies suggest that baseline thyroid status is correlated with the integrity of white matter tracts associated with major depression. To date, the impact of thyroid hormone administration on white matter tracts has not been studied in vivo in adult humans. The purpose of the proposed pilot study is to examine changes in white matter tract integrity using high angular diffusion imaging and multi-component relaxometry in a population of subjects clinically indicated to receive thyroid hormone for hypothyroidism. The investigators will scan patients with hypothyroidism at the initiation of treatment and at three and six months after starting thyroid hormone treatment. The investigators will also administer scales assessing mood and cognition which have been shown to correlate with white matter integrity. The investigators hypothesize that thyroid hormone treatment will be associated with an increase in fractional anisotropy, a decrease in radial diffusivity, and an increase in the myelin water fraction (markers of improved myelination) that will correlate with improvements in cognition and mood ratings. If successful, this will be the first demonstration of improved white matter integrity with thyroid hormone replacement and pave the way for therapies designed to restore structural brain connectivity.

Official Title
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Improving White Matter Integrity With Thyroid Hormone

Conditions
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Hypothyroidism

Intervention / Treatment
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* Drug: Levothyroxine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 21-60 years of age A diagnosis of primary hypothyroidism from autoimmune thyroiditis (Hashimoto) Able to give informed consent. Exclusion Criteria: Major depressive disorder with or without active suicidal ideation Mild or major neurocognitive disorder; Presence of contraindications to magnetic resonance imaging (presence of ferrous-containing metals within the body (e.g., aneurysm clips, shrapnel/retained particles) Inability to tolerate small, enclosed spaces without anxiety (e.g., claustrophobia) Unwilling/unable to sign informed consent document Positive urine drug screen results; Pregnancy (positive pregnancy test), trying to become pregnant, or lactation

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with primary hypothyroidism<br>All participants will receive the same treatment (levothyroxine, a synthetic T4 hormone replacement) at a dose that will be titrated using serum thyrotropin (TSH) levels as a goal, according to the American Thyroid Association Task Force recommendations | Drug: Levothyroxine<br>* All participants will be treated for their hypothyroidism according to the standard of care as reflected in recent guidelines from the American Thyroid Association.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High Angular Diffusion Tensor Imaging | Change in baseline white matter track integrity at 3 months and 6 months | 6 months | 
| Multi-Component Relaxometry | Change in baseline white matter track integrity at 3 months and 6 months | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Health Questionaire | Self-report measure of depression severity, Items are summed (Not at all = 0; Several days = 1; More than half the days = 2; Nearly every day = 3), yielding a score from 0 to 27 | Collected at Baseline, 3 month follow-up, 6 month follow-up | 
| NIH Toolbox : Dimensional Change Card Sort Test | Behavioral measures of executive functioning | Collected at Baseline, 3 month follow-up, 6 month follow-up | 
| NIH Toolbox : Pattern Comparison Processing Speed Test | Behavioral measures of processing-speed measure | Collected at Baseline, 3 month follow-up, 6 month follow-up | 
| NIH Toolbox : Flanker Inhibitory Control and Attention Test | Behavioral measures of attention | Collected at Baseline, 3 month follow-up, 6 month follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuroimaging, thyroid, white matter