Identification of Non-responders to Levothyroxine Therapy

Study Overview
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Brief Summary
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The purpose of this study is to assess differential effects of T4 and T3 on cell and tissue level

Detailed Description
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15-20% of the patients with hypothyroidism remain symptomatic, despite adequate thyroxine substitution. Endocrinologists are split in their opinion on combination therapy with T4 and T3 on patients with poorly regulated hypothyroidism. There are no objective means, by which to identify individuals who would benefit from combination therapy. The purpose of this study is to assess differential effects of T4 and T3 on body temperature, metabolism, muscle strength and brain function. The main aim is to try to identify biomarkers reflecting different effects of T4 and T3 on cell and tissue level.

Official Title
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A Randomized Crossover Study, Examining Differential Effects of Levothyroxine and Liothyronine

Conditions
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Hypothyroidism, Biomarkers, Endocrine System Diseases

Intervention / Treatment
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* Drug: Levothyroxin
* Drug: Liothyronine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Poorly regulated hypothyroidism Female aged between 18 and 65 years Written informed consent obtained from the patient according to national regulations Exclusion Criteria: Cardiovascular disease Chronic liver disease Chronic kidney disease Any other endocrinological disease Use of beta blockers Pregnant or lactating females Hormonal substitution other than T3 and T4 Known psychiatric disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: T4<br> | Drug: Levothyroxin<br>* 3 months<br>|
| Experimental: T3<br> | Drug: Liothyronine<br>* 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brown adipose tissue activation | Thermal imaging of supraclavicular fossa | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body temperature | Rectal thermometer | 6 months | 
| Energy expenditure | Indirect calorimetry | 6 months | 
| Muscle strength | Hand grip test | 6 months | 
| ThyPRO Questionnaire | Thyroid patient reported outcome, 13 multi-item scale, range 0-100 with higher scores indicating poorer health status | 6 months | 
| Mean levels of thyroid hormones | TSH, free T4 and free T3 | 6 months | 
| SF-36 Questionnaire | Short form health survey, 8 multi-item scale, range 0-100 with higher scores indicating better health status | 6 months | 
| Fatigue Questionnaire | 11 item, range 0-33 with higher scores implying higher levels of fatigue | 6 months | 
| New biomarkers | Bone marrow fat, serum and urine | 6 months | 
| Micro-RNA, miR-92a | Serum exosomes | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thyroxine, Triiodothyronine