Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

Study Overview
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Brief Summary
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The investigators propose the following hypothesis: discontinuation of levothyroxine (LT4) for veterans with subclinical hypothyroidism (SCH) will be feasible, acceptable, and safe and will not negatively affect their Quality of Life (QoL). The investigators aim to evaluate the feasibility of LT4 discontinuation among veterans with SCH and determine the changes in QoL measures, lipids, and adverse events.

Detailed Description
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This is a pilot, randomized, double-blind, placebo-controlled trial. Methodology: The investigators will conduct a double-blind, placebo-controlled clinical trial where eligible veterans diagnosed with SCH and on LT4 will be 1:1 randomized to either continue LT4 or change to placebo. The primary outcome is intervention feasibility (willingness to enter the trial, recruitment rate, and completion rate). Secondary outcomes are: 1) changes in QoL measures (Hypothyroid Symptom [HSS] and Tiredness scale scores of the Thyroid-Specific Patient-Related Outcome Measure [ThyPRO], EuroQoL 5-Dimension Self-Report Questionnaire) measured at baseline, 6-8 weeks and 6 months and 2) changes in lipids assessed at baseline and 6 months, and 3) incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, fractures, acute myocardial infarction, stroke, acute coronary syndrome, heart failure, mortality).

Official Title
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Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism: a Pilot Randomized, Double-blinded, Placebo-controlled Study

Conditions
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Subclinical Hypothyroidism

Intervention / Treatment
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* Drug: Levothyroxine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Veterans diagnosis of SCH Exclusion Criteria: thyroid-stimulating hormone (TSH) > 10 milli-international units per liter (mlU/L) (at any point) Levothyroxine (LT4) dose more than 75 mcg daily use of antithyroid medications, amiodarone, tyrosine kinase inhibitors or lithium history of thyroidectomy or radioactive iodine therapy LT4 suppressive therapy for thyroid cancer, goiter, or inflammation pregnancy or plans for pregnancy in the next 6 months an unstable medical condition that would jeopardize safety or interfere with study participation severe hypothyroidism-related symptoms strong family history of hypothyroidism severe dyslipidemia hospitalization for major illness within the previous 4 weeks acute coronary artery syndrome, acute myocarditis, or pancarditis with the previous 12 months grade IV New York Heart Association heart failure receiving services from hospice lack of decision-making capacity terminal medical condition for which life expectancy would be less than 6 months not willing to stop LT4 self-reported non-adherence to LT4 therapy abnormal TSH at time of screening for participation (assessed during Baseline Visit)

Ages Eligible for Study
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Minimum Age: 18 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Levothyroxine group (sham discontinuation)<br>Continue the current dose of levothyroxine. The brand of levothyroxine to be used in this study will be Synthroid tablets of 25 mcg, 50 mcg, and 75 mcg (AbbVie Inc). | Drug: Levothyroxine<br>* Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.<br>* Other names: Synthroid;|
| Placebo Comparator: Placebo group (real discontinuation)<br>Stop the current dose of levothyroxine and take study placebo | Other: Placebo<br>* Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participants' Willingness to Enter the Trial | Percent of eligible participants approached who consented to participate during the recruitment phase. | The time from first consent signed to last consent signed. March 2021 to April 2022. | 
| Recruitment Rate | The number of enrolled (consented) participants divided by the length of the recruitment period. | The time from first consent signed to last consent signed. March 2021 to April 2022. 13 months. | 
| Completion Rate | Percentage of randomized participants who completed the trial. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score | The Hypothyroid Symptoms score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more symptoms. | Baseline, 6 weeks and 6 months | 
| Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score | The Tiredness score from the Thyroid-Related Quality of Life Patient-Reported Outcome (ThyPRO) questionnaire is assessed on a scale from 0 to 100, with higher scores indicating more tiredness. | Baseline, 6 weeks and 6 months | 
| Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6 | The EuroQoL [EQ] Group 5-Dimension Self-Report Questionnaire (EQ-5D) scores include the EQ-5D descriptive index, on a scale from -0.59 to 1.00. Higher scores indicate better quality of life. The EQ-5D scores include the score on the EQ visual-analogue scale (EQ-5D VAS), on a scale from 0 to 100. Higher scores indicate better quality of life. | 6 weeks and 6 months | 
| Lipid Levels | Differences in mean 6-month lipid levels after adjusting for gender and baseline lipid level. | 6 months |