Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

Phase 4

Completed

• Conditions: Subclinical Hypothyroidism
• Interventions: Other: Placebo; Drug: Levothyroxine

• Registration Number: NCT04288115
• Lead Sponsor: VA Office of Research and Development

Brief Summary

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

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).

Study Timeline

• Study First Submitted: 2020-02-14
• Study First Submitted QC: 2020-02-25
• Study First Posted: 2020-02-28
• Study Start: 2021-03-24
• Primary Completion: 2022-10-07
• Study Completion: 2022-12-31
• Results First Submitted: 2023-09-27
• Status Verified: 2023-11
• Results First Submitted QC: 2023-11-14
• Last Update Submitted: 2023-11-14
• Results First Posted: 2023-11-18
• Last Update Posted: 2023-11-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 52

Inclusion Criteria

• Veterans
• diagnosis of SCH

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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)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo group ("real discontinuation")	Placebo	Stop the current dose of levothyroxine and take study placebo
Levothyroxine group ("sham discontinuation")	Levothyroxine	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score	Baseline, 6 weeks and 6 months	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.
Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score	Baseline, 6 weeks and 6 months	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.
Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6	6 weeks and 6 months	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.
Lipid Levels	6 months	Differences in mean 6-month lipid levels after adjusting for gender and baseline lipid level.

Trial Locations

Locations (1)

Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR; 🇺🇸 North Little Rock, Arkansas, United States