Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

VA Office of Research and Development

Status and phase: Completed; Phase 4

Conditions: Subclinical Hypothyroidism

Treatments: Drug: Levothyroxine; Other: Placebo

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT04288115

1521422 (Other Grant/Funding Number)

PPO 20-056

Details and patient eligibility

About

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.

Full 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).

Enrollment: 52 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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52 participants in 2 patient groups, including a placebo group

Levothyroxine group ("sham discontinuation")

Active Comparator group

Description:

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).

Treatment:

Drug: Levothyroxine

Placebo group ("real discontinuation")

Placebo Comparator group

Description:

Stop the current dose of levothyroxine and take study placebo

Treatment:

Other: Placebo