Discontinuation of Low-Dose Levothyroxine in Older Adults With Subclinical Hypothyroidism

NCT07787585 | Not Yet Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: LT4-DISCONTINUE-01
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 3

Brief Summary

The goal of this clinical trial is to learn whether low-dose levothyroxine can be safely discontinued in adults aged 65 years or older who are taking levothyroxine for subclinical hypothyroidism. The study will also evaluate the cost-effectiveness of discontinuing levothyroxine. The main questions it aims to answer are:

• Does discontinuing levothyroxine result in no clinically meaningful worsening of thyroid-related symptoms compared with continuing levothyroxine?
• What are the effects of discontinuing levothyroxine on quality of life, tiredness, cognition, thyroid hormone levels, lipid levels, weight, and adverse events?
• Is discontinuing levothyroxine cost-effective compared with continuing treatment? Researchers will compare participants who discontinue levothyroxine and receive placebo with participants who continue their current dose of levothyroxine to determine the effects of levothyroxine discontinuation. Participants will:
• Complete a 2-week run-in period during which they continue their usual levothyroxine and record their medication use.
• Eligible participants will be randomly assigned to either continue their current dose of levothyroxine or receive a matching placebo for 6 months. Participants, their clinicians, and study investigators will not know which treatment they are receiving during the study.
• Complete study assessments at baseline, approximately 2 months, and 6 months. Assessments will include blood tests, measurements such as body weight, questionnaires about thyroid-related symptoms and quality of life, and assessments of cognition and other health outcomes.

Conditions

Hypothyroidism

Keywords

subclinical hypothyroidism; levothyroxine; deprescribing; thyroid-related symptoms; older adults

Outcome Measures

Primary Outcomes (1)

• Mean ThyPRO Hypothyroid Symptoms Scale Score at 6 Months

  Thyroid-related symptoms will be assessed using the 4-item Thyroid-specific Patient Reported Outcome (ThyPRO) Hypothyroid Symptoms Scale. Scores are transformed to a 0-100 scale, with higher scores indicating more severe hypothyroid symptoms. The mean 6-month score will be compared between the levothyroxine discontinuation (placebo) group and the levothyroxine continuation group. The prespecified noninferiority margin is 9 points.

  6 months

Secondary Outcomes (24)

• Mean ThyPRO Hypothyroid Symptoms Scale Score Over Time

  Baseline, 2 months, 6 months

• Mean ThyPRO Tiredness Scale Score

  Baseline, 2 month, and 6 months

• Mean Brief Fatigue Inventory Score

  Baseline, 2 months, and 6 months

• Mean Patient-Generated Index Visual Analogue Scale Score

  Baseline, 2 months, and 6 months

• Mean ThyPRO-39 Quality-of-Life Score

  Baseline and 6 months

Study Arms (2)

Levothyroxine Continuation

ACTIVE COMPARATOR

Participants will continue their pre-study dose of levothyroxine for 6 months using blinded study medication.

Drug: Levothyroxine Pill

Levothyroxine Discontinuation

EXPERIMENTAL

Participants will discontinue levothyroxine and receive matching placebo for 6 months using blinded study medication.

Drug: Placebo

Interventions

Levothyroxine Pill DRUG

Participants assigned to the levothyroxine continuation arm will continue levothyroxine at their pre-study dose (≤50 mcg/day) for 6 months. Levothyroxine will be administered orally once daily as over-encapsulated study medication matched in appearance to placebo to maintain blinding.

Levothyroxine Continuation

Placebo DRUG

Participants assigned to the levothyroxine discontinuation arm will discontinue levothyroxine and receive matching placebo orally once daily for 6 months. Placebo will be over-encapsulated and matched in appearance to the active study medication to maintain blinding.

Levothyroxine Discontinuation

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Age ≥65 years.
• Euthyroid at the time of enrollment, defined as thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels within the reference range.
• Receiving levothyroxine treatment for subclinical hypothyroidism for at least 6 months.
• Receiving levothyroxine at a dose ≤50 mcg/day, or ≤25 mcg/day for participants weighing \<50 kg.
• Receiving outpatient care at the participating study site for at least 12 months.
• Subclinical hypothyroidism is defined as a TSH level above the normal reference range but \<10 mIU/L, with a normal fT4 level, prior to initiation of levothyroxine therapy.

You may not qualify if:

• TSH \>10 mIU/L at any time documented in the institutional electronic health record.
• Levothyroxine therapy initiated less than 6 months before enrollment.
• Abnormal thyroid function at the time of enrollment.
• Current use of medications that affect thyroid hormone levels, such as antithyroid medications, amiodarone, or lithium.
• History of thyroid cancer or goiter with compressive symptoms.
• History of partial or total thyroidectomy or radioactive iodine therapy.
• New York Heart Association (NYHA) Class IV heart failure.
• Hospitalization for a major illness or elective surgery within the previous 4 weeks, including acute coronary syndrome, acute myocarditis, pancarditis, or stroke.
• Unstable medical condition that, in the investigator's judgment, would jeopardize participant safety or interfere with study participation.
• Terminal illness with a life expectancy of less than 6 months.
• Lack of decision-making capacity.
• Severe dyslipidemia, defined as LDL cholesterol \>190 mg/dL.
• Untreated depression.
• Uncontrolled psychiatric disorder.
• Uncontrolled chronic fatigue syndrome.

Sponsors & Collaborators

• Spyridoula Maraka: lead

Study Sites (3)

Central Arkansas Veterans Healthcare System

Little Rock, Arkansas, 72205, United States

Location

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Hypothyroidism

Interventions

Thyroxine

Condition Hierarchy (Ancestors)

Thyroid Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thyroid Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Spyridoula Maraka, M.D., M.S.

  Central Arkansas Veterans Healthcare System

  STUDY DIRECTOR

Central Study Contacts

Spyridoula Maraka, M.D., M.S.

CONTACT

(501) 257-5848; spyridoula.maraka@va.gov

Katherine Dishongh

CONTACT

(501) 507-9554; katherine.dishongh@va.gov

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Program Director/Principal Investigator

Study Record Dates

• First Submitted: August 11, 2026
• First Posted: August 26, 2026
• Study Start (Estimated): October 1, 2027
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2031
• Last Updated: August 26, 2026

Record last verified: 2026-08

Locations

US (3)