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HypothyroidismPhase 4NCT07787585

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

A Phase 4 study testing Levothyroxine Pill in people with Hypothyroidism, run by Spyridoula Maraka at 3 sites in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 65 years and older
Conditions the study is for
Hypothyroidism
What is being tested?
Levothyroxine Pill
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
138 participants
Where
3 sitesUnited States
Study dates
Oct 2027to Sep 2031
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • Uncontrolled pain.

Trial locations and contacts

3 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

(501) 257-5848

spyridoula.maraka@va.gov

Katherine Dishongh contact

(501) 507-9554

katherine.dishongh@va.gov

United States3 sites
  • University of Florida Clinical Research Center

    Gainesville, Florida, 32610

    Naykky Singh Ospina, M.D., M.S., (352) 273-8655, naykky.singhospina@medicine.ufl.edu

    Naykky Singh Ospina, M.D., M.S.

  • Central Arkansas Veterans Healthcare System

    Little Rock, Arkansas, 72205

    Spyridoula Maraka, M.D., M.S., (501) 257-5848, spyridoula.maraka@va.gov

    Katherine Dishongh, (501) 507-9554, katherine.dishongh@va.gov

  • Mayo Clinic

    Rochester, Minnesota, 55905

    Juan Pablo Brito Campana, M.B.B.S., (507) 266-0500, brito.juan@mayo.edu

    Juan Pablo Brito Campana, M.B.B.S.

Other trials in United States

About this study

Official title: Discontinuation of Low Dose Levothyroxine Therapy for Older Adults With Subclinical Hypothyroidism: a Randomized, Double-blinded, Placebo-controlled Study

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:

Read more
  • 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
Being tested
Levothyroxine Pill, Placebo
Keywords
subclinical hypothyroidism, levothyroxine, deprescribing, thyroid-related symptoms, older adults
Medical subject headings
Hypothyroidism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Levothyroxine PillDrug

    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.

  • PlaceboDrug

    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.

Study groups in NCT07787585
Study groupRoleWhat they receive
Levothyroxine ContinuationActive comparatorParticipants will continue their pre-study dose of levothyroxine for 6 months using blinded study medication.
Receives: Drug: Levothyroxine Pill
Levothyroxine DiscontinuationExperimentalParticipants will discontinue levothyroxine and receive matching placebo for 6 months using blinded study medication.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 6 months

Secondary outcomes (24)
  1. Mean ThyPRO Hypothyroid Symptoms Scale Score Over Time

    Mean score on the 4-item ThyPRO Hypothyroid Symptoms Score. Scores range from 0 to 100, with higher scores indicating more severe hypothyroid symptoms. Longitudinal changes will be evaluated between treatment groups.

    Measured: Baseline, 2 months, 6 months

  2. Mean ThyPRO Tiredness Scale Score

    Tiredness will be assessed using the 7-item ThyPRO Tiredness Scale. Scores range from 0 to 100, with higher scores indicating greater tiredness. Mean scores and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 month, and 6 months

  3. Mean Brief Fatigue Inventory Score

    Fatigue will be assessed during the 9-item Brief Fatigue Inventory (BFI). Items are scored from 0 to 10 and the mean item score will be calculated, with higher scores indicating greater fatigue severity or interference. Mean scores and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  4. Mean Patient-Generated Index Visual Analogue Scale Score

    Participant-identified symptoms considered important and related to subclinical hypothyroidism will be assessed using the Patient-Generated Index (PGI) visual analogue scale. Scores range from 0-100, with higher scores indicating less severe symptoms. Mean scores and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  5. Mean ThyPRO-39 Quality-of-Life Score

    Thyroid-specific quality of life will be assessed using the 39-item ThyPRO-39 questionnaire. Scores range from 0 to 100, with higher scores indicating worse thyroid-related quality of life. Mean scores will be compared between treatment groups.

    Measured: Baseline and 6 months

  6. Mean EQ-5D Descriptive Index Score

    General health-related quality of life will be assessed using the EQ-5D descriptive index. Scores range from -0.59 to 1.00, with higher scores indicating better health-related quality of life. Mean scores and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  7. Mean EQ Visual Analogue Scale Score

    Self-rated health will be assessed using the EQ visual analogue scale (EQ VAS). Scores range from 0 to 100, with higher scores indicating better self-rated health. Mean scores and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  8. Number of Participants Preferring Study Treatment Versus Pre-Study Treatment

    Participants will report whether they prefer the treatment they are currently receiving during the study or their pre-study levothyroxine treatment. The number and percentage of participants reporting each preference will be summarized by treatment group.

    Measured: 2 months and 6 months

  9. Mean Modified Telephone Interview for Cognitive Status Score

    Cognitive function will be assessed using the Modified Telephone Interview for Cognitive Status (TICS-M), a 13-item cognitive assessment evaluating orientation, concentration, memory, naming, calculation, comprehension, and reasoning. Total scores range from 0 to 39, with higher scores indicating better cognitive performance. Mean scores will be compared between treatment groups.

    Measured: Baseline and 6 months

  10. Mean Body Weight

    Body weight will be measured in kilograms. Mean body weight and change in body weight will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  11. Mean Thyroid-Stimulating Hormone Level

    Serum thyroid-stimulating hormone (TSH) will be measured in mIU/L to assess thyroid function. Mean TSH levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  12. Mean Free Thyroxine Level

    Serum free thyroxine (free T4) will be measured in ng/dL to assess thyroid function. Mean free T4 levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  13. Mean Total Cholesterol Level

    Serum total cholesterol will be measured in mg/dL. Mean levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  14. Mean Low-Density Lipoprotein Cholesterol Level

    Serum low-density lipoprotein (LDL) cholesterol will be measured in mg/dL. Mean levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  15. Mean High-Density Lipoprotein Cholesterol Level

    Serum high-density lipoprotein (HDL) cholesterol will be measured in mg/dL. Mean levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  16. Mean Triglyceride Level

    Serum triglycerides will be measured in mg/dL. Mean levels and longitudinal changes will be compared between treatment groups.

    Measured: Baseline, 2 months, and 6 months

  17. Incidence of All-Cause Mortality

    Number and proportion of participants who die from any cause during study participation, assessed through medical record review and/or family report.

    Measured: From enrollment to the end of the study at 6 months

  18. Incidence of Cardiovascular Events

    Number and proportion of participants experiencing one or more cardiovascular events, including acute myocardial infarction, atrial fibrillation, stroke, acute coronary syndrome, or heart failure, assessed through medical record review and participant report.

    Measured: From enrollment to the end of the study at 6 months

  19. Incidence of Falls and Fractures

    Number and proportion of participants experiencing one or more falls or fractures, assessed through medical record review and participant report.

    Measured: From enrollment to the end of the study at 6 months

  20. Incidence of Overt Hypothyroidism

    Number and proportion of participants who develop overt hypothyroidism based on protocol-defined thyroid hormone criteria.

    Measured: 2 months and 6 months

  21. Incidence of Hyperthyroidism

    Number and proportion of participants who develop hyperthyroidism based on protocol-defined thyroid hormone criteria.

    Measured: 2 months and 6 months

  22. Proportion of Participants Maintaining Euthyroid Status After Levothyroxine Discontinuation

    Among participants randomized to levothyroxine discontinuation/placebo, the number and proportion who remain euthyroid based on protocol-defined thyroid hormone criteria will be assessed.

    Measured: 2 months and 6 months

  23. Number of Participants with Adverse Events

    Number and proportion of participants experiencing one or more adverse events during study participation. Adverse events will be assessed and classified according to the protocol-defined criteria for severity, expectedness, and relationship to study intervention.

    Measured: From enrollment to 30 days after Month 6

  24. Number of Participants with Serious Adverse Events

    Number and proportion of participants experiencing one or more serious adverse events as defined in the study protocol.

    Measured: From enrollment to 30 days after Month 6

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Aug 2026
  2. Study startOct 2027 (estimated)
  3. Primary completionSep 2030 (estimated)
  4. Study completionSep 2031 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
138 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07787585
Sponsor's protocol ID
LT4-DISCONTINUE-01
Status last verified
Aug 2026
First submitted
11 Aug 2026
Last updated
26 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Levothyroxine Pill in people with Hypothyroidism, run by Spyridoula Maraka at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Spyridoula Maraka, M.D., M.S. ((501) 257-5848, spyridoula.maraka@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean ThyPRO Hypothyroid Symptoms Scale Score at 6 Months (time frame: 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.

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