NCT04288115

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
52

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Mar 2021

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

February 14, 2020

Completed
14 days until next milestone

First Posted

Study publicly available on registry

February 28, 2020

Completed
1.1 years until next milestone

Study Start

First participant enrolled

March 24, 2021

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 7, 2022

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2022

Completed
11 months until next milestone

Results Posted

Study results publicly available

November 18, 2023

Completed
Last Updated

November 18, 2023

Status Verified

November 1, 2023

Enrollment Period

1.5 years

First QC Date

February 14, 2020

Results QC Date

September 27, 2023

Last Update Submit

November 14, 2023

Conditions

Subclinical Hypothyroidism

Outcome Measures

Primary Outcomes (3)

  • 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 Outcomes (4)

  • Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score

    Baseline, 6 weeks and 6 months

  • Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness Score

    Baseline, 6 weeks and 6 months

  • Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) Score at Week 6 and Month 6

    6 weeks and 6 months

  • Lipid Levels

    6 months

Study Arms (2)

Levothyroxine group ("sham discontinuation")

ACTIVE COMPARATOR

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

Placebo group ("real discontinuation")

PLACEBO COMPARATOR

Stop the current dose of levothyroxine and take study placebo

Other: Placebo

Interventions

LevothyroxineDRUG

Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.

Also known as: Synthroid
Levothyroxine group ("sham discontinuation")
PlaceboOTHER

Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.

Placebo group ("real discontinuation")

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Veterans
  • diagnosis of SCH

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

North Little Rock, Arkansas, 72114-1706, United States

Location

Related Publications (9)

  • Brito JP, Ross JS, El Kawkgi OM, Maraka S, Deng Y, Shah ND, Lipska KJ. Levothyroxine Use in the United States, 2008-2018. JAMA Intern Med. 2021 Oct 1;181(10):1402-1405. doi: 10.1001/jamainternmed.2021.2686.

    PMID: 34152370BACKGROUND

  • Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, Ford I, Gussekloo J, Kearney PM, Mooijaart S, Quinn T, Stott D, Westendorp R, Rodondi N, Dekkers OM. Association of Thyroid Hormone Therapy With Quality of Life and Thyroid-Related Symptoms in Patients With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis. JAMA. 2018 Oct 2;320(13):1349-1359. doi: 10.1001/jama.2018.13770.

    PMID: 30285179BACKGROUND

  • Stott DJ, Rodondi N, Kearney PM, Ford I, Westendorp RGJ, Mooijaart SP, Sattar N, Aubert CE, Aujesky D, Bauer DC, Baumgartner C, Blum MR, Browne JP, Byrne S, Collet TH, Dekkers OM, den Elzen WPJ, Du Puy RS, Ellis G, Feller M, Floriani C, Hendry K, Hurley C, Jukema JW, Kean S, Kelly M, Krebs D, Langhorne P, McCarthy G, McCarthy V, McConnachie A, McDade M, Messow M, O'Flynn A, O'Riordan D, Poortvliet RKE, Quinn TJ, Russell A, Sinnott C, Smit JWA, Van Dorland HA, Walsh KA, Walsh EK, Watt T, Wilson R, Gussekloo J; TRUST Study Group. Thyroid Hormone Therapy for Older Adults with Subclinical Hypothyroidism. N Engl J Med. 2017 Jun 29;376(26):2534-2544. doi: 10.1056/NEJMoa1603825. Epub 2017 Apr 3.

    PMID: 28402245BACKGROUND

  • Bekkering GE, Agoritsas T, Lytvyn L, Heen AF, Feller M, Moutzouri E, Abdulazeem H, Aertgeerts B, Beecher D, Brito JP, Farhoumand PD, Singh Ospina N, Rodondi N, van Driel M, Wallace E, Snel M, Okwen PM, Siemieniuk R, Vandvik PO, Kuijpers T, Vermandere M. Thyroid hormones treatment for subclinical hypothyroidism: a clinical practice guideline. BMJ. 2019 May 14;365:l2006. doi: 10.1136/bmj.l2006.

    PMID: 31088853BACKGROUND

  • Ayala IN, Soto Jacome C, Toro-Tobon D, Golembiewski E, Garcia-Bautista A, Hidalgo J, Cordova-Madera S, Al Anbari R, Sohn R J, Singh Ospina N, Maraka S, Joseph M, Brito JP. Appropriateness of Levothyroxine Prescription: A Multicenter Retrospective Study. J Clin Endocrinol Metab. 2024 Jan 18;109(2):e765-e772. doi: 10.1210/clinem/dgad517.

    PMID: 37656124BACKGROUND

  • Toloza FJK, El Kawkgi OM, Spencer HJ, Mathews SE, Garcia A, Gamboa A, Mirza N, Mohan S, Vallejo S, Bogojevic M, Rodriguez-Gutierrez R, Singh Ospina NM, Brito JP, Maraka S. Determinants for Thyroid Hormone Replacement Therapy in Subclinical Hypothyroidism: A Multicenter Electronic Health Records-Based Study. Thyroid. 2023 Sep;33(9):1045-1054. doi: 10.1089/thy.2023.0062. Epub 2023 Jun 26.

    PMID: 37279296BACKGROUND

  • Ospina NS, Salloum RG, Maraka S, Brito JP. De-implementing low-value care in endocrinology. Endocrine. 2021 Aug;73(2):292-300. doi: 10.1007/s12020-021-02732-y. Epub 2021 May 11.

    PMID: 33977312BACKGROUND

  • Burgos N, Toloza FJK, Singh Ospina NM, Brito JP, Salloum RG, Hassett LC, Maraka S. Clinical Outcomes After Discontinuation of Thyroid Hormone Replacement: A Systematic Review and Meta-Analysis. Thyroid. 2021 May;31(5):740-751. doi: 10.1089/thy.2020.0679. Epub 2020 Dec 29.

    PMID: 33161885BACKGROUND

  • Maraka S, Owen RR, Singh Ospina NM, Knox M, Dodds T, Thostenson JD, Dishongh K, Raciborski RA, Albashaireh A, Shah A, Syed S, Naqvi S, Motahari H, Thumma S, Toloza F, Ambrogini E, Brito JP. Discontinuation of levothyroxine therapy in patients with subclinical hypothyroidism: a pilot randomized clinical trial. Endocrine. 2025 Nov;90(2):781-792. doi: 10.1007/s12020-025-04371-z. Epub 2025 Jul 30.

    PMID: 40736623DERIVED

MeSH Terms

Interventions

Thyroxine

Intervention Hierarchy (Ancestors)

Thyroid HormonesHormonesHormones, Hormone Substitutes, and Hormone AntagonistsAmino Acids, AromaticAmino Acids, CyclicAmino AcidsAmino Acids, Peptides, and Proteins

Results Point of Contact

Title
Spyridoula Maraka, MD, MS
Organization
Central Arkansas Veterans Healthcare System
Spyridoula.Maraka@va.gov
(501) 257-5848

Study Officials

  • Spyridoula Maraka, MD MS

    Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 14, 2020

First Posted

February 28, 2020

Study Start

March 24, 2021

Primary Completion

October 7, 2022

Study Completion

December 31, 2022

Last Updated

November 18, 2023

Results First Posted

November 18, 2023

Record last verified: 2023-11

Data Sharing

IPD Sharing
Will not share

Locations

US(1)