Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

Overview

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 1) evaluate the feasibility of LT4 discontinuation among veterans with SCH and determine the changes in QoL measures, treatment burden and adverse events, and 2) assess the acceptability of LT4 discontinuation among veterans with SCH and LT4 prescribing clinicians.

Full Title of Study: “Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism: a Pilot Randomized, Double-blinded, Placebo-controlled Study”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: August 31, 2021

Detailed Description

This is a pilot, randomized, double-blind, placebo-controlled trial. Semi-structured interviews, from randomized participants and LT4 prescribers, will be completed at the end of the 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 and Tiredness scores of the ThyPRO-39, EuroQoL 5-Dimension Self-Report Questionnaire, and Treatment Burden Questionnaire) measured at baseline, 6-8 weeks and 6 months and 2) incidence of adverse events (overt hypothyroidism, hyperthyroidism, atrial fibrillation, fractures, acute myocardial infarction, stroke, acute coronary syndrome, heart failure, mortality).

The investigators will assess the acceptability of LT4 discontinuation through semi-structured qualitative interviews with participants and LT4 prescribers at the completion of the clinical trial.

Interventions

  • Drug: Levothyroxine
    • Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.
  • Other: Placebo
    • Participants will be instructed to start the study medication the day after randomization. The study medication will be taken orally once a day.

Arms, Groups and Cohorts

  • Active Comparator: Levothyroxine group (“sham discontinuation”)
    • 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).
  • Placebo Comparator: Placebo group (“real discontinuation”)
    • Stop the current dose of levothyroxine and take study placebo

Clinical Trial Outcome Measures

Primary Measures

  • Participants’ willingness to enter the trial
    • Time Frame: from the date that recruitment opened to the date of the last randomization, an average of 6 months
    • Percent of eligible participants approached who consented to participate during the recruitment phase
  • Recruitment rate
    • Time Frame: from the date that recruitment opened to the date of the last randomization, an average of 6 months
    • The number of randomized participants divided by the length of the recruitment period
  • Completion rate
    • Time Frame: through study completion, an average of 6 months
    • Percent of randomized participants who completed the trial

Secondary Measures

  • Change in Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) – Hypothyroid Symptoms Score
    • Time Frame: Baseline, 6-8 weeks and 6 months.
    • Changes in score from baseline to 6-8 weeks, and from baseline to 6 months. Negative change/difference is a worse outcome.
  • Change in Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) – Tiredness score
    • Time Frame: Baseline, 6-8 weeks and 6 months.
    • Changes in score from baseline to 6-8 weeks, and from baseline to 6 months. Negative change/difference is a worse outcome.
  • Change in Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) score
    • Time Frame: Baseline, 6-8 weeks and 6 months.
    • Changes in score from baseline to 6-8 weeks, and from baseline to 6 months. Negative change/difference is a worse outcome.
  • Change in Treatment Burden Questionnaire (TBQ) score
    • Time Frame: Baseline, 6-8 weeks and 6 months.
    • Changes in score from baseline to 6-8 weeks, and from baseline to 6 months. Positive change/difference is a worse outcome.

Participating in This Clinical Trial

Inclusion Criteria

1. Veterans ages 18-89

2. diagnosis of SCH between January 1, 2009 and December 31, 2019, at the Central Arkansas Veterans Healthcare System (CAVHS).

Exclusion Criteria

1. TSH > 10 mlU/L (at any point)

2. LT4 dose more than 75 mcg daily

3. use of antithyroid medications, amiodarone, tyrosine kinase inhibitors or lithium

4. history of thyroidectomy or radioactive iodine therapy

5. pregnancy or plans for pregnancy in the next 6 months

6. an unstable medical condition that would jeopardize safety or interfere with study participation

7. hospitalization for major illness within the previous 4 weeks

8. acute coronary artery syndrome, acute myocarditis, or pancarditis with the previous 4 weeks

9. receiving services from hospice

10. lack of decision-making capacity

11. terminal medical condition for which life expectancy would be less than 6 months

12. not willing to stop LT4

13. self-reported non-adherence to LT4 therapy

14. abnormal TSH at time of screening for participation (assessed during Baseline Visit)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 89 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Central Arkansas Veterans Healthcare System
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Spyridoula Maraka, MD, MS, Principal Investigator, Central Arkansas Veterans Healthcare System
  • Overall Contact(s)
    • Kate Dishongh, (501) 257-4814, Katherine.Dishongh@va.gov

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