Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism

• Sponsor: VA Office of Research and Development (U.S. Fed)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT04288115
• Collaborator: Central Arkansas Veterans Healthcare System (U.S. Fed)
• Enrollment: 50
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 22
• Patients Per Site Per Month: 2.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Subclinical Hypothyroidism	Drug: Levothyroxine; Other: Placebo	Phase 4

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 scale scores of the 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).

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Discontinuation of Levothyroxine Therapy for Patients With Subclinical Hypothyroidism: a Pilot Randomized, Double-blinded, Placebo-controlled Study
• Actual Study Start Date: Mar 2, 2021
• Actual Primary Completion Date: Apr 8, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
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).	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 Names: Synthroid
Placebo Comparator: Placebo group ("real discontinuation") Stop the current dose of levothyroxine and take study placebo	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.

Outcome Measures

Primary Outcome Measures

1. Participants' willingness to enter the trial [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

2. Recruitment rate [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

3. Completion rate [through study completion, an average of 6 months]

   Percent of randomized participants who completed the trial

Secondary Outcome Measures

1. Change in Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Hypothyroid Symptoms Score [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.

2. Change in Thyroid-specific Quality of Life Patient-Reported Outcome (ThyPRO) - Tiredness score [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.

3. Change in Euro Quality of Life 5-Dimension Self-Report Questionnaire (EQ-5D) score [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.

4. Change in lipid levels [Baseline and 6 months.]

   Changes in score from baseline to 6 months. Positive change/difference is a worse outcome.

Other Outcome Measures

1. Acceptability of intervention: qualitative interview [6 months]

   qualitative interview to provide feedback on experiences

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 89 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Veterans

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

Exclusion Criteria:

• TSH > 10 mlU/L (at any point)

• 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR	North Little Rock	Arkansas	United States	72114-1706

Sponsors and Collaborators

• VA Office of Research and Development
• Central Arkansas Veterans Healthcare System

Investigators

• Principal Investigator: Spyridoula Maraka, MD MS, Central Arkansas Veterans Healthcare System Eugene J. Towbin Healthcare Center, Little Rock, AR

Study Documents (Full-Text)

• Informed Consent Form - Oct 13, 2021

More Information

Publications

None provided.

• Responsible Party: VA Office of Research and Development
• ClinicalTrials.gov Identifier: NCT04288115
• Other Study ID Numbers: PPO 20-056; 1521422
• First Posted: Feb 28, 2020
• Last Update Posted: Jun 29, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Hypothyroidism

Study Results

No Results Posted as of Jun 29, 2022