Recruiting

Thyroid Hormone

Sponsor:

UCLA

Code:

NCT03977207

Conditions

Thyroid; Functional Disturbance

Hypothyroidism

Hemodialysis

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Levothyroxine Sodium

Placebos

Study Details

Brief summary:

Hypothyroidism, defined by elevated thyrotropin (TSH) levels, is a common endocrine complication in chronic kidney disease patients, and prior evidence shows that higher TSH levels, even within the normal laboratory range, are strongly associated with impaired quality of life and cardiovascular disease in this population. Levothyroxine is one of the most frequently prescribed medications in chronic kidney disease, yet its efficacy and safety in these patients have not been well-studied. Hence, this study will investigate 1) whether levothyroxine improves patient-centered (e.g., health-related quality of life, physical performance, strength) and 2) cardiovascular (e.g., coronary artery calcification, endothelial function, systolic function) outcomes in dialysis patients, and 3) if thyroid hormone replacement exerts classic metabolic effects (i.e., changes in body fat and resting energy expenditure) in this population.

Conditions

Thyroid; Functional Disturbance

Hypothyroidism

Hemodialysis

Study ID

NCT03977207

Start date

Jul 20, 2020

Status verified date

Aug, 2025

Completion date

Nov 30, 2025

Anticipated

Primary completion date

Nov 30, 2025

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 18-75 years old
  • Received hemodialysis at least four weeks
  • Have two consecutive thyrotropin (TSH) levels >3.0-10.0mIU/L during the screening period
  • Have normal free thyroxine (FT4) levels
  • Have ability to provide written informed consent

Exclusion Criteria:

  • Active treatment with thyroid hormone supplementation or anti-thyroid medications
  • Active receipt of dialysis
  • Prior kidney transplantation
  • Life expectancy less than six months
  • Active malignancy or prior thyroid malignancy
  • Active pregnancy or planning a pregnancy
  • Active coronary ischemia or atrial fibrillation (evaluated by EKG)
  • Active congestive heart failure exacerbation
  • Osteoporosis
  • Weight in excess of 450 lbs.
  • Hyperthyroidism as determined by TSH <0.5mIU/L during the screening period, anti-thyroid medication use, or hyperthyroidism diagnosis

Study Design

Enrollment

336 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Levothyroxine

Patients will be randomized to levothyroxine or placebo (similar in size, shape, and color to levothyroxine) via permuted blocks stratified by two TSH levels (>3.0-5.0 and 5.0-10.0mIU/L) to ensure treatment balance across TSH levels. The study medications will be prepared in pill form. In the treatment arm, initial L-T4 doses will be 25mcg vs. 50mcg among patients whose TSH is >3.0-5.0mIU/L vs. 5.0-10.0mIU/L, respectively. Patients in the placebo arm will receive an equivalent number of placebo pills daily depending upon TSH level.

The intervention period is 24 weeks. Patients will undergo up to two subsequent dose titrations after 8- and 16-weeks of treatment, based on interim TSH measurements at these time points. Patients whose TSH levels are higher or lower than the therapeutic TSH target of 0.5-3.0mIU/L will undergo a dose adjustment (+/- 25mcg), while those whose TSH levels are in target range will continue the prior dose.

placebo comparator: Placebo

Patients will be randomized to levothyroxine or placebo (similar in size, shape, and color to levothyroxine) via permuted blocks stratified by two TSH levels (>3.0-5.0 and 5.0-10.0mIU/L) to ensure treatment balance across TSH levels. The study medications will be prepared in pill form. In the treatment arm, initial L-T4 doses will be 25mcg vs. 50mcg among patients whose TSH is >3.0-5.0mIU/L vs. 5.0-10.0mIU/L, respectively. Patients in the placebo arm will receive an equivalent number of placebo pills daily depending upon TSH level.

The intervention period is 24 weeks. Patients in the placebo arm will undergo an equivalent titration in placebo pills (as that of the experimental arm) after 8- and 16-weeks of treatment, based on interim TSH measurements at these time points.

Interventions

Levothyroxine Sodium

Thyroid hormone supplement

Placebos

Placebo oral capsule

Primary outcome measure

  • Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score [ Time Frame: Week 0 (pre-trial/baseline) ]
  • Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score [ Time Frame: Week 12 ]
  • Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score [ Time Frame: Week 24 ]
  • Coronary Artery Calcification (CAC) - Volume Score [ Time Frame: Week 0 (pre-trial/baseline) ]
  • Coronary Artery Calcification (CAC) - Volume Score [ Time Frame: Week 24 ]

Central Contacts and Locations

Central contacts

Connie Rhee, MD, MSc

714-456-5142crhee1@uci.edu

Locations

University of California Irvine

Recruiting

Orange, California, United States, 92868

Contacts

Kamyar Kalantar-Zadeh

7144565142kkz@uci.edu

More Information

Sponsor

University of California, Irvine

Last update posted

Sep 8, 2025

Last verified

Aug, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by University of California, Irvine on 2025-09-08.