# A Randomized Controlled Trial of Thyroid Hormone Supplementation in Hemodialysis Patients

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA-IRVINE · 2022 · $680,132

## Abstract

PROJECT SUMMARY/ABSTRACT
 Data spanning over three decades show that hypothyroidism is highly prevalent in the chronic kidney
disease (CKD) population, affecting 25% of those receiving dialysis therapy. In the general population
hypothyroidism, defined by elevated thyrotropin (TSH) levels, has been associated with cardiovascular (CV)
morbidity and mortality and impaired health-related quality of life (HRQOL), but until recently there was a
paucity of data regarding its prognostic implications in CKD. Our pioneering studies supported by the PI’s NIH
F32, K23, and R03 awards have advanced the field by showing that elevated thyrotropin (TSH) levels even
within the “normal” range (>3.0mIU/L) are associated with heightened risk of CV disease (e.g., coronary artery
calcification, endothelial dysfunction) and death across multiple dialysis cohorts. With support of an American
Thyroid Association grant, our research was also the first to show a link between high-normal TSH levels and
worse HRQOL Short Form 36 scores in dialysis patients, particularly among subscales centered on physical
health (e.g., physical function, energy/fatigue). However, there remains considerable controversy as to 1)
whether thyroid dysfunction is causally associated with adverse patient-centered and CV outcomes, and 2) if
elevated TSH levels represent thyroid functional disease vs. non-thyroidal illness in CKD. Moreover, as United
States Renal Data System analyses show that levothyroxine (L-T4) is one of the most commonly prescribed
medications in end-stage renal disease patients, there is pressing urgency for a randomized controlled trial
(RCT) that will determine the efficacy and safety of L-T4 in this population.
 In the spirit of our recent discoveries and supportive findings by others, we propose this R01 study in
which an Early-Stage Investigator, complemented by a uniquely well-qualified multi-disciplinary team of
experts, will conduct a rigorously-designed and feasible randomized, double-blind, parallel two-arm trial of L-T4
vs. placebo among 336 hemodialysis patients with high-normal or subclinical hypothyroid TSH levels (>3.0-5.0
and >5.0-10.0mIU/L, respectively). Our primary objective will be to determine the effects of six months of L-T4
on the co-primary outcomes of HRQOL (Aim 1) and coronary artery calcification (Aim 2). Our main secondary
objectives will be to determine the effects of L-T4 on the domains of physical performance (Aim 1), vascular
health (Aim 2), and body composition (Aim 3). In a subcohort of 108 HD patients from the parent trial, we will
also examine the effects of L-T4 on three novel exploratory secondary endpoints of muscle strength, cardiac
function, and resting energy expenditure that will inform the framework of future multi-center corollary RCT’s.
Successful completion of this R01 proposal will address major knowledge gaps by determining whether thyroid
dysfunction is a novel, modifiable risk factor for impaired HRQOL and CV disease in CKD; ...

## Key facts

- **NIH application ID:** 10438772
- **Project number:** 5R01DK122767-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Connie Meeyoung Rhee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $680,132
- **Award type:** 5
- **Project period:** 2019-07-09 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438772

## Citation

> US National Institutes of Health, RePORTER application 10438772, A Randomized Controlled Trial of Thyroid Hormone Supplementation in Hemodialysis Patients (5R01DK122767-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438772. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*