A Randomized Controlled Trial of Thyroid Hormone Supplementation in Hemodialysis Patients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

336 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-20

Study Completion Date

2025-11-30

Brief Summary

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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.

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Detailed Description

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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 impaired health-related quality of life (HRQOL) and cardiovascular (CV) morbidity and mortality, but until recently there was a paucity of data regarding its prognostic implications in CKD. Our research has been 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). Our studies have also advanced the field by showing that elevated TSH levels even within the "normal" range (\>3.0mIU/L) are associated with heightened risk of CV disease and death across multiple dialysis cohorts. 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. While levothyroxine is one of the most commonly prescribed medications in CKD, little is known about its efficacy in this population.

To address these knowledge gaps, we propose to conduct a randomized double-blind placebo-controlled trial among 336 hemodialysis patients with high-normal or subclinical hypothyroid range serum TSH levels to determine the effects of 24 weeks (i.e., 6 months) of levothyroxine vs. placebo on 1) HRQOL Short Form 36 (SF36) Physical Component Score and 2) coronary artery calcifcation (CAC) progression (co-primary endpoints).

As secondary endpoints, we will also examine 1) HRQOL measured by the ThyPRO survey, 2) physical performance, 3) endothelial function, 4) vascular calcification inhibitor levels, and 5) total body fat percentage. In a sub-study of 108 hemodialysis patients, we will also examine exploratory secondary endpoints of 1) muscle strength, 2) systolic function, and 3) resting energy expenditure.

Conditions

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Thyroid; Functional Disturbance Hypothyroidism Hemodialysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Levothyroxine Sodium

Intervention Type DRUG

Thyroid hormone supplement

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.

Group Type PLACEBO_COMPARATOR

Placebos

Intervention Type DRUG

Placebo oral capsule

Interventions

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Levothyroxine Sodium

Thyroid hormone supplement

Intervention Type DRUG

Placebos

Placebo oral capsule

Intervention Type DRUG

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No