A Randomized Controlled Trial of Thyroid Hormone Supplementation in Hemodialysis Patients

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-75
SponsorUniversity of California, Irvine

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Active treatment with thyroid hormone supplementation or anti-thyroid medications

Active receipt of dialysis

Prior kidney transplantation

Life expectancy less than six months

Trial design

Design model

Parallel

Treatments tested in this trial

  • Levothyroxine Sodium

    Drug

    Thyroid hormone supplement

  • Placebos

    Drug

    Placebo oral capsule

Treatment groups

336 Participants
are divided into 2 treatment groups
Group A: LevothyroxineExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score

We will assess HRQOL using the Short Form 36, which consists of 36 questions grouped into eight subscales (score 0-100 for each subscale; higher scores indicate better states of health) that will be used to derive a summary Physical Component Score.

Time frame
Week 0 (pre-trial/baseline)
2

Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score

We will assess HRQOL using the Short Form 36, which consists of 36 questions grouped into eight subscales (score 0-100 for each subscale; higher scores indicate better states of health) that will be used to derive a summary Physical Component Score.

Time frame
Week 12
3

Health-Related Quality of Life (HRQOL) - Short Form 36 Physical Component Score

We will assess HRQOL using the Short Form 36, which consists of 36 questions grouped into eight subscales (score 0-100 for each subscale; higher scores indicate better states of health) that will be used to derive a summary Physical Component Score.

Time frame
Week 24
4

Coronary Artery Calcification (CAC) - Volume Score

We will assess CAC Volume Score using a 256-multidetector CT test. Volume score will be calculated by multiplying the number of voxels with calcification by the volume of each voxel for each calcified lesion, and summing individual lesion scores from the four main coronary arteries (left main, left anterior descending, circumflex, and right coronary artery).

Time frame
Week 0 (pre-trial/baseline)

Secondary outcomes

1

Thyroid-Specific HRQOL - ThyPRO Hypothyroid Symptoms and Tiredness Domain Scores

We will administer the thyroid-specific quality of life patient-reported outcome (ThyPRO) measure, which is comprised of 84 items categorized into 13 domains, plus a general quality of life question (this is a composite measure).

Time frame
Weeks 0 (pre-trial/baseline) and 24 (post-randomization)
2

Physical Performance - Short Physical Performance Battery (SPPB)

We will measure physical performance using the Short Physical Performance Battery (SPPB), which tests 1) gait speed (faster of two timed, usual pace 15-foot walks), 2) balance (balance test measuring ability to stand with feet in side-by-side, semi-tandem, and tandem positions for 10 seconds), and 3) chair raises (timed series of five attempts to arise from a chair unassisted without use of arms), with each component ranging from 0 to 4 (score 0-12; higher score indicates better performance).

Time frame
Weeks 0 (pre-trial/baseline) and 24 (post-randomization)
3

Endothelial Function - Digital Thermal Monitor

We will measure endothelial function using digital thermal monitor (DTM) testing, which is based on the principle that changes in fingertip temperature during and after an ischemic stimulus (blood pressure \[BP\] cuff occlusion) reflect changes in blood flow. In normal endothelial function, cuff inflation results in a 1-3 degree Celsius temperature decline, followed by rapid temperature rise to above baseline during cuff deflation due to compensatory vasodilation. Temperature (temp) will be measured before, during, and after a 2-minute BP cuff inflation in the non-vascular access arm in order to measure Area Under the Temp Curve (TMP-AUC), defined as area under the curve between the maximum and minimum temp.

Time frame
Weeks 0 (pre-trial/baseline) and 24 (post-randomization)
4

Vascular Calcification Inhibitor - Matrix Gla Protein Levels

We will use plasma collected during hemodialysis treatments to measure total uncarboxylated matrix Gla protein levels. Assays will be conducted in the University of California Irvine Institute of Clinical Translational Science Bioassay Core.

Time frame
Weeks 0 (pre-trial/baseline) and 24 (post-randomization)

Other outcomes

Sponsors and contacts

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University of California, Irvine

Lead sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator