A Pilot Feasibility Trial of Thyroid Hormone Replacement in Dialysis Patients

Hypothyroidism, defined by elevated thyrotropin (TSH) levels, is a common endocrine complication of chronic kidney disease that has been associated with impaired quality of life and cardiovascular complications. While levothyroxine is one of the most frequently prescribed medications in chronic kidney disease patients, little is known about its efficacy and safety in this population. This study will investigate 1) whether levothyroxine adequately lowers thyrotropin (TSH) levels to therapeutic target ranges, and 2) if thyroid hormone replacement improves quality of life and cardiovascular markers, without leading to wasting in dialysis patients.

Study Overview

• Status: Recruiting
• Conditions: Thyroid Disease; Kidney Diseases, Chronic
• Intervention / Treatment: Drug: Placebo Oral Tablet; Drug: Levothyroxine Sodium

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Connie M. Rhee, MD, MSc; Phone Number: 714-456-5142; Email: crhee1@uci.edu

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • Recruiting
      • University Dialysis Center of Orange
      • Contact: Kamyar Kalantar-Zadeh, MD, MPH, PhD; Phone Number: 714-634-3583; Email: kkz@uci.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Prevalent hemodialysis patients, elevated thyrotropin level, normal free thyroxine level.

Exclusion Criteria:

• Hyperthyroidism, active treatment with thyroid hormone replacement, prior thyroid malignancy, active pregnancy, active coronary ischemia or atrial fibrillation, osteoporosis, inability to provide consent without a proxy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo Oral Tablet; Placebo
EXPERIMENTAL: Levothyroxine	Drug: Levothyroxine Sodium; Thyroid hormone supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Achievement of target TSH levels: serum TSH levels ranging from 0.5-3.0mIU/L	Number of patients achieving target TSH levels of 0.5-3.0mIU/L	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Health-related quality of life Short Form 36 questionnaire	Change in Short Form 36 score	Baseline and 12 weeks
Serum Growth Differentiation Factor 15 (GDF15) level	Change in GDF15 level	Baseline and 12 weeks
Serum soluble p-selectin level	Change in soluble p-selectin level	Baseline and 12 weeks
Serum soluble CD40 ligand level	Change in serum soluble CD40 ligand level	Baseline and 12 weeks
Body mass index	Change in body mass index	Baseline and 12 weeks
Biceps skinfold	Change in biceps skinfold	Baseline and 12 weeks
Triceps skinfold	Change in triceps skinfold	Baseline and 12 weeks
Mid-arm circumference	Change in mid-arm circumference	Baseline and 12 weeks
Mid-arm muscle circumference	Change in mid-arm muscle circumference	Baseline and 12 weeks
Near infrared body fat percentage	Change in near infrared body fat percentage	Baseline and 12 weeks
Subjective Global Assessment questionnaire	Subjective Global Assessment questionnaire score	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: University of California, Irvine
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Connie M. Rhee, MD, MSc, University of California, Irvine

Publications and helpful links

General Publications

• Rhee CM, You AS, Nguyen DV, Brunelli SM, Budoff MJ, Streja E, Nakata T, Kovesdy CP, Brent GA, Kalantar-Zadeh K. Thyroid Status and Mortality in a Prospective Hemodialysis Cohort. J Clin Endocrinol Metab. 2017 May 1;102(5):1568-1577. doi: 10.1210/jc.2016-3616.
• Rhee CM, Kim S, Gillen DL, Oztan T, Wang J, Mehrotra R, Kuttykrishnan S, Nguyen DV, Brunelli SM, Kovesdy CP, Brent GA, Kalantar-Zadeh K. Association of thyroid functional disease with mortality in a national cohort of incident hemodialysis patients. J Clin Endocrinol Metab. 2015 Apr;100(4):1386-95. doi: 10.1210/jc.2014-4311. Epub 2015 Jan 29.
• Rhee CM, Ravel VA, Streja E, Mehrotra R, Kim S, Wang J, Nguyen DV, Kovesdy CP, Brent GA, Kalantar-Zadeh K. Thyroid Functional Disease and Mortality in a National Peritoneal Dialysis Cohort. J Clin Endocrinol Metab. 2016 Nov;101(11):4054-4061. doi: 10.1210/jc.2016-1691. Epub 2016 Aug 15.
• Rhee CM, Kalantar-Zadeh K, Streja E, Carrero JJ, Ma JZ, Lu JL, Kovesdy CP. The relationship between thyroid function and estimated glomerular filtration rate in patients with chronic kidney disease. Nephrol Dial Transplant. 2015 Feb;30(2):282-7. doi: 10.1093/ndt/gfu303. Epub 2014 Sep 21.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ANTICIPATED): July 1, 2021
• Study Completion (ANTICIPATED): July 1, 2021

Study Registration Dates

• First Submitted: June 13, 2017
• First Submitted That Met QC Criteria: June 16, 2017
• First Posted (ACTUAL): June 19, 2017

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2021
• Last Update Submitted That Met QC Criteria: June 9, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Thyroid Diseases
• Other Study ID Numbers: HS#2014-1144; R03DK114642 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No