Overview

This trial is active, not recruiting.

Condition end stage renal disease
Treatments ergocalciferol, placebo
Sponsor Massachusetts General Hospital
Collaborator National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Start date November 2009
End date October 2014
Trial size 181 participants
Trial identifier NCT00892099, 1R01DK084974-01, 2009P-000398

Summary

Infection is the second-leading cause of death in individuals requiring dialysis treatment for kidney failure. New research suggests the high risk of infection may be due in part to low levels of vitamin D, which are extremely common in kidney disease. This study is designed to determine safe and effective ways to raise vitamin D levels while monitoring effects on the immune system.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator, outcomes assessor)
Primary purpose prevention
Arm
(Experimental)
Receives 50,000 IU of ergocalciferol weekly
ergocalciferol vitamin D
50,000 IU tablet given weekly
(Experimental)
Receives 50,000 IU of ergocalciferol per month
ergocalciferol Vitamin D
50,000 IU tablet given monthly
(Placebo Comparator)
Receives no ergocalciferol
placebo
Placebo equivalent of ergocalciferol, given weekly as one tablet

Primary Outcomes

Measure
Serum 25D level
time frame: every 4 weeks for 12 weeks

Secondary Outcomes

Measure
Cytokine profiles
time frame: every 4 weeks for 12 weeks
Serum Calcium
time frame: every 4 weeks for 12 weeks
Serum Phosphate
time frame: every 4 weeks for 12 weeks
Parathyroid Hormone
time frame: Every 4 weeks for 12 weeks
Serum 1,25-dihydroxyvitamin D levels
time frame: every 4 weeks for 12 weeks
Plasma cathelicidin
time frame: every 4 weeks for 12 weeks
All Cause Hospitalizations and Mortality
time frame: 1 year
Infectious Hospitalizations and Mortality
time frame: 1 year
Cardiac Hospitalizations and Mortality
time frame: 1 year

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion criteria - Age ≥ 18 years - Initiating chronic hemodialysis 3x/wk at Massachusetts General Hospital, Brigham and Women's Hospital or Beth Israel Deaconess Medical Center with planned transfer to Massachusetts chronic facility - Serum 25D < 32 ng/ml - Corrected serum calcium < 10.2 mg/dl - Serum phosphate < 5.5 mg/dl - Serum albumin > 3 g/dL - Informed consent Exclusion Criteria - Pregnant or breastfeeding - Women of childbearing potential not practicing one of the following measures of birth control: double-barrier method, hormonal contraceptives for at least 3 months prior to and during study, monogamous relationship with vasectomized partner, total abstinence from sexual intercourse with men during study. - HIV positive - History of allergic reaction to ergocalciferol - Investigator considers subject unsuitable for any reason

Additional Information

Official title DIVINE: Dialysis Infection and Vitamin D In New England
Principal investigator Ravi Thadhani, MD MPH
Description We hypothesize that a profound deficiency of nutritional vitamin D (25-hydroxyvitamin D, 25D) in end-stage renal disease (ESRD) leads to an altered immune response, predisposing to early morbidity and mortality from infection, the second-leading cause of death in ESRD. In addition to impaired renal synthesis of the hormonal form of vitamin D (1,25-dihydroxyvitamin D; 1,25D), ESRD is accompanied by near universal insufficiency of 25D. In-vitro, ex-vivo, and retrospective human studies by our group and others suggest that 25D (and not 1,25D) is intimately linked to immune defense via alterations in the production of inflammatory cytokines and critical antimicrobial peptides including cathelicidin, which we have shown to identify ESRD subjects at risk for infection-related mortality. Ergocalciferol, which is rapidly converted to 25D, is the most widely available form of nutritional vitamin D in the US, yet guidelines to treat ESRD patients with nutritional vitamin D are absent because of limited data supporting its efficacy, safety, and biological effects in this population. To determine effective and safe doses of ergocalciferol in ESRD, we will perform a double blind placebo controlled randomized trial in 120 incident hemodialysis patients (40/arm x 3) with 25D levels < 30ng/ml, comparing two ergocalciferol dosing regimens (50,000 IU/week and 50,000 IU/month) and an identically appearing placebo. The primary outcome will be correction of vitamin D insufficiency (25D >30 ng/ml) at 12 weeks. Serum calcium and phosphate levels will be measured every 4 weeks to assess safety, and blood cytokine and cathelicidin levels will be measured every 4 weeks to determine biological responses. To examine biological effects in greater detail, a subset of subjects from each arm of the study will be further analyzed with serial macrophage gene expression profiles and whole blood cytokine profiles following ex-vivo stimulation with pro-inflammatory mediators (e.g., killed S. aureus). These experiments will inform us on how individuals with ESRD, based on their vitamin D status and the treatment they receive, may respond to infection. Laboratory measures will continue for 12 weeks. Clinical follow-up and monitoring for infection-associated events (including antibiotic use, rates of bacteremia, and sepsis) will continue for 20 weeks. This pilot trial addressing a significant unmet need in nephrology will involve basic, translational, and clinical investigators experienced in vitamin D research, infection and inflammation, and in trials involving ESRD subjects. These data will provide an important foundation for designing future clinical trials rigorously assessing the effect of nutritional vitamin D on infectious and other outcomes in ESRD.
Trial information was received from ClinicalTrials.gov and was last updated in June 2014.
Information provided to ClinicalTrials.gov by Massachusetts General Hospital.