DIVINE: Dialysis Infection and Vitamin D In New England

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Ravi Thadhani, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00892099
First received: April 30, 2009
Last updated: September 3, 2013
Last verified: September 2013
  Purpose

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.


Condition Intervention
End Stage Renal Disease
Drug: Ergocalciferol
Other: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: DIVINE: Dialysis Infection and Vitamin D In New England

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Serum 25D level [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Cytokine profiles [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: No ]
  • Serum Calcium [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: Yes ]
  • Serum Phosphate [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: Yes ]
  • Parathyroid Hormone [ Time Frame: Every 4 weeks for 12 weeks ] [ Designated as safety issue: Yes ]
  • Serum 1,25-dihydroxyvitamin D levels [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: No ]
  • Plasma cathelicidin [ Time Frame: every 4 weeks for 12 weeks ] [ Designated as safety issue: No ]
  • All Cause Hospitalizations and Mortality [ Time Frame: Study duration ] [ Designated as safety issue: Yes ]
  • Infectious Hospitalizations and Mortality [ Time Frame: study duration ] [ Designated as safety issue: Yes ]
  • Cardiac Hospitalizations and Mortality [ Time Frame: study duration ] [ Designated as safety issue: Yes ]

Enrollment: 181
Study Start Date: November 2009
Estimated Study Completion Date: November 2013
Estimated Primary Completion Date: November 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High Dose Ergocalciferol
Receives 50,000 IU of ergocalciferol weekly
Drug: Ergocalciferol
50,000 IU tablet given weekly
Other Name: vitamin D
Experimental: Low Dose Ergocalciferol
Receives 50,000 IU of ergocalciferol per month
Drug: Ergocalciferol
50,000 IU tablet given monthly
Other Name: Vitamin D
Placebo Comparator: Placebo
Receives no ergocalciferol
Other: Placebo
Placebo equivalent of ergocalciferol, given weekly as one tablet

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00892099

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Ravi Thadhani, MD MPH Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Ravi Thadhani, Director of Clinical Research in Nephrology, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00892099     History of Changes
Other Study ID Numbers: 2009P-000398, 1R01DK084974-01
Study First Received: April 30, 2009
Last Updated: September 3, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
end stage renal disease
hemodialysis

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Ergocalciferols
Vitamin D
Vitamins
Bone Density Conservation Agents
Physiological Effects of Drugs
Pharmacologic Actions
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on April 22, 2014