End Stage Renal DiseaseNCT00892099
DIVINE: Dialysis Infection and Vitamin D In New England
A study testing Ergocalciferol in people with End Stage Renal Disease, run by Massachusetts General Hospital at 3 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Renal Disease
- What is being tested?
- Ergocalciferol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 105 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2009to Oct 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02115
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
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.
Read the 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.
- Conditions
- End Stage Renal Disease
- Being tested
- Ergocalciferol, Placebo
- Keywords
- end stage renal disease, hemodialysis
- Medical subject headings
- Kidney Failure, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ErgocalciferolDrug
Also called vitamin D
50,000 IU tablet given weekly
ErgocalciferolDrug
Also called Vitamin D
50,000 IU tablet given monthly
PlaceboOther
Placebo equivalent of ergocalciferol, given weekly as one tablet
| Study group | Role | What they receive |
|---|---|---|
| High Dose Ergocalciferol | Experimental | Receives 50,000 IU of ergocalciferol weekly Receives: Drug: Ergocalciferol |
| Low Dose Ergocalciferol | Experimental | Receives 50,000 IU of ergocalciferol per month Receives: Drug: Ergocalciferol |
| Placebo | Placebo comparator | Receives no ergocalciferol Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum 25D Level
Measured: 12 weeks
Secondary outcomes (5)
Serum Calcium
serum calcium levels (mg/dL)
Measured: every 4 weeks for 12 weeks
Serum Phosphate
serum phosphate levels (mmol/L)
Measured: every 4 weeks for 12 weeks
Serum 25-OH Vitamin D
serum 25-OH vitamin D levels (ng/mL)
Measured: every 4 weeks for 12 weeks
Serum 1,25(OH)2 Levels
serum 1,25(OH) vitamin D levels (pg/mL)
Measured: At week 12
Parathyroid Hormone
serum PTH levels (pg/mL)
Measured: every 4 weeks for 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2009 (estimated)
- Study startNov 2009
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 105 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ravi Thadhani, Massachusetts General Hospital
- Investigators
- Ravi Thadhani, MD MPH, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00892099
- Sponsor's protocol ID
- 2009P-000398
- Other IDs
- R01DK084974
- Status last verified
- Mar 2018
- First submitted
- 30 Apr 2009
- Last updated
- 20 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bhan I, Camargo CA Jr, Wenger J, Ricciardi C, Ye J, Borregaard N, Thadhani R. Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. J Allergy Clin Immunol. 2011 May;127(5):1302-4.e1. doi: 10.1016/j.jaci.2010.12.1097. Epub 2011 Feb 9. No abstract available.
PubMed 21310475Ishir Bhan, Dorothy A Dobens, Caitlin A. Trottier, Julia Beth Wenger, Hector Tamez, Joseph James Deferio, Kathryn J. Lucchesi, Ravi I. Thadhani. The DIVINE Trial: Dialysis Infection and Vitamin D in New England J. Am. Soc. Nephrol 24:2013 (Abstract: SA-PO1082)
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- DIVINE: Dialysis Infection and Vitamin D In New England
- ClinicalTrials.gov ID
- NCT00892099
- Acronym / sponsor ID
- 2009P-000398
- Conditions
- End Stage Renal Disease
- Keywords
- end stage renal disease, hemodialysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 105 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Nov 2009
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 4 May 2009 (estimated)
- Results
- Posted 8 Jun 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| High Dose Ergocalciferol | Experimental | Drug: ErgocalciferolReceives 50,000 IU of ergocalciferol weekly |
| Low Dose Ergocalciferol | Experimental | Drug: ErgocalciferolReceives 50,000 IU of ergocalciferol per month |
| Placebo | Placebo comparator | Other: PlaceboReceives no ergocalciferol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ErgocalciferolAlso: vitamin D50,000 IU tablet given weekly | Drug | High Dose Ergocalciferol |
| ErgocalciferolAlso: Vitamin D50,000 IU tablet given monthly | Drug | Low Dose Ergocalciferol |
| PlaceboPlacebo equivalent of ergocalciferol, given weekly as one tablet | Other | Placebo |
Primary outcome
Serum 25D Level
Time frame: 12 weeks
5 secondary outcomes
Serum Calcium
Time frame: every 4 weeks for 12 weeks
Serum Phosphate
Time frame: every 4 weeks for 12 weeks
Serum 25-OH Vitamin D
Time frame: every 4 weeks for 12 weeks
Serum 1,25(OH)2 Levels
Time frame: At week 12
Parathyroid Hormone
Time frame: every 4 weeks for 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21310475Bhan I, Camargo CA Jr, Wenger J, Ricciardi C, Ye J, Borregaard N, Thadhani R. Circulating levels of 25-hydroxyvitamin D and human cathelicidin in healthy adults. J Allergy Clin Immunol. 2011 May;127(5):1302-4.e1. doi: 10.1016/j.jaci.2010.12.1097. Epub 2011 Feb 9. No abstract available.
- Results publicationIshir Bhan, Dorothy A Dobens, Caitlin A. Trottier, Julia Beth Wenger, Hector Tamez, Joseph James Deferio, Kathryn J. Lucchesi, Ravi I. Thadhani. The DIVINE Trial: Dialysis Infection and Vitamin D in New England J. Am. Soc. Nephrol 24:2013 (Abstract: SA-PO1082)
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ravi Thadhani, MD MPH principal investigator
Massachusetts General Hospital
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ergocalciferol in people with End Stage Renal Disease, run by Massachusetts General Hospital at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jun 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum 25D Level (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00892099, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Apr 2018.