Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC Study) (DISC)

• ClinicalTrials.gov Identifier: NCT01426256
• Recruitment Status: Completed
• First Posted: August 31, 2011
• Last Update Posted: July 13, 2017
• Sponsor: Emory University
• Collaborator: Cystic Fibrosis Foundation
• Information provided by (Responsible Party): Vin Tangpricha, MD, PH.D, Emory University

Tracking Information

• First Submitted Date: August 29, 2011
• First Posted Date: August 31, 2011
• Last Update Posted Date: July 13, 2017
• Study Start Date: October 2011
• Actual Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: November 16, 2016): Study enrollment to next pulmonary exacerbation requiring any antibiotics, hospitalization or death. [ Time Frame: 12 months ]
• Original Primary Outcome Measures (submitted: August 30, 2011): The composite measure of deaths and re-hospitalizations after randomization [ Time Frame: 12 months ]

Current Secondary Outcome Measures (submitted: November 16, 2016)

• inflammation [ Time Frame: 12 months ]
  We will examine whether the high-dose vitamin D treatment regimen decreases the pro-inflammatory cytokines, IL-6, IL-8, and TNF- α.
• mortality as a separate outcome [ Time Frame: 12 months ]
• re-hospitalization as a separate outcome [ Time Frame: 12 months ]
• anti-microbial proteins [ Time Frame: 12 months ]
  We will examine whether the high-dose vitamin D treatment regimen increases cathelicidin and hBD-2 mRNA expression in both peripheral blood mononuclear cells (PBMCs) and induced sputum (by quantitative PCR).
• Lung function [ Time Frame: 12 months ]
  We will examine whether high dose vitamin D improves serial lung function, as measured by FEV1
• Antibiotic use [ Time Frame: 12 months ]
  Rates of pulmonary exacerbation requiring antibiotics due to presumed infection after 12 month
• glucose metabolism [ Time Frame: 12 months ]
  Rates of new onset diabetes and mean glucose values in each group

Original Secondary Outcome Measures (submitted: August 30, 2011)

• inflammation [ Time Frame: 12 months ]
  We will examine whether the high-dose vitamin D treatment regimen decreases the pro-inflammatory cytokines, IL-6, IL-8, and TNF- α.
• mortality as a separate outcome [ Time Frame: 12 months ]
• re-hospitalization as a separate outcome [ Time Frame: 12 months ]
• anti-microbial proteins [ Time Frame: 12 months ]
  We will examine whether the high-dose vitamin D treatment regimen increases cathelicidin and hBD-2 mRNA expression in both peripheral blood mononuclear cells (PBMCs) and induced sputum (by quantitative PCR).
• Lung function [ Time Frame: 12 months ]
  We will examine whether high dose vitamin D improves serial lung function, as measured by FEV1
• Antibiotic use [ Time Frame: 12 months ]
  Rates of pulmonary exacerbation requiring antibiotics due to presumed infection after 12 month

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Vitamin D for Enhancing the Immune System in Cystic Fibrosis (DISC Study)
• Official Title: Vitamin D for Enhancing the Immune System in Cystic Fibrosis
• Brief Summary: The purpose of this study is determine if high-dose vitamin D supplementation improves clinical outcomes related to lung function and immunity in patients with Cystic Fibrosis who are admitted to the hospital with an acute lung infection.
• Detailed Description: Patients with Cystic Fibrosis (CF) have a shorter life span than the general population due to complications with lung infections, which eventually progress to lung failure. New research has suggested that high levels of vitamin D may be protective against lung infections and may promote the action of anti-bacterial proteins needed to ward off infections. Research has also suggested that high vitamin D levels are linked to lower mortality rates; however these hypotheses have not been adequately studied in patients with CF. An investigation of the effects of vitamin D supplementation is of particular interest in this population because patients with CF generally have high rates of vitamin D deficiency. The investigators have preliminary data from a previous study suggesting that vitamin D supplementation in patients with CF lowers markers of inflammation, promotes anti-bacterial proteins, and reduces mortality. In this proposed multi-center study the investigators will examine the effects of a high dose vitamin D supplementation on patients with CF who are admitted to the hospital for lung infection. The investigators will use a randomized, placebo-controlled trial design to determine if mortality and infection rates over 1 year are reduced in patients who receive the high-dose vitamin D supplementation compared to those who receive placebo. The investigators will also determine if vitamin D affects markers of inflammation and anti-bacterial proteins, as well as CF-related clinical outcomes, such as lung function. The investigators plan to recruit 280 adults and adolescents with CF (ages > 16yrs), with approximately 150 subjects recruited at Emory (Emory University Hospital and Children's Healthcare of Atlanta). Participants will initially be seen by the study researchers during the first week of in-patient hospitalization, and they will be followed over the course of one year during their regularly-scheduled out-patient CF clinic visits. The treatment group will receive an initial oral bolus dose of 250,000 IU vitamin D, and at 3 months follow-up they will receive 50,000 IU vitamin D every other week. Current CF Guidelines for vitamin D supplementation recommend a daily intake of 800 IU of vitamin D per day, therefore in addition to the vitamin D or placebo they receive at the beginning of the study and at 3 months, all participants will receive 800 IU of vitamin D daily. If our hypotheses are correct, this study has potential for reducing infection and promoting survival in patients with CF using vitamin D, a relatively inexpensive supplement.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Cystic Fibrosis
• Respiratory Tract Infections

Intervention

Dietary Supplement: Cholecalciferol

Bolus dose of 250,000 IU during hospitalization + maintenance dose of 50,000 IU vitamin D every other week to be initiated 3 months after bolus dose

Other Name: Vitamin D

Study Arms

• Experimental: Cholecalciferol (Vitamin D3)
  Patients will be given 250,000 IU cholecalciferol in one bolus oral dose while they are in the hospital. Three months after the initial bolus dose, patients will take 50,000 IU oral cholecalciferol every other week for 9 months.
  Intervention: Dietary Supplement: Cholecalciferol
• No Intervention: Placebo
  Patients will be given placebo pills in one bolus oral dose while they are in the hospital. Three months after the initial bolus dose, patients will take a placebo pill every other week for 9 months.

Publications *

• Wolfenden LL, Judd SE, Shah R, Sanyal R, Ziegler TR, Tangpricha V. Vitamin D and bone health in adults with cystic fibrosis. Clin Endocrinol (Oxf). 2008 Sep;69(3):374-81. doi: 10.1111/j.1365-2265.2008.03216.x. Epub 2008 Feb 11.
• Khazai NB, Judd SE, Jeng L, Wolfenden LL, Stecenko A, Ziegler TR, Tangpricha V. Treatment and prevention of vitamin D insufficiency in cystic fibrosis patients: comparative efficacy of ergocalciferol, cholecalciferol, and UV light. J Clin Endocrinol Metab. 2009 Jun;94(6):2037-43. doi: 10.1210/jc.2008-2012. Epub 2009 Mar 31.
• Pepper KJ, Judd SE, Nanes MS, Tangpricha V. Evaluation of vitamin D repletion regimens to correct vitamin D status in adults. Endocr Pract. 2009 Mar;15(2):95-103. doi: 10.4158/EP.15.2.95.
• Tangpricha V, Lukemire J, Chen Y, Binongo JNG, Judd SE, Michalski ES, Lee MJ, Walker S, Ziegler TR, Tirouvanziam R, Zughaier SM, Chesdachai S, Hermes WA, Chmiel JF, Grossmann RE, Gaggar A, Joseph PM, Alvarez JA. Vitamin D for the Immune System in Cystic Fibrosis (DISC): a double-blind, multicenter, randomized, placebo-controlled clinical trial. Am J Clin Nutr. 2019 Mar 1;109(3):544-553. doi: 10.1093/ajcn/nqy291. Erratum In: Am J Clin Nutr. 2023 May;117(5):1048.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 11, 2017): 91
• Original Estimated Enrollment (submitted: August 30, 2011): 280
• Actual Study Completion Date: July 2017
• Actual Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Adult and adolescent CF patients
• age >16 years
• admitted to the inpatient hospital setting for a pulmonary exacerbation of cystic fibrosis
• enrolled within 72 hours of admission
• able to tolerate oral medications
• expected to survive hospitalization

Exclusion Criteria:

• Inability to obtain or declined informed consent from the subject and/or legally authorized representative
• History of serum 25(OH)D >55 ng/mL in the past 12 months
• History of serum 25(OH)D <10 ng/mL in the past 12 months
• Current intake of more than 2,000 IU of vitamin D
• intake of 2,000 IU of vitamin D or its equivalent weekly dose (14,000 IU) for more than 1 week at any time within the past 60 days or intake of greater than vitamin D 10,000 IU once at anytime in the past 60 days
• Pregnancy or plans to become pregnant during the course of the study (12 months)
• History of disorders associated with hypercalcemia including parathyroid disease
• Current hypercalcemia (albumin-corrected serum calcium >10.8 mg/dL or ionized calcium >5.2 mg/dL)
• History of nephrolithiasis
• Chronic kidney disease worse than stage III (<60 ml/min)
• Oral or intravenous glucocorticoid use currently or in the past month
• History of lung transplantation or awaiting lung transplant
• patient in hospice care
• FEV1% predicted <20%
• Current significant hepatic dysfunction total bilirubin > 2.5 mg/dL with direct bilirubin > 1.0 mg/dL
• Current use of cytotoxic or immunosuppressive drugs
• History of AIDS
• History of illicit drug abuse (defined as history of enrollment into a drug rehabilitation program or hospital visits due to drug use within the past 3 years or any use of the following drugs in the past 6 months (cocaine, opiates, amphetamines, marijuana) or any positive toxicology screen for (cocaine, opiates, amphetamines, marijuana)
• Previous enrollment in the study
• Current enrollment in another intervention trial
• Too ill to participate in study based on investigator's or study team's opinion

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 16 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01426256
• Other Study ID Numbers: IRB00052829; TANGOR11A0 ( Other Identifier: Other )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Vin Tangpricha, MD, PH.D, Emory University
• Original Responsible Party: Emory University
• Current Study Sponsor: Emory University
• Original Study Sponsor: Same as current
• Collaborators: Cystic Fibrosis Foundation

Investigators

• Principal Investigator: Vin Tangpricha, MD, PhD; Emory University

• PRS Account: Emory University
• Verification Date: July 2017