Open-label Vitamin D Trial for Patients With Cystic Fibrosis and Allergic Bronchopulmonary Aspergillosis

The purpose of this study is to see if giving people with CF and ABPA enough vitamin D to make their blood levels of the vitamin higher, will reduce the allergic response in their body and make the symptoms caused by ABPA better.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Allergic Bronchopulmonary Aspergillosis
• Intervention / Treatment: Dietary supplement: cholecalciferol (Vitamin D3)

Detailed Description

Many patients with cystic fibrosis (CF) cough up mucus or have throat cultures that grow a common fungus called Aspergillus. In patients with CF, aspergillus is not known to cause direct damage to the lungs, but some patients respond with an allergic reaction that causes them to wheeze, cough, or have difficulty breathing. This allergic reaction is called ABPA. Current treatment for ABPA includes high dose steroids and an "anti-fungal" medicine. Treatment with steroids may be problematic for some people due to its side effects on blood sugar levels and the bones. Steroids are medications that decrease inflammation, including prednisone, medrol, dexamethasone and others.

Ongoing research at UPMC on the study "Mechanisms of Immune Tolerance in ABPA" has studied people with CF and ABPA versus those patients with CF that just grow A. fumigatus (Af) in the sputum, but do not have ABPA. You may have participated in this study. This study has shown that people with CF with the fungus, Af, in their sputum but who do not have ABPA have more of a certain type of cell in their blood that helps the body to regulate or suppress allergic reactions than those people with CF and ABPA.

Recent studies have demonstrated that Vitamin D is a critical factor in the development of these cells that suppress allergic reactions. People with CF, due to their pancreatic insufficiency that causes them to have difficulty absorbing fat, also have lower levels of the fat soluble vitamins which include vitamin D. In the study done at UPMC, "Mechanisms of Immune Tolerance in ABPA", people with CF and ABPA had significantly lower vitamin D levels than people with CF who did not have ABPA.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
    • Pittsburgh, Pennsylvania, United States, 15213
      • Comprehensive Lung Center - Falk Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female ≥ 12 years of age at enrollment

2. Confirmed diagnosis of CF based on the following criteria:

   1. One or more clinical features consistent with the CF phenotype AND (b or c)
   2. Positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis)
   3. two identifiable mutations consistent with CF
3. Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.
4. Clinically stable at enrollment as assessed by the site investigator
5. Past or present respiratory culture positive for Aspergillus fumigatus
6. IgE ≥ 250 and/or presence of class II or higher aspergillus specific IgE on enrollment
7. Ability to comply with medication use, study visits and study procedures as judged by the site investigator -

Exclusion Criteria:

• 1. Systemic corticosteroids (1 mg/kg if < 20 kg or > 20 mg of prednisone per day),.

  2. Investigational drug use within 30 days of screening 3. Laboratory abnormalities at screening

  a. Serum Calcium > 11 mg/dl b. 25(OH) D > 50 ng/ml at screening. c. Creatinine ≥ 1.5, or estimated GFR <60 by Cockcroft-Gault or MDRD equation. d. LFT≥ 3xULN

  4. History of transplantation or currently on lung transplant list 5. Positive serum pregnancy test at screening (to be performed on all post-menarche females) 6. Pregnant, breastfeeding, or if post-menarche female, unwilling to practice birth control during participation in the study 7. Presence of a condition or abnormality that in the opinion of the site investigator would compromise the safety of the subject or the quality of the data 8. Diagnosis of HIV and a CD4+ T cell count below 500 cells/ml or active hepatitis B or C infection.

  9. Undergoing therapy for non-tuberculous mycobacterial infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Open label; open label Vitamin D	Dietary supplement: cholecalciferol (Vitamin D3); 4,000 IU of cholecalciferol (Vitamin D3) orally every day for six months; Other Names: cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Aspergillus Induced IL-13 Responses in CD4+ T-cells	To test the hypothesis that supplementation with Vitamin D in CF patients with ABPA will reduce Aspergillus induced IL-13 responses in peripheral CD4+ T-cells. Response confirmed for each individual patient and recorded as number of participants with response.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Patient Total IgE Levels	To test the hypothesis that supplementation with Vitamin D in CF patients with ABPA will reduce total IgE levels by the end of the 24-week period	6 months
Change in Patient Aspergillus Specific IgE Levels	To test the hypothesis that supplementation with Vitamin D in CF patients with ABPA will reduce aspergillus specific IgE levels by the end of the 24-week period	6 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Joseph M Pilewski, MD, University of Pittsburgh; Study Director: Jay K Kolls, MD, University of Pittsburgh

Publications and helpful links

General Publications

• Nguyen NL, Pilewski JM, Celedon JC, Mandalapu S, Blanchard ML, DeRicco A, Hartigan E, Alcorn JF, Kolls JK. Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: a phase one open-label study. Asthma Res Pract. 2015;1:3. doi: 10.1186/s40733-015-0003-5. Epub 2015 Jun 4.

Helpful Links

• Vitamin D supplementation decreases Aspergillus fumigatus specific Th2 responses in CF patients with aspergillus sensitization: a phase one open-label study

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: October 14, 2010
• First Submitted That Met QC Criteria: October 14, 2010
• First Posted (Estimate): October 18, 2010

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 2, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: cystic fibrosis; Immune response; Allergic bronchopulmonary aspergillosis; A. fumigatus
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Bacterial Infections and Mycoses; Respiratory Hypersensitivity; Hypersensitivity; Mycoses; Pancreatic Diseases; Lung Diseases, Fungal; Fibrosis; Cystic Fibrosis; Aspergillosis; Pulmonary Aspergillosis; Aspergillosis, Allergic Bronchopulmonary; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: PRO09090370; 7P50HL084932-04 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

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