Back to results

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

Primary Purpose

Cystic Fibrosis, Allergic Bronchopulmonary Aspergillosis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

cholecalciferol (Vitamin D3)

About this trial

This is an interventional treatment trial for Cystic Fibrosis focused on measuring cystic fibrosis, Allergic bronchopulmonary aspergillosis, A. fumigatus, Immune response

Eligibility Criteria

12 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female ≥ 12 years of age at enrollment
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
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.
Clinically stable at enrollment as assessed by the site investigator
Past or present respiratory culture positive for Aspergillus fumigatus
IgE ≥ 250 and/or presence of class II or higher aspergillus specific IgE on enrollment
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

Sites / Locations

Comprehensive Lung Center - Falk Clinic
Children's Hospital of Pittsburgh of UPMC

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Open label

Arm Description

open label Vitamin D

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

Full Information

NCT ID

NCT01222273

First Posted

October 14, 2010

Last Updated

March 2, 2018

Sponsor

University of Pittsburgh

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT01222273

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2018

Overall Recruitment Status

Completed

Study Start Date

September 2010 (undefined)

Primary Completion Date

September 2013 (Actual)

Study Completion Date

September 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Pittsburgh

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cystic Fibrosis, Allergic Bronchopulmonary Aspergillosis

Keywords

cystic fibrosis, Allergic bronchopulmonary aspergillosis, A. fumigatus, Immune response

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Open label

Arm Type

Other

Arm Description

open label Vitamin D

Intervention Type

Dietary Supplement

Intervention Name(s)

cholecalciferol (Vitamin D3)

Other Intervention Name(s)

cholecalciferol

Intervention Description

4,000 IU of cholecalciferol (Vitamin D3) orally every day for six months

Primary Outcome Measure Information:

Title

Number of Participants With Aspergillus Induced IL-13 Responses in CD4+ T-cells

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Change in Patient Total IgE Levels

Description

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

Time Frame

6 months

Title

Change in Patient Aspergillus Specific IgE Levels

Description

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

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

12 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female ≥ 12 years of age at enrollment Confirmed diagnosis of CF based on the following criteria: One or more clinical features consistent with the CF phenotype AND (b or c) Positive sweat chloride > 60 mEq/liter (by pilocarpine iontophoresis) two identifiable mutations consistent with CF 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. Clinically stable at enrollment as assessed by the site investigator Past or present respiratory culture positive for Aspergillus fumigatus IgE ≥ 250 and/or presence of class II or higher aspergillus specific IgE on enrollment 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joseph M Pilewski, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Jay K Kolls, MD

Organizational Affiliation

University of Pittsburgh

Official's Role

Study Director

Facility Information:

Facility Name

Comprehensive Lung Center - Falk Clinic

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15213

Country

United States

Facility Name

Children's Hospital of Pittsburgh of UPMC

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

27011794

Citation

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.

Results Reference

derived

Links:

URL

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4801182/

Description

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

Learn more about this trial

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

We'll reach out to this number within 24 hrs