Cystic Fibrosis, Allergic Bronchopulmonary Aspergillosis
Conditions
Keywords
cystic fibrosis, Allergic bronchopulmonary aspergillosis, A. fumigatus, Immune response
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.
Interventions
DIETARY_SUPPLEMENTcholecalciferol (Vitamin D3)
4,000 IU of cholecalciferol (Vitamin D3) orally every day for six months
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Aspergillus Induced IL-13 Responses in CD4+ T-cells | 6 months | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient Total IgE Levels | 6 months | 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 | 6 months | 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 |
Countries
United States
Participant flow
Recruitment details
The CF Foundation patient registry will be queried for patients meeting inclusion/exclusion criteria. A recruitment letter will be sent to these patients. Additionally, patients/parents of patients will be approached regarding study participation by the investigator at routine clinic visits.
Participants by arm
| Arm | Count |
|---|---|
| Cholecalciferol 2000 Units of cholecalciferol once daily
cholecalciferol (Vitamin D3): 4,000 IU of cholecalciferol (Vitamin D3) orally every day for six months | 7 |
| Total | 7 |
Baseline characteristics
| Characteristic | Cholecalciferol | — |
|---|---|---|
| Age, Categorical <=18 years | 2 Participants | — |
| Age, Categorical >=65 years | 0 Participants | — |
| Age, Categorical Between 18 and 65 years | 5 Participants | — |
| Age, Continuous | 21.91 years STANDARD_DEVIATION 2.69 | — |
| Asp IgE | 18.4 kUA/I STANDARD_DEVIATION 14.7 | — |
| BMI | 22.5 kg/m^2 STANDARD_DEVIATION 10.68 | — |
| Genotype MEG/G542X | 1 Participants | — |
| Genotype neg/ΔF508 | 1 Participants | — |
| Genotype ΔF508/1213delT | 1 Participants | — |
| Genotype ΔF508/612+ 1G-T | 1 Participants | — |
| Genotype ΔF508/R1162X | 1 Participants | — |
| Genotype ΔF508/R553X | 1 Participants | — |
| Genotype ΔF508/ΔF508 | 1 Participants | — |
| IgE | 344.6 IU/mL STANDARD_DEVIATION 284.9 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 7 participants | — |
| Sex: Female, Male Female | 4 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 7 |
| serious Total, serious adverse events | 0 / 7 |
Outcome results
Primary
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.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cholecalciferol | Number of Participants With Aspergillus Induced IL-13 Responses in CD4+ T-cells | 7 Participants |
Secondary
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
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Change in Patient Aspergillus Specific IgE Levels | 11.73 kUA/I | Standard Deviation 3.581 |
Secondary
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
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cholecalciferol | Change in Patient Total IgE Levels | 312.6 IU/mL | Standard Deviation 77.66 |