Exogenous Allergic Alveolitis, Hypersensitivity Pneumonitis
Conditions
Keywords
Children, Birds, Moulds
Brief summary
Stop exogenous allergic alveolitis (EAA) or hypersensitivity pneumonitis in childhood: healthy into adulthood - a randomized, double-blind, placebo-controlled, parallel-group study to evaluate prednisolone treatment and course of disease. The hypothesis of the study is that the treatment with placebo will not be inferior in terms of Forced Vital Capacity (FVC) improvement than treatment with systemic steroids after 6 months treatment.
Detailed description
After an initial steroid pulse given to all patients, patients will be allocated to the two treatments, i.e., oral prednisolone and Placebo. Experimental intervention: Placebo Control intervention: Prednisolone Duration of intervention per patient: 3 months Follow-up per patient: 3 months Primary Objective: To evaluate outcome of EAA at 6 months and compare the medium term treatment with systemic steroids or placebo. Secondary Objectives: To evaluate the completeness and knowledge of standardized and pedantic allergen elimination in families with a child with EAA. To evaluate the treatment of EAA with systemic steroids compared to placebo at 3 months. To evaluate the safety of the treatment of EAA with outpatient usage of systemic steroids compared to Placebo.
Interventions
DRUGPlacebo
Administer Placebo as anti-inflammatory
DRUGPrednisolone
Administer Prednisolone as anti-inflammatory
Sponsors
Matthias Griese
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
1. Newly or previously diagnosed but not appropriately treated EAA in children, adolescents and young adults, aged between 3 and 25 years. The diagnosis of EAA must be confirmed by independent review of the findings by an expert panel and must be based on the presence of at least 4 of the following findings: * History of appropriate allergen exposure * Restrictive lung function (FVC \< 80% predicted for age and FVC/FEV1 \< 1) testing, if appropriate for age (usually \> 5 y) * Positive serum precipitins for bird/fungus exposed to (other allergens have rarely, if every been demonstrated in children) * Lymphocytosis in BAL (\> 20% of cells are lymphocytes) * HRCT showing the characteristic nodular, linear or reticular opacities, and ground glass pattern with increased attenuation. * Lung biopsy demonstrating lymphocytic alveolitis, bronchiolitis, and non-caseating histiocytic granulomatas. * Controlled allergen exposure followed by characteristic reaction, including fever, coughing, restriction on lung function, hypoxemia/desaturation at rest or with exercise 2. Unchanged inhaled steroids if on; if off, no plans to introduce them in the following 6 months 3. Agreement to home visit by independent study physician
Exclusion criteria
1. Contraindication for usage systemic steroids 2. Critically ill patients needing respiratory support 3. Non-compliance with medical treatments and interventions 4. Women with childbearing potential and not practicing a medically accepted contraception during the trial and a positive pregnancy test (serum or urine) before and at the end of the trial. Reliable contraception are systematic contraceptives (oral, implant, injection) and diaphragm or condoms with spermicide. 5. Pregnancy and lactation. 6. Participation in another trial for EAA during the last 4 weeks or not beyond the time of 4 half-lives of the medication used. In the unlikely event a subject is already in another clinical study but not for EAA, that study must be stopped and the subject may be treated according to this protocol; a latency time between the two studies does not appear reasonable, as acute intervention is necessary for EAA. Treatment may be best done in the frame work of this protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity (FVC). | 6 months | The relative change from baseline through month 6 compared to change from placebo of FVC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Forced Vital Capacity (FVC) | 3 months | FVC measured in accordance to standarized protocol. |
Countries
Germany
Participant flow
Recruitment details
Originally, it was planned to screen 60 subjects to include approximately 40 patients. From January 2015 to July 2016 due to difficulties in funding only 4 children were included in the trial. All met inclusion criteria, were randomized, and completed the trial.
Participants by arm
| Arm | Count |
|---|---|
| Prednisolone 1 Oral prednisolone, anticipated dose:
first month after steroid pulse 0.5 mg/kg bw/d, second month 0.25 mg/kg bw/d, and third month 0.125 mg/kg bw/d in a single morning dose. | 1 |
| Placebo Capsules of placebo will be taken for 3 months. | 1 |
| Prednisolone 2 Oral prednisolone, anticipated dose:
first month after steroid pulse 0.5 mg/kg bw/d, second month 0.25 mg/kg bw/d, and third month 0.125 mg/kg bw/d in a single morning dose. | 1 |
| Prednisolone 3 Oral prednisolone, anticipated dose:
first month after steroid pulse 0.5 mg/kg bw/d, second month 0.25 mg/kg bw/d, and third month 0.125 mg/kg bw/d in a single morning dose. | 1 |
| Total | 4 |
Baseline characteristics
| Characteristic | Prednisolone 3 | Total | Prednisolone 1 | Placebo | Prednisolone 2 |
|---|---|---|---|---|---|
| Age, Customized | 12.9 years | 9.6 years | 8.4 years | 6.6 years | 10.6 years |
| O2 saturation at rest | 97 % | 96.3 % | 90 % | 98 % | 100 % |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 1 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Germany | 1 participants | 4 participants | 1 participants | 1 participants | 1 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 3 |
| other Total, other adverse events | 1 / 1 | 3 / 3 |
| serious Total, serious adverse events | 0 / 1 | 0 / 3 |
Outcome results
Primary
Forced Vital Capacity (FVC).
The relative change from baseline through month 6 compared to change from placebo of FVC.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisolone 1 | Forced Vital Capacity (FVC). | 126 % predicted |
| Placebo | Forced Vital Capacity (FVC). | 103 % predicted |
| Prednisolone 2 | Forced Vital Capacity (FVC). | 84 % predicted |
| Prednisolone 3 | Forced Vital Capacity (FVC). | 65 % predicted |
Secondary
Forced Vital Capacity (FVC)
FVC measured in accordance to standarized protocol.
Time frame: 3 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Prednisolone 1 | Forced Vital Capacity (FVC) | 114 % predicted |
| Placebo | Forced Vital Capacity (FVC) | 95 % predicted |
| Prednisolone 2 | Forced Vital Capacity (FVC) | 85 % predicted |
| Prednisolone 3 | Forced Vital Capacity (FVC) | 76 % predicted |