Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease

• Status: Withdrawn
• Trial end date: 2018-10-01
• Target enrollment: 0
• Participant gender: All

Summary

Sickle cell anemia (SCA) is a life-threatening, monogenic disorder associated with early death when compared to individuals without SCA. Pulmonary complications, namely acute chest syndrome, obstructive lung disease and pulmonary hypertension, are the most common causes of death in patients with SCA. Recent studies suggest that lung specific inflammation is a hallmark of SCA and underlies pulmonary pathology. To date, no therapy has been shown to improve the pulmonary complications of SCA. Macrolides have pleomorphic effects in the lung with improvement in pulmonary function, symptoms and inflammatory markers demonstrated in several inflammatory pulmonary conditions such as cystic fibrosis, asthma, COPD and post-transplant bronchiolitis obliterans. Investigators hypothesize that low dose macrolide therapy is well tolerated and can improve pulmonary function and symptoms in patients with SCA. The objective of this project is to assess the feasibility of macrolides to attenuate or reverse the decrease in %predicted FEV1 in adults with SCA in a single-site, randomized, placebo-controlled feasibility trial.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Vanderbilt University
• Treatments: Azithromycin

Criteria

Inclusion criteria:

1. Established diagnosis of sickle cell disease (HbSS, HbSC, HbS/β+, HbS/β0)

2. Age between 18-50 years

3. FEV1 < 80% predicted

4. Willingness to make return visits and availability by telephone for the duration of the study.

Exclusion criteria:

1. Acute respiratory symptoms

2. FEV1>80%

3. Inability to swallow pills

4. Hypersensitivity to macrolides.

5. History of cardiac arrhythmias

6. Prolonged QTc interval (>500 ms) at on baseline EKG

7. Baseline impairment of hearing by pure tone audiometry defined as patients with age-adjusted hearing thresholds >95th percentile at any one frequency of 500, 1000, 2000 and 4000 Hz.

8. The presence of a diagnosis other than SCD that results in the patient being medically unstable, or having a predicted life expectancy less than 1 year.

9. Special patient groups: prisoners, pregnant women, institutionalized patients

10. Women who are at risk of becoming pregnant during the study, and who refuse to use an acceptable means of birth control (hormonal based oral, intrauterine device or barrier contraception) for the duration of the study.

11. Patients taking tacrolimus, pimozide, disopyramide, cyclosporine, nelfinavir, bromocriptine, or hexobarbital.

12. Patients taking any medications that prolong QTc interval.