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

September 28, 2018 updated by: Michael DeBaun, Vanderbilt University

Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease: a Feasibility Trial

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Specific aim 1: To determine acceptability of a clinical trial in which participants are randomly allocated to either a placebo or azithromycin 500 mg 3 days a week for 6 months for adults with SCD who have FEV1<80%.

To assess acceptability of this intervention, investigators will measurement recruitment rate, retention and adherence to the study medication. Recruitment will be assessed by proportion of eligible participants that agree to be randomized. Retention will be measured as proportion randomly allocated who complete the trial. Dropout due to toxicity will be categorized using a questionnaire. Medication adherence will be assessed using the previously validated 8 item modified Morisky medication adherence scale (MMAS-8), where responses are categorized: high adherence (8 points), average adherence (6-7 points), and poor adherence (0-5 points). If recruitment rate is < 60%, the retention rate < 80%, or average adherence rate is ≤5 points, the original protocol will be examined and alternative strategies to enhance recruitment, retention, and adherence will be considered.

Specific aim 2: To evaluate the effect of 6 months of low dose azithromycin therapy on FEV1 and respiratory symptoms in patients with SCA. Baseline FEV1 testing with a portable, in-office spirometer will be completed at study enrollment and at the end of the study period (6 months). The previously validated American Thoracic Society (ATS-DLD-78 for adults) questionnaire will also be used to evaluate respiratory symptoms at baseline and end of the study. Under a separate protocol, investigators will calculate the coefficient of variation for FEV1% predicted in adults with sickle cell disease in order to define the within-subject variability for tests of respiratory function in this specific population, which has not been previously described within the medical literature. Calculation of the coefficient of variation for FEV1 % predicted will be essential for the interpretation of clinically and statistically meaningful changes in spirometry for participants who are treated with azithromycin to improve their baseline pulmonary function when compared to controls.

Study Type

Interventional

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Vanderbilt University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Treatment arm (azithromycin)
Treatment arm: azithromycin 500 mg three times a week for 6 months
Drug: Azithromycin
Study participants will be randomized to the treatment arm (azithromycin 500 mg three times a week for 6 months).
Other Names:
  • Zithromax, zmax, z-pack
Placebo Comparator: Placebo arm
Control arm: placebo three times a week for 6 months
Other: Placebo
Study participants will be randomized to the control arm (placebo three times a week for 6 months).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability of the trial will be assessed by the modified Morisky Medication Adherence Scale (MMAS - 8)
Time Frame: 6 months
Acceptability of the trial will be measured based on three outcomes: recruitment, retention, and adherence rates to therapy. Retention defined as the number of participants that complete the entire study. Recruitment defined as the number of eligible participants that elect to consent to continue with study evaluations. Adherence rate measured based on MMAS score, which was previously validated in children with sickle cell disease (SCD) and scored as follows: high adherence (8 points), average adherence (6 to 7 points) and poor adherence (0 - 5 points).
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in FEV1 % predicted in response to 6 months of low dose azithromycin therapy
Time Frame: 6 months
6 months
Change in respiratory symptom score (by ATS-DLD-78) in response to 6 months of low dose azithromycin therapy
Time Frame: 6 months
6 months
Change in quality of life (by SF-36) in response to 6 months of low dose azithromycin therapy
Time Frame: 6 months
6 months
Number of participants with treatment-related adverse events
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University

Investigators

  • Principal Investigator: Michael R. DeBaun, M.D., M.P.H., Vanderbilt University Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

September 1, 2016

Primary Completion (Anticipated)

October 1, 2018

Study Completion (Anticipated)

October 1, 2018

Study Registration Dates

First Submitted

November 2, 2016

First Submitted That Met QC Criteria

November 7, 2016

First Posted (Estimate)

November 9, 2016

Study Record Updates

Last Update Posted (Actual)

October 2, 2018

Last Update Submitted That Met QC Criteria

September 28, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 161332

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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