PRETELL: PREvention of TELomere-related Complications After Lung Transplant

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of Danzol in lung transplant recipients with short telomeres. Subjects with short telomeres recipient of lung transplant, will be randomized in the first month post-transplant to either placebo or Danazol (200mg bid) in a 2:1 ratio.

Official Title
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PRETELL: PREvention of TELomere-related Complications After Lung Transplant

Conditions
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Short Telomere Length, Lung Transplant

Intervention / Treatment
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* Drug: Danazol Pill
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age greater than 18 Ability to give informed consent Recipient of lung transplantation Short telomeres assessed either pre-transplant or post-transplant with FLOW-FISH as lymphocyte telomere length <10th percentile predicted for age Clinically stable one month after lung transplant Exclusion Criteria: Patients on androgen hormones to include testosterone or high dose estrogen (estradiol 0.5 mg/day or greater) during 12 months prior to enrollment Patients with active thrombosis or thromboembolic disease and history of such events unless thrombosis is line related. Undiagnosed abnormal genital bleeding, porphyria, androgen-dependent tumor, or prostatic hypertrophy Patients with active hepatitis B or C Patients who have received a bone marrow transplant Clinically unstable after lung transplantation Current pregnancy, or unwillingness to take be on two forms of contraceptives including a barrier method of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during the course of the study Lactating women, due to the potentially harmful effects on the nursing child Patients with abnormal liver function AST, ALT >3 times normal Subjects with a history of benign intracranial hypertension Subjects with a history of liver disease not limited to alcoholic hepatitis/cirrhosis, non-alcoholic steatohepatitis (NASH), autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and/or history of hepatic adenoma. Subjects with poorly controlled or uncontrolled Type I or II diabetes mellitus Significant renal abnormalities GFR< 40 ml/min/m2 Significant cardiac dysfunction with ejection fraction less than 50% Moribund status such as death is expected in the coming year Currently taking carbamazepine, pimozide or lomitapide Inability to understand the investigational nature of the study or to give informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double blind 2:1 ratio
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo comparison | Drug: Placebo<br>* Placebo twice a day<br>|
| Active Comparator: Danazol Pill<br>Danazol 200mg orally twice a day | Drug: Danazol Pill<br>* Danazol 200 mg orally twice a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | The incidence, severity, outcome, and relationship to study treatment of adverse events and serious adverse events. Change from baseline in clinical laboratory test results. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of WBC <2000/µl | -Occurrence of WBC <2000/µl at any time during study period. | 48 weeks | 
| Cumulative number of events where WBC < 2000/µl | - Evaluating cumulative number of events where WBC < 2000/µl | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Danazol, Prevention, Leukopenia, Short telomere, Lung transplant