Lung Transplant, Short Telomere Length
Conditions
Keywords
Danazol, Short telomere, Lung transplant, Prevention, Leukopenia
Brief summary
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.
Interventions
DRUGDanazol Pill
Danazol 200 mg orally twice a day
DRUGPlacebo
Placebo twice a day
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Similar tablets will be generated.
Intervention model description
Randomized double blind 2:1 ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age greater than 18 2. Ability to give informed consent 3. Recipient of lung transplantation 4. Short telomeres assessed either pre-transplant or post-transplant with FLOW-FISH as lymphocyte telomere length \<10th percentile predicted for age 5. Clinically stable one month after lung transplant
Exclusion criteria
1. Patients on androgen hormones to include testosterone or high dose estrogen (estradiol 0.5 mg/day or greater) during 12 months prior to enrollment 2. Patients with active thrombosis or thromboembolic disease and history of such events unless thrombosis is line related. 3. Undiagnosed abnormal genital bleeding, porphyria, androgen-dependent tumor, or prostatic hypertrophy 4. Patients with active hepatitis B or C 5. Patients who have received a bone marrow transplant 6. Clinically unstable after lung transplantation 7. 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 8. Lactating women, due to the potentially harmful effects on the nursing child 9. Patients with abnormal liver function AST, ALT \>3 times normal 10. Subjects with a history of benign intracranial hypertension 11. 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. 12. Subjects with poorly controlled or uncontrolled Type I or II diabetes mellitus 13. Significant renal abnormalities GFR\< 40 ml/min/m2 14. Significant cardiac dysfunction with ejection fraction less than 50% 15. Moribund status such as death is expected in the coming year 16. Currently taking carbamazepine, pimozide or lomitapide 17. Inability to understand the investigational nature of the study or to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | 48 weeks | The incidence, severity, outcome, and relationship to study treatment of adverse events and serious adverse events. Change from baseline in clinical laboratory test results. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of WBC <2000/µl | 48 weeks | -Occurrence of WBC \<2000/µl at any time during study period. |
| Cumulative number of events where WBC < 2000/µl | 48 weeks | \- Evaluating cumulative number of events where WBC \< 2000/µl |
Other
| Measure | Time frame | Description |
|---|---|---|
| Telomere length | 48 weeks | -Measure change in lymphocyte telomere length at end of study drug administration compared to screening |
Outcome results
None listed