Clinical trial NCT04807309: PRETELL: PREvention of TELomere-related Complications After Lung Transplant
Official title: PRETELL: PREvention of TELomere-related Complications After Lung Transplant
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Short Telomere Length
Lung Transplant
Keywords: Danazol
Short telomere
Lung transplant
Prevention
Leukopenia
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
First posted: 2021-03-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double blind 2:1 ratio
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 48 weeks
Secondary outcomes:
measure: Occurrence of WBC <2000/µl
timeFrame: 48 weeks
measure: Cumulative number of events where WBC < 2000/µl
timeFrame: 48 weeks
Other outcomes:
measure: Telomere length
timeFrame: 48 weeks
Locations:
Study officials:
References: