PRETELL: PREvention of TELomere-related Complications After Lung Transplant

Phase 1

Withdrawn

• Conditions: Lung Transplant; Short Telomere Length
• Interventions: Drug: Placebo; Drug: Danazol Pill

• Registration Number: NCT04807309
• Lead Sponsor: Brigham and Women's Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-01
• Study First Submitted: 2021-03-15
• Study First Submitted QC: 2021-03-17
• Study First Posted: 2021-03-19
• Primary Completion: 2021-11-20
• Study Completion: 2022-01-01
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-12
• Last Update Posted: 2023-02-15

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo comparison
Danazol Pill	Danazol Pill	Danazol 200mg orally twice a day

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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