PRETELL: PREvention of TELomere-related Complications After Lung Transplant (PRETELL)

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.

Study Overview

• Status: Withdrawn
• Conditions: Lung Transplant; Short Telomere Length
• Intervention / Treatment: Drug: Placebo; Drug: Danazol Pill

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo comparison	Drug: Placebo; Placebo twice a day
Active Comparator: Danazol Pill; Danazol 200mg orally twice a day	Drug: Danazol Pill; Danazol 200 mg orally twice a day

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Telomere length	-Measure change in lymphocyte telomere length at end of study drug administration compared to screening	48 weeks

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2021
• Primary Completion (Actual): November 20, 2021
• Study Completion (Actual): January 1, 2022

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 17, 2021
• First Posted (Actual): March 19, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2023
• Last Update Submitted That Met QC Criteria: February 12, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Prevention; Lung transplant; Leukopenia; Danazol; Short telomere
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: 2021P000271

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No