PRETELL: PREvention of TELomere-related Complications After Lung Transplant

NCT04807309 | Withdrawn Phase 1 DMC FDA Drug

• 1 other identifier: 2021P000271
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Short Telomere Length; Lung Transplant

Keywords

Danazol; Short telomere; Lung transplant; Prevention; Leukopenia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Occurrence of WBC <2000/µl

  48 weeks

• Cumulative number of events where WBC < 2000/µl

  48 weeks

Other Outcomes (1)

• Telomere length

  48 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo comparison

Drug: Placebo

Danazol Pill

ACTIVE COMPARATOR

Danazol 200mg orally twice a day

Drug: Danazol Pill

Interventions

Danazol Pill DRUG

Danazol 200 mg orally twice a day

Danazol Pill

Placebo DRUG

Placebo twice a day

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead

MeSH Terms

Conditions

Leukopenia

Interventions

Danazol

Condition Hierarchy (Ancestors)

Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders

Intervention Hierarchy (Ancestors)

Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Similar tablets will be generated.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Physician

Model Details: Randomized double blind 2:1 ratio

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 19, 2021
• Study Start: January 1, 2021
• Primary Completion: November 20, 2021
• Study Completion: January 1, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share