Status:
RECRUITING
Low-Dose Danazol for the Treatment of Telomere Related Diseases
Lead Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Conditions:
Telomere Disease
Eligibility:
All Genders
3-99 years
Phase:
PHASE2
Brief Summary
Background: DNA is a structure in the body. It contains data about how the body develops and works. Telomeres are found on the end of chromosomes in DNA. Some people with short telomeres or other gen...
Detailed Description
Telomere disease is caused by accelerated telomere attrition and results in multi-organ dysfunction. Telomeres are nucleotide repeats of non-coding DNA at the end of the chromosomes which function as ...
Eligibility Criteria
Inclusion
- INCLUSION CRITERIA:
- Age-adjusted telomere length less than or equal to the first percentile by flow-FISH method. In patients with a known pathogenic or likely pathogenic mutation in a telomere maintenance gene, age adjusted telomere length less than or equal to the 10th percentile is sufficient.
- A mutation in telomere maintenance genes (TERT, TERC, DKC1, TINF2, NHP2, NOP10, WRAP53, TERF2, PARN, RTEL1, ACD, CTC1, USB1) as tested in a CLIA (or international equivalent) certified laboratory
- Age greater than or equal to 3 years
- Weight greater than or equal to 12 Kg
- AND
- At least one of the following criteria:
- Anemia with a hemoglobin less than or equal to 10 g/dL without red blood cell transfusion
- Thrombocytopenia with a platelet count less than or equal to 50,000/microliter without transfusion
- Neutropenia with an absolute neutrophil count less than or equal to 1,000/ microliter
- OR
- Pulmonary fibrosis diagnosed by either a lung biopsy or computed tomography scan of the chest according to guidelines from the American Thoracic Society and European Respiratory Society.
- OR
- Hepatic fibrosis diagnosed by Transient Elastography by Fibroscan value greater than 10 kpa or US evidence of cirrhotic liver or splenomegaly, or transjugular liver biopsy demonstrating fibrosis.
- EXCLUSION CRITERIA:
- Patients on androgen hormones to include testosterone or high dose estrogen (estradiol 0.5 mg/day or greater) for the12 months prior to enrollment
- Patients with active thrombosis or thromboembolic disease and history of such events, undiagnosed abnormal genital bleeding, porphyria, androgendependent tumor, or prostatic hypertrophy
- Patients with pulmonary fibrosis who are receiving anti-fibrotic drug treatment, such as pirfenidone or nintedanib unless stable on anti-fibrotic drug for at least 6 months prior to starting on danazol as demonstrated by PFTs.
- Patients with active hepatitis B or C
- Patients who have received a bone marrow transplant
- Patient with other hereditary bone marrow failure syndromes such as Fanconi anemia or Diamond Blackfan anemia
- Patients with infections not adequately responding to appropriate therapy
- Current pregnancy, or unwillingness to take oral contraceptives or use the barrier methods 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 cancer who are actively receiving systemic chemotherapeutic treatment or who take drugs with hematological effects
- Patients with decompensated liver disease to include persistent ascites, encephalopathy, variceal hemorrhage, or MELD score of 10 or greater
- Inability to understand the investigational nature of the study or to give informed consent or without a legally authorized representative or surrogate that can provide informed consent
- Inability to swallow a capsule
Exclusion
Key Trial Info
Start Date :
February 8 2018
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
October 29 2027
Estimated Enrollment :
40 Patients enrolled
Trial Details
Trial ID
NCT03312400
Start Date
February 8 2018
End Date
October 29 2027
Last Update
December 17 2025
Active Locations (1)
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1
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892