Using low-dose danazol to treat telomere-related diseases

Low Dose Danazol for the Treatment of Telomere Related Diseases

This study is testing if a low dose of danazol can help improve health in people with telomere-related diseases like aplastic anemia and pulmonary fibrosis.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Ages: 3 Years to 99 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT03312400 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the safety and efficacy of low-dose danazol in patients with telomere-related diseases, which can lead to conditions such as aplastic anemia, pulmonary fibrosis, and hepatic fibrosis. Participants aged 3 and older with specific genetic mutations and symptoms of these diseases will undergo a series of medical evaluations, including blood tests and lung function assessments. The study aims to determine if danazol can improve health outcomes by potentially enhancing telomerase activity and stabilizing telomere length.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 3 and older with very short telomeres and specific gene mutations associated with telomere maintenance.

Not a fit: Patients without telomere-related diseases or those who do not meet the genetic and clinical criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from telomere-related diseases.

How similar studies have performed: Previous studies have shown promising results with androgen treatments in pediatric patients with telomere diseases, suggesting potential for success in this approach.

Eligibility criteria

* INCLUSION CRITERIA:

  1. 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.
  2. 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
  3. Age greater than or equal to 3 years
  4. Weight greater than or equal to 12 Kg

     AND
  5. At least one of the following criteria:

     1. Anemia with a hemoglobin less than or equal to 10 g/dL without red blood cell transfusion
     2. Thrombocytopenia with a platelet count less than or equal to 50,000/microliter without transfusion
     3. 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
  6. 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:

1. Patients on androgen hormones to include testosterone or high dose estrogen (estradiol 0.5 mg/day or greater) for the12 months prior to enrollment
2. Patients with active thrombosis or thromboembolic disease and history of such events, undiagnosed abnormal genital bleeding, porphyria, androgendependent tumor, or prostatic hypertrophy
3. 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.
4. Patients with active hepatitis B or C
5. Patients who have received a bone marrow transplant
6. Patient with other hereditary bone marrow failure syndromes such as Fanconi anemia or Diamond Blackfan anemia
7. Patients with infections not adequately responding to appropriate therapy
8. 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
9. Lactating women, due to the potentially harmful effects on the nursing child
10. Patients with cancer who are actively receiving systemic chemotherapeutic treatment or who take drugs with hematological effects
11. Patients with decompensated liver disease to include persistent ascites, encephalopathy, variceal hemorrhage, or MELD score of 10 or greater
12. 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
13. Inability to swallow a capsule

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Emma M Groarke, M.D. — National Heart, Lung, and Blood Institute (NHLBI)
• Study coordinator: Tania R Machado

Conditions: Telomere Disease, Telomeres, Aplastic Anemia, Pulmonary Fibrosis, Androgens, Hepatic Fibrosis