RECRUITING

Low-Dose Danazol for the Treatment of Telomere Related Diseases

Conditions

Telomere Disease Telomeres Aplastic Anemia Pulmonary Fibrosis Androgens Hepatic Fibrosis

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 gene changes can develop diseases of the bone marrow, lung, and liver. Researchers want to see if low doses of the hormone drug danazol can help. Objective: To study the safety and effect of low dose danazol. Eligibility: People ages 3 and older with a telomere disease who have either very short telomeres and a specific gene change. They must also show signs of aplastic anemia, lung, or liver disease. Design: Participants will be screened in another protocol. Participants will have: * Medical history * Physical exam * Blood tests * Lung exam. They will breathe into an instrument that records the amount and rate of air breathed in and out over a period of time. 6-minute walking test. * Abdominal ultrasound and liver scan. These tests use sound waves to measure the fibrosis in the liver. Some participants will have: * Pregnancy test * Small sample of the liver removed * Bone marrow biopsy. The bone will be numbed and a small needle will take a sample of the marrow. All participants will have hormone levels checked. All child participants will see a pediatric endocrinologist. Children may need to have a hand x-ray. We will monitor patients for 6 months before starting danazol. Participants will take danazol by mouth twice a day for 1 year. Participants must return to the clinic at 6 months and 12 months while on danazol and 6 months after stopping it. They will have blood and urine tests, a lung exam, abdominal ultrasound, and liver scan.

Official Title

Low Dose Danazol for the Treatment of Telomere Related Diseases

Quick Facts

Study Start:2018-02-08

Study Completion:2027-10-29

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03312400

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:3 Years to 99 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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 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.	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

Inclusion Criteria

Exclusion 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
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
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.

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

Contacts and Locations

Study Contact

Tania R Machado

CONTACT

(301) 661-1505

tania.machado@nih.gov

Emma M Groarke, M.D.

CONTACT

(301) 496-5093

emma.groarke@nih.gov

Principal Investigator

Emma M Groarke, M.D.

PRINCIPAL_INVESTIGATOR

National Heart, Lung, and Blood Institute (NHLBI)

Study Locations (Sites)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892

United States

Collaborators and Investigators

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Emma M Groarke, M.D., PRINCIPAL_INVESTIGATOR, National Heart, Lung, and Blood Institute (NHLBI)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-02-08

Study Completion Date2027-10-29

Study Record Updates

Study Start Date2018-02-08

Study Completion Date2027-10-29

Terms related to this study

Keywords Provided by Researchers

Telomeres
Aplastic Anemia
Pulmonary Fibrosis
Androgens
Hepatic Fibrosis

Additional Relevant MeSH Terms

Telomere Disease