A Phase 2 interventional study of Danazol in Telomere Disease, sponsored by National Heart, Lung, and Blood Institute (NHLBI). Terminated at 1 site in United States. Open to participants aged 3 Years to 99 Years. Per ClinicalTrials.gov, last updated 2026-10-27.
Sponsored by National Heart, Lung, and Blood Institute (NHLBI) · Phase 2, Interventional, and Treatment
Study was stopped due to poor accrual
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:
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.
Some participants will have:
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.
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 protective caps to prevent erosion of genomic DNA during cell division and to protect chromosomes from recognition as single stranded DNA. Telomeric DNA is elongated by the telomerase complex, which is comprised of a reverse transcriptase catalytic subunit (encoded by TERT), an RNA template (encoded by TERC) and associated proteins.
Telomerase activity is crucial in maintaining telomere length in cells with a high proliferative capacity, such as hematopoietic stem cells (HSCs) and lymphocytes. Presentation of telomeropathies can vary from severe aplastic anemia (SAA) and dyskeratosis congenital (DKC) early in childhood, to pulmonary or hepatic fibrosis later in life. There is no standard of care for the treatment of telomere disease.
Considerable evidence suggests that sex hormones regulate telomerase. Calado et al. demonstrated that human lymphocytes and CD34+ hematopoietic cells up regulate both TERT gene expression and telomerase enzymatic activity in response to androgens in vitro. A recent observational cohort study demonstrated hematologic response in 14 of 16 pediatric patients with DKC treated with androgens. In a prospective trial from our Branch, Townsley et al demonstrated that patients with telomere diseases who were treated with the synthetic sex hormone danazol showed telomere elongation, and hematologic response were seen in 79% of patients after only three months of treatment. This study used the highest dose of danazol, 800 mg daily, and known adverse effects, such as elevated liver enzyme levels and muscle cramps, occurred in 41% and 33% of patients, respectively. Overall the treatment was well tolerated, but some patients did require dose reduction. After 27 patients were enrolled, the study was halted early, because telomere attrition was reduced in all 12 patients who could be evaluated for the primary endpoint. Because of the limited power, we were unable to draw definitive conclusions regarding further clinical effect of danazol but stabilization or improvement was observed in a few cases in other organ function, measured by DLCO for pulmonary fibrosis and Fibroscan for cirrhosis.
We now propose a phase II study designed to determine the efficacy of low dose danazol in decreasing the rate of telomere attrition in subjects with a short age-adjusted telomere length. The secondary aim is to determine the clinical effect of this therapy in conditions that are related to short telomeres, to include cytopenia(s), pulmonary fibrosis, and/or hepatic fibrosis.
371 studies on the registry are indexed under Anemia, Aplastic; 98 are open to participants now.
This study's enrollment of 18 is below the median of 37 across 281 interventional studies indexed under Anemia, Aplastic.
Browse Anemia, Aplastic studies →National Heart, Lung, and Blood Institute (NHLBI) is the lead sponsor of 1,143 studies on the registry; 71 are open to participants now.
Of its 58 completed or terminated interventional studies of FDA-regulated products, 51 (88%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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.
Weight greater than or equal to 12 Kg
AND
At least one of the following criteria:
OR
Pulmonary fibrosis diagnosed by either a lung or computed tomography scan of the chest according to guidelines from the American Thoracic Society and European Respiratory Society.
OR
EXCLUSION CRITERIA:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive danazol 100 mg twice daily for the first 24 weeks. At Week 24, the dose will be increased to 200 mg twice daily.
Drug: Danazol
Participants will receive danazol 200 mg twice daily for the first 24 weeks. At Week 24, the dose will be reduced to 100 mg twice daily.
Drug: Danazol
Participants will be randomized to one of two treatment arms, and after 6 months of treatment they will switch to the other treatment arm. One arm will be danazol 100 mg twice a day, the other arm will be danazol 200 mg twice a day. Every patient will receive 6 months danazol 200 mg/day and 6 months 400 mg/day, thereby completing 12 months of danazol treatment. Pediatric participants less than 50 kg will be dosed at 4 or 8 mg/kg/day not to exceed 200 or 400 mg/day, respectively.
Number of Participants With a Reduction in Telomere Attrition Rate at 6 Months
Telomere attrition rate will be compared between participants receiving danazol 400 mg and 200 mg. A reduction in telomere attrition rate is defined as a ≥50% reduction from baseline.
Time frame: Baseline, 24 Weeks
Hematologic Response
Response is if on at least two serial measures one week apart: * Participant with severe pancytopenia, defined as Absolute neutrophil count (ANC) \<500/μL , platelet count \<20,000/μL, and reticulocyte count \<20, 000, will be considered to have a response when criteria is no longer for at least 2 of the following criteria: Absolute neutrophil count \>500/μL; Platelet count \> 20,000/μL; Reticulocyte count \> 60,000/μL * Participants with moderate pancytopenia, or those not qualified as severe, response is defined as improvement in one or more of the below: * If baseline ANC is below 500/μL, increase in ANC greater or equal to 300/μL * If baseline ANC is above 500/μL, increase in ANC greater or equal to 500/μL * If platelet response is increased by greater or equal to 20,000/μL * If any increase in hemoglobin by 1.5 g/dL of blood in transfusion independent participants and in absolute reticulocyte count to greater or equal to 60,000 /μL of blood in transfusion-dependent patients
Time frame: 6 and 12 months
Pulmonary Function Testing Response in Participants With Pulmonary Fibrosis
Defined as a positive response of the rate of Forced vital capacity (FVC) decline on drug is 5% less than baseline rate of decline.
Time frame: After 6 and 12 months of treatment
Hepatic Response in Participants With Hepatic Fibrosis
Defined as improvement in one or more of the listed parameters: 1. Reduction in transient elastography by Fibroscan of greater or equal to 20% OR 2. Reduction in hepatic venous portal gradient by greater or equal to 20% in subjects who had liver biopsy for significant liver disease. OR 3. Reduction in transient elastography by Acoustic Radiation Force Impulse imaging greater or equal to 20%.
Time frame: After 6 and 12 months of treatment
Proportion of Adverse Events, Including Serious Adverse Events (SAEs) and Treatment Related SAEs
Proportion of adverse events, including serious adverse events (SAEs) and treatment related SAEs using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. CTCAE grades side effects from 1 to 5: mild, moderate, severe, life-threatening, or fatal.
Time frame: 12 months
| Milestone | Danazol 400 mg Then Danazol 200 mg | Danazol 200 mg Then Danazol 400 mg |
|---|---|---|
| Started | 10 | 8 |
| Completed | 9 | 8 |
| Not completed | 1 | 0 |
| Withdrew: Adverse event | 1 | 0 |
| Milestone | Danazol 400 mg Then Danazol 200 mg | Danazol 200 mg Then Danazol 400 mg |
|---|---|---|
| Started | 9 | 8 |
| Completed | 8 | 8 |
| Not completed | 1 | 0 |
| Withdrew: Physician decision | 1 | 0 |
| Milestone | Danazol 400 mg Then Danazol 200 mg | Danazol 200 mg Then Danazol 400 mg |
|---|---|---|
| Started | 8 | 8 |
| Completed | 7 | 8 |
| Not completed | 1 | 0 |
| Withdrew: Lost to follow-up | 1 | 0 |
Telomere attrition rate will be compared between participants receiving danazol 400 mg and 200 mg. A reduction in telomere attrition rate is defined as a ≥50% reduction from baseline.
| Participants | Danazol 200 mg | Danazol 400 mg |
|---|---|---|
| Response to Reduction in Telomere Attrition Rate by 50% | 5 | 5 |
| Non-responder to Reduction in Telomere Attrition Rate by 50% | 3 | 5 |
Response is if on at least two serial measures one week apart: * Participant with severe pancytopenia, defined as Absolute neutrophil count (ANC) \<500/μL , platelet count \<20,000/μL, and reticulocyte count \<20, 000, will be considered to have a response when criteria is no longer for at least 2 of the following criteria: Absolute neutrophil count \>500/μL; Platelet count \> 20,000/μL; Reticulocyte count \> 60,000/μL * Participants with moderate pancytopenia, or those not qualified as severe, response is defined as improvement in one or more of the below: * If baseline ANC is below 500/μL, increase in ANC greater or equal to 300/μL * If baseline ANC is above 500/μL, increase in ANC greater or equal to 500/μL * If platelet response is increased by greater or equal to 20,000/μL * If any increase in hemoglobin by 1.5 g/dL of blood in transfusion independent participants and in absolute reticulocyte count to greater or equal to 60,000 /μL of blood in transfusion-dependent patients
Results for this outcome have not been posted.
Defined as a positive response of the rate of Forced vital capacity (FVC) decline on drug is 5% less than baseline rate of decline.
Results for this outcome have not been posted.
Defined as improvement in one or more of the listed parameters: 1. Reduction in transient elastography by Fibroscan of greater or equal to 20% OR 2. Reduction in hepatic venous portal gradient by greater or equal to 20% in subjects who had liver biopsy for significant liver disease. OR 3. Reduction in transient elastography by Acoustic Radiation Force Impulse imaging greater or equal to 20%.
Results for this outcome have not been posted.
Proportion of adverse events, including serious adverse events (SAEs) and treatment related SAEs using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. CTCAE grades side effects from 1 to 5: mild, moderate, severe, life-threatening, or fatal.
Results for this outcome have not been posted.
Collected over Up to 18 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Danazol 200 mg | 0/16 (0%) | 1/16 (6.3%) | 9/16 (56.3%) |
| Danazol 400 mg | 0/18 (0%) | 1/18 (5.6%) | 10/18 (55.6%) |
| Off Treatment - Follow Up | 0/16 (0%) | 3/16 (18.8%) | 6/16 (37.5%) |
| Event | Danazol 200 mg | Danazol 400 mg | Off Treatment - Follow Up |
|---|---|---|---|
| Lung TransplantSurgical and medical procedures | 0/16 | 0/18 | 2/16 |
| Suicide attemptPsychiatric disorders | 0/16 | 0/18 | 1/16 |
| acute hypoxic respiratory failureRespiratory, thoracic and mediastinal disorders | 0/16 | 0/18 | 1/16 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 0/16 | 0/18 | 1/16 |
| Chest pain - cardiacCardiac disorders | 1/16 | 0/18 | 0/16 |
| UrticariaSkin and subcutaneous tissue disorders | 0/16 | 1/18 | 0/16 |
| Event | Danazol 200 mg | Danazol 400 mg | Off Treatment - Follow Up |
|---|---|---|---|
| Alanine aminotransferase increasedInvestigations | 1/16 | 3/18 | 0/16 |
| HeadacheNervous system disorders | 2/16 | 2/18 | 0/16 |
| Upper respiratory infectionRespiratory, thoracic and mediastinal disorders | 2/16 | 0/18 | 0/16 |
| Gastroesophageal reflux diseaseGastrointestinal disorders | 0/16 | 2/18 | 0/16 |
| AlopeciaSkin and subcutaneous tissue disorders | 0/16 | 0/18 | 1/16 |
| AscitesGastrointestinal disorders | 0/16 | 0/18 | 1/16 |
| Back painMusculoskeletal and connective tissue disorders | 0/16 | 0/18 | 1/16 |
| Blood bilirubin increasedInvestigations | 0/16 | 1/18 | 1/16 |
| DepressionPsychiatric disorders | 0/16 | 0/18 | 1/16 |
| DiabetesEndocrine disorders | 1/16 | 0/18 | 0/16 |
| Age, Categorical(Participants) | Danazol 200 mg Then Danazol 400 mg | Danazol 400 mg Then Danazol 200 mg | Total |
|---|---|---|---|
| <=18 years | 0 | 2 | 2 |
| Between 18 and 65 years | 8 | 7 | 15 |
| >=65 years | 0 | 1 | 1 |
| Sex: Female, Male(Participants) | Danazol 200 mg Then Danazol 400 mg | Danazol 400 mg Then Danazol 200 mg | Total |
|---|---|---|---|
| Female | 4 | 3 | 7 |
| Male | 4 | 7 | 11 |
| Race (NIH/OMB)(Participants) | Danazol 200 mg Then Danazol 400 mg | Danazol 400 mg Then Danazol 200 mg | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 1 | 1 |
| White | 8 | 9 | 17 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Ethnicity (NIH/OMB)(Participants) | Danazol 200 mg Then Danazol 400 mg | Danazol 400 mg Then Danazol 200 mg | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 1 |
| Not Hispanic or Latino | 8 | 9 | 17 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(Participants) | Danazol 200 mg Then Danazol 400 mg | Danazol 400 mg Then Danazol 200 mg | Total |
|---|---|---|---|
| United States | 8 | 10 | 18 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — IPD used in the results publication will be shared
Access criteria: Individual controlled access data will be shared through dbGAP
Study was stopped due to poor accrual
Study was stopped due to poor accrual
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Danazol
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