Evidence map›Paper›PMID 27192671›Full record

Trial reportThe New England journal of medicine2016

Danazol Treatment for Telomere Diseases.

Danielle M Townsley, Bogdan Dumitriu, Delong Liu, Angélique Biancotto, Barbara Weinstein, Christina Chen, Nathan Hardy, Andrew D Mihalek, Shilpa Lingala, Yun Ju Kim and 8 more

2 registry-linked trialsOpen access · bronzeAbstract readClinical Trial, Phase IClinical Trial, Phase II
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 187 papers.

0numbers the graph read from it
0cells of the map it votes in
187citing papers in PubMed
29.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01441037 phase1 / phase2completednot on this map

Male Hormones for Telomere Related Diseases

TypeinterventionalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2011 to 2016Enrolled27ConditionsAplastic AnemiaArmsDanazol
NCT03312400 phase2completednot on this mapstarted 2018, after this paper: background citation

Low Dose Danazol for the Treatment of Telomere Related Diseases

TypeinterventionalSponsorNational Heart, Lung, and Blood Institute (NHLBI)Ran2018 to 2025Enrolled18ConditionsTelomere DiseaseArmsDanazol
3 · Its place in the literature

Who cites it

187 citing papers in PubMed, 396 citations in OpenAlex.

  1. Trial
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Trial
  7. The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review

127 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 5 institutions in 1 country.

Danielle M TownsleyFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Bogdan DumitriuFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Delong LiuFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Angélique BiancottoFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Barbara WeinsteinFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Christina ChenFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Nathan HardyFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Andrew D MihalekFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Shilpa LingalaFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Yun Ju KimFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Jianhua YaoFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Elizabeth JonesFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Bernadette R GochuicoFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Theo HellerFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Colin O WuFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Rodrigo T CaladoFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Phillip ScheinbergFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
Neal S YoungFrom the Hematology Branch (D.M.T., B.D., D.L., B.W., C.C., N.H., N.S.Y.), the Cardiopulmonary Branch (A.D.M.), and the Office of Biostatistics Research (C.O.W.), National Heart, Lung, and Blood Institute, the Center for Human Immunology, Autoimmunity, and Inflammation (A.B.), the Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases (S.L., Y.J.K., T.H.), Radiology and Imaging Sciences, Clinical Center (J.Y., E.J.), and the Medical Genetics Branch, National Human Genome Research Institute (B.R.G.), National Institutes of Health, Bethesda, MD; and the Department of Internal Medicine, University of São Paulo at Ribeirão Preto Medical School, Ribeirão Preto (R.T.C.), and Clinical Hematology, Antônio Ermírio de Moraes Cancer Center, Hospital São José and Beneficência Portuguesa (P.S.), São Paulo.
National Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · USCancer Research And Biostatistics · USNational Heart Lung and Blood Institute · USNational Human Genome Research Institute · US

Funding

Telomeres DiseasesZIAHL006089 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI YOUNG, NEAL S · 2010 to 2025
$26.2M
Investigation of non-cirrhotic portal hypertension.ZIADK075008 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI HELLER, THEO · 2009 to 2025
$4.5M
Intramural NIH HHS Z99 HL999999
6 · The paper itself

Abstract

backgroundGenetic defects in telomere maintenance and repair cause bone marrow failure, liver cirrhosis, and pulmonary fibrosis, and they increase susceptibility to cancer. Historically, androgens have been useful as treatment for marrow failure syndromes. In tissue culture and animal models, sex hormones regulate expression of the telomerase gene.

methodsIn a phase 1-2 prospective study involving patients with telomere diseases, we administered the synthetic sex hormone danazol orally at a dose of 800 mg per day for a total of 24 months. The goal of treatment was the attenuation of accelerated telomere attrition, and the primary efficacy end point was a 20% reduction in the annual rate of telomere attrition measured at 24 months. The occurrence of toxic effects of treatment was the primary safety end point. Hematologic response to treatment at various time points was the secondary efficacy end point.

resultsAfter 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 end point; in the intention-to-treat analysis, 12 of 27 patients (44%; 95% confidence interval [CI], 26 to 64) met the primary efficacy end point. Unexpectedly, almost all the patients (11 of 12, 92%) had a gain in telomere length at 24 months as compared with baseline (mean increase, 386 bp [95% CI, 178 to 593]); in exploratory analyses, similar increases were observed at 6 months (16 of 21 patients; mean increase, 175 bp [95% CI, 79 to 271]) and 12 months (16 of 18 patients; mean increase, 360 bp [95% CI, 209 to 512]). Hematologic responses occurred in 19 of 24 patients (79%) who could be evaluated at 3 months and in 10 of 12 patients (83%) who could be evaluated at 24 months. Known adverse effects of danazol--elevated liver-enzyme levels and muscle cramps--of grade 2 or less occurred in 41% and 33% of the patients, respectively.

conclusionsIn our study, treatment with danazol led to telomere elongation in patients with telomere diseases. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01441037.).

Indexed as

Administration, OralAdolescentAdultAgedBone Marrow DiseasesDanazolEstrogen AntagonistsFemaleHair ColorHumansLiver CirrhosisMaleMiddle AgedMutationProspective StudiesPulmonary FibrosisDanazolEstrogen AntagonistsTelomerase

Identifiers

PMID27192671
PMCPMC4968696
OpenAlexW2394724717

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.