Ignite Creation Date:
2025-12-24 @ 11:15 PM
Ignite Modification Date:
2026-01-05 @ 6:03 PM
Study NCT ID:
NCT02055456
Status:
COMPLETED
Last Update Posted:
2023-08-31
First Post:
2014-02-03
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Nandrolone Decanoate in the Treatment of Telomeropathies
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000741', 'term': 'Anemia, Aplastic'}, {'id': 'D000080983', 'term': 'Bone Marrow Failure Disorders'}, {'id': 'D054990', 'term': 'Idiopathic Pulmonary Fibrosis'}], 'ancestors': [{'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D011658', 'term': 'Pulmonary Fibrosis'}, {'id': 'D017563', 'term': 'Lung Diseases, Interstitial'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077603', 'term': 'Nandrolone Decanoate'}], 'ancestors': [{'id': 'D009277', 'term': 'Nandrolone'}, {'id': 'D004963', 'term': 'Estrenes'}, {'id': 'D004962', 'term': 'Estranes'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D045165', 'term': 'Testosterone Congeners'}, {'id': 'D012739', 'term': 'Gonadal Steroid Hormones'}, {'id': 'D042341', 'term': 'Gonadal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-02-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-08', 'completionDateStruct': {'date': '2017-02-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-08-28', 'studyFirstSubmitDate': '2014-02-03', 'studyFirstSubmitQcDate': '2014-02-04', 'lastUpdatePostDateStruct': {'date': '2023-08-31', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2014-02-05', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2017-02-01', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Reduction in telomere attrition', 'timeFrame': '2 years', 'description': 'The biologic endpoint is reduction in telomere attrition rate yearly compared to known rates of telomere erosion in normal individuals and in those who carry mutation in the telomerase genes'}], 'secondaryOutcomes': [{'measure': 'Hematologic response', 'timeFrame': '2 years', 'description': 'The hematologic response will be determined by one or more of the following:\n\n1. absolute neutrophil counts (increase of more than 500/μL above initial value)\n2. platelets (increase of more than 20.000/μL above initial value)\n3. Hemoglobin:\n\n * Increase in hemoglobin of more than 1.5 g/dL above initial value OR\n * Transfusion independence in transfusion-dependent patients (more than 2 months without transfusion) OR\n * Reduction of the transfusion needs in more than 50%'}, {'measure': 'Clonal evolution', 'timeFrame': '2 years', 'description': 'Number of participants that evolute to myelodysplasia or acute leukemia.'}, {'measure': 'Improvement in lung function', 'timeFrame': '2 years', 'description': 'The pulmonary response will be determined by the presence of one or more of the following:\n\n1. Improvement of dyspnea severity, objectively evaluated by "Baseline Dyspnea Index";\n2. forced vital capacity (10% absolute increase)\n3. Diffusion of carbon monoxide (DLCO) corrected for hemoglobin (15% increase)\n4. No worsening of pulmonary fibrosis and reduction of assessed ground-glass opacities in computed tomography of the chest'}, {'measure': 'Survival', 'timeFrame': '2 years'}, {'measure': 'Safety', 'timeFrame': '2 years', 'description': 'Number of participants with adverse effects attributed to the use of nandrolone decanoate during the 24 months treatment period.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Hormones', 'Androgens', 'Aplastic Anemia', 'Bone Marrow Failure Syndromes', 'Idiopathic Pulmonary Fibrosis', 'Telomere', 'Telomere Shortening'], 'conditions': ['Aplastic Anemia', 'Bone Marrow Failure Syndromes', 'Idiopathic Pulmonary Fibrosis', 'Telomere Shortening']}, 'referencesModule': {'references': [{'pmid': '16778145', 'type': 'BACKGROUND', 'citation': 'Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood. 2006 Oct 15;108(8):2509-19. doi: 10.1182/blood-2006-03-010777. Epub 2006 Jun 15.'}, {'pmid': '18239083', 'type': 'BACKGROUND', 'citation': 'Calado RT, Young NS. Telomere maintenance and human bone marrow failure. Blood. 2008 May 1;111(9):4446-55. doi: 10.1182/blood-2007-08-019729. Epub 2008 Jan 31.'}, {'pmid': '15814878', 'type': 'BACKGROUND', 'citation': 'Yamaguchi H, Calado RT, Ly H, Kajigaya S, Baerlocher GM, Chanock SJ, Lansdorp PM, Young NS. Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. N Engl J Med. 2005 Apr 7;352(14):1413-24. doi: 10.1056/NEJMoa042980.'}, {'pmid': '19561322', 'type': 'BACKGROUND', 'citation': 'Calado RT, Yewdell WT, Wilkerson KL, Regal JA, Kajigaya S, Stratakis CA, Young NS. Sex hormones, acting on the TERT gene, increase telomerase activity in human primary hematopoietic cells. Blood. 2009 Sep 10;114(11):2236-43. doi: 10.1182/blood-2008-09-178871. Epub 2009 Jun 26.'}, {'pmid': '20007561', 'type': 'BACKGROUND', 'citation': 'Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009 Dec 10;361(24):2353-65. doi: 10.1056/NEJMra0903373. No abstract available.'}, {'pmid': '22476886', 'type': 'BACKGROUND', 'citation': 'Ziegler P, Schrezenmeier H, Akkad J, Brassat U, Vankann L, Panse J, Wilop S, Balabanov S, Schwarz K, Martens UM, Brummendorf TH. Telomere elongation and clinical response to androgen treatment in a patient with aplastic anemia and a heterozygous hTERT gene mutation. Ann Hematol. 2012 Jul;91(7):1115-20. doi: 10.1007/s00277-012-1454-x. Epub 2012 Apr 4.'}, {'pmid': '36579443', 'type': 'DERIVED', 'citation': 'Cle DV, Catto LFB, Gutierrez-Rodrigues F, Donaires FS, Pinto AL, Santana BA, Darrigo LG, Valera ET, Koenigkam-Santos M, Baddini-Martinez J, Young NS, Martinez EZ, Calado RT. Effects of nandrolone decanoate on telomere length and clinical outcome in patients with telomeropathies: a prospective trial. Haematologica. 2023 May 1;108(5):1300-1312. doi: 10.3324/haematol.2022.281808.'}]}, 'descriptionModule': {'briefSummary': 'Decrease in blood cell counts due to deficient bone marrow function, called bone marrow failure, as well as some lung diseases, called idiopathic pulmonary fibrosis, can be caused by genetic defects in telomere biology genes, eventually causing telomere erosion. These disorders are collectively termed "telomeropathies".\n\nThere is evidence that male hormones may improve blood cell counts in marrow failure, and these hormones are able to stimulate telomerase function in hematopoietic cells in vitro. We propose this study to the use of male hormone in patients with aplastic anemia and pulmonary fibrosis associated with defects in telomeres.', 'detailedDescription': 'Telomeres are repeated nucleotide sequences of non-coding DNA at the ends of chromosomes that have protective functions and avoid chromosomes recombinations and fusions.\n\nLoss-of-function mutations in genes of the telomerase complex, a enzyme responsible for maintaining telomere length, has been associated with bone marrow failures, notedly mutations in DKC1 gene, detected in a rare inherited form of marrow aplasia, called dyskeratosis congenita. These findings implicated telomerase dysfunction and shortening telomere length in failed hematopoiesis.\n\nIn family members of probands with aplastic anemia, marrow aplasia and telomerase mutations also have been observed and associated to varying degrees of cytopenias, IPF and/or cirrhosis. Moreover, patients with varying degrees of cytopenias, with significant family history for cytopenias, IPF and/or cirrhosis, have been identified with very short telomeres and some mutations in telomerase complex genes. Additionally, telomere length has been associated with human cancer.\n\nIn vitro studies suggest that telomere length could be modulated with sex hormones. Normal lymphocytes and human bone marrow progenitor cells exposed to androgens increased telomerase activity in vitro, and in individuals with telomerase mutations (TERT) androgens increased telomerase activity.This could be the explanation for the hematologic improvement observed in some aplastic anemia patients treated over 40 years ago with male hormones.\n\nTherefore, we hypothesize that androgens therapy might modulate telomere attrition in vivo and ameliorate progression or reverse the clinical consequences of shortening telomere length, and we propose androgens therapy in patients with cytopenias and/or IPF with a short age adjusted telomere length, with or without telomerase gene mutations.\n\nThe primary biologic endpoint will be the reduction of telomere attrition over time compared to known rates of telomere erosion in normal individuals and in those who carry mutation in the telomerase genes. Secondary endpoints will be tolerability of nandrolone decanoate over two years, improvement in blood counts and/or pulmonary function.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '2 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Peripheral blood leukocytes telomeres short for age, below the first percentile of a curve based on 500 healthy individuals between 0 and 100 years, with or without a telomerase gene mutation.\n\nAND\n\n* One or more of the following cytopenias:\n\nAnemia (symptoms of anemia with hemoglobin \\<9.5 g/dL, or need for transfusion \\> 2 units of packed red blood cells/month for at least two months, or absolute reticulocytes count \\<60.000/μL).\n\nThrombocytopenia (platelets counts \\<30.000/μL or \\<50.000/μL associated with bleeding, or megakaryocytes reduction in the bone marrow).\n\nNeutropenia (absolute neutrophil counts \\<1.000/μL).\n\nOR\n\n* Idiopathic pulmonary fibrosis diagnosed according to the American Thoracic Society (ATS) criteria.\n\nExclusion Criteria:\n\n* Terminal disease or liver disease, renal, cardiac, neurological, infectious or concomitant metabolic state whose gravity prevents the ability of the patient to tolerate the treatment protocol, or probable death within 30 days.\n* People with cancer who are undergoing chemotherapy.\n* Pregnancy, or desire to not prevent pregnancy in childbearing age.\n* Aplastic Anemia patients with indication for bone marrow transplantation and matched donor.'}, 'identificationModule': {'nctId': 'NCT02055456', 'briefTitle': 'Nandrolone Decanoate in the Treatment of Telomeropathies', 'organization': {'class': 'OTHER', 'fullName': 'University of Sao Paulo'}, 'officialTitle': 'Male Hormones for Telomere Related Diseases', 'orgStudyIdInfo': {'id': '11-H-RTC-0002'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Nandrolone Decanoate', 'description': 'Nandrolone Decanoate intramuscularly administered, every two weeks, 5 mg/kg/dose', 'interventionNames': ['Drug: Nandrolone Decanoate']}], 'interventions': [{'name': 'Nandrolone Decanoate', 'type': 'DRUG', 'armGroupLabels': ['Nandrolone Decanoate']}]}, 'contactsLocationsModule': {'locations': [{'zip': '14048-900', 'city': 'Ribeirão Preto', 'state': 'São Paulo', 'country': 'Brazil', 'facility': 'Ribeirao Preto School of Medicine, University of Sao Paulo', 'geoPoint': {'lat': -21.1775, 'lon': -47.81028}}], 'overallOfficials': [{'name': 'Rodrigo T Calado, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Ribeirao Preto School of Medicine at University of Sao Paulo'}, {'name': 'Diego V Clé, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ribeirao Preto School of Medicine at University of Sao Paulo'}, {'name': 'Ana Beatriz Hortense, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Ribeirao Preto School of Medicine at University of Sao Paulo'}, {'name': 'José Antonio Baddini Martinez, MD, PhD', 'role': 'STUDY_CHAIR', 'affiliation': 'Ribeirao Preto School of Medicine at University of Sao Paulo'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Sao Paulo', 'class': 'OTHER'}, 'collaborators': [{'name': 'Conselho Nacional de Desenvolvimento Científico e Tecnológico', 'class': 'OTHER_GOV'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD', 'investigatorFullName': 'Diego Villa Clé', 'investigatorAffiliation': 'University of Sao Paulo'}}}}