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Trial record 1 of 1 for:    Nandrolone Decanoate in the Treatment of Telomeropathies
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Nandrolone Decanoate in the Treatment of Telomeropathies

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ClinicalTrials.gov Identifier: NCT02055456
Recruitment Status : Unknown
Verified December 2015 by Diego Villa Clé, University of Sao Paulo.
Recruitment status was:  Recruiting
First Posted : February 5, 2014
Last Update Posted : December 2, 2015
Sponsor:
Collaborator:
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Information provided by (Responsible Party):
Diego Villa Clé, University of Sao Paulo

Brief Summary:

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".

There 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.


Condition or disease Intervention/treatment Phase
Aplastic Anemia Bone Marrow Failure Syndromes Idiopathic Pulmonary Fibrosis Telomere Shortening Drug: Nandrolone Decanoate Phase 1 Phase 2

Detailed Description:

Telomeres are repeated nucleotide sequences of non-coding DNA at the ends of chromosomes that have protective functions and avoid chromosomes recombinations and fusions.

Loss-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.

In 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.

In 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.

Therefore, 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.

The 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Male Hormones for Telomere Related Diseases
Study Start Date : February 2014
Estimated Primary Completion Date : February 2017
Estimated Study Completion Date : February 2017


Arm Intervention/treatment
Experimental: Nandrolone Decanoate
Nandrolone Decanoate intramuscularly administered, every two weeks, 5 mg/kg/dose
Drug: Nandrolone Decanoate



Primary Outcome Measures :
  1. Reduction in telomere attrition [ Time Frame: 2 years ]
    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


Secondary Outcome Measures :
  1. Hematologic response [ Time Frame: 2 years ]

    The hematologic response will be determined by one or more of the following:

    1. absolute neutrophil counts (increase of more than 500/μL above initial value)
    2. platelets (increase of more than 20.000/μL above initial value)
    3. Hemoglobin:

      • Increase in hemoglobin of more than 1.5 g/dL above initial value OR
      • Transfusion independence in transfusion-dependent patients (more than 2 months without transfusion) OR
      • Reduction of the transfusion needs in more than 50%

  2. Clonal evolution [ Time Frame: 2 years ]
    Number of participants that evolute to myelodysplasia or acute leukemia.

  3. Improvement in lung function [ Time Frame: 2 years ]

    The pulmonary response will be determined by the presence of one or more of the following:

    1. Improvement of dyspnea severity, objectively evaluated by "Baseline Dyspnea Index";
    2. forced vital capacity (10% absolute increase)
    3. Diffusion of carbon monoxide (DLCO) corrected for hemoglobin (15% increase)
    4. No worsening of pulmonary fibrosis and reduction of assessed ground-glass opacities in computed tomography of the chest

  4. Survival [ Time Frame: 2 years ]
  5. Safety [ Time Frame: 2 years ]
    Number of participants with adverse effects attributed to the use of nandrolone decanoate during the 24 months treatment period.



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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

AND

  • One or more of the following cytopenias:

Anemia (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).

Thrombocytopenia (platelets counts <30.000/μL or <50.000/μL associated with bleeding, or megakaryocytes reduction in the bone marrow).

Neutropenia (absolute neutrophil counts <1.000/μL).

OR

  • Idiopathic pulmonary fibrosis diagnosed according to the American Thoracic Society (ATS) criteria.

Exclusion Criteria:

  • 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.
  • People with cancer who are undergoing chemotherapy.
  • Pregnancy, or desire to not prevent pregnancy in childbearing age.
  • Aplastic Anemia patients with indication for bone marrow transplantation and matched donor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02055456


Contacts
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Contact: Diego V Clé, MD +55 16 36022294 diegocle@yahoo.com
Contact: Rodrigo T Calado, MD, PhD +55 16 36022169 rtcalado@fmrp.usp.br

Locations
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Brazil
Ribeirao Preto School of Medicine, University of Sao Paulo Recruiting
Ribeirao Preto, Sao Paulo, Brazil, 14048-900
Sponsors and Collaborators
University of Sao Paulo
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Investigators
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Study Chair: Rodrigo T Calado, MD, PhD Ribeirao Preto School of Medicine at University of Sao Paulo
Principal Investigator: Diego V Clé, MD Ribeirao Preto School of Medicine at University of Sao Paulo
Principal Investigator: Ana Beatriz Hortense, MD Ribeirao Preto School of Medicine at University of Sao Paulo
Study Chair: José Antonio Baddini Martinez, MD, PhD Ribeirao Preto School of Medicine at University of Sao Paulo

Publications:
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Responsible Party: Diego Villa Clé, MD, University of Sao Paulo
ClinicalTrials.gov Identifier: NCT02055456     History of Changes
Other Study ID Numbers: 11-H-RTC-0002
First Posted: February 5, 2014    Key Record Dates
Last Update Posted: December 2, 2015
Last Verified: December 2015

Keywords provided by Diego Villa Clé, University of Sao Paulo:
Hormones
Androgens
Aplastic Anemia
Bone Marrow Failure Syndromes
Idiopathic Pulmonary Fibrosis
Telomere
Telomere Shortening

Additional relevant MeSH terms:
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Nandrolone Decanoate
Nandrolone
Nandrolone phenpropionate
Pulmonary Fibrosis
Idiopathic Pulmonary Fibrosis
Idiopathic Interstitial Pneumonias
Anemia, Aplastic
Pancytopenia
Hemoglobinuria, Paroxysmal
Fibrosis
Pathologic Processes
Anemia
Hematologic Diseases
Lung Diseases
Respiratory Tract Diseases
Lung Diseases, Interstitial
Bone Marrow Diseases
Anemia, Hemolytic
Myelodysplastic Syndromes
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Androgens
Anabolic Agents
Bone Density Conservation Agents