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Aplastic AnemiaPhase 1/2NCT02055456

Nandrolone Decanoate in the Treatment of Telomeropathies

A Phase 1/2 study testing Nandrolone Decanoate in people with Aplastic Anemia and Bone Marrow Failure Syndromes, run by University of Sao Paulo at 1 site in Brazil.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 2 to 99 years
What is being tested?
Nandrolone Decanoate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteBrazil
Study dates
1 Feb 2014to 1 Feb 2017
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 2 to 99 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Brazil1 site

  • Ribeirao Preto School of Medicine, University of Sao Paulo

    Ribeirão Preto, São Paulo, 14048-900

Other trials in Brazil

About this study

Official title: Male Hormones for Telomere Related Diseases

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.

Read the 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.

Being tested
Nandrolone Decanoate
Keywords
Hormones, Androgens, Aplastic Anemia, Bone Marrow Failure Syndromes, Idiopathic Pulmonary Fibrosis, Telomere, Telomere Shortening
Medical subject headings
Anemia, Aplastic, Bone Marrow Failure Disorders, Idiopathic Pulmonary Fibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nandrolone DecanoateDrug

Study groups in NCT02055456
Study groupRoleWhat they receive
Nandrolone DecanoateExperimentalNandrolone Decanoate intramuscularly administered, every two weeks, 5 mg/kg/dose
Receives: Drug: Nandrolone Decanoate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Reduction in telomere attrition

    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

    Measured: 2 years

Secondary outcomes (5)

  1. Hematologic response

    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%

    Measured: 2 years

  2. Clonal evolution

    Number of participants that evolute to myelodysplasia or acute leukemia.

    Measured: 2 years

  3. Improvement in lung function

    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

    Measured: 2 years

  4. Survival

    Measured: 2 years

  5. Safety

    Number of participants with adverse effects attributed to the use of nandrolone decanoate during the 24 months treatment period.

    Measured: 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Feb 2014 (estimated)
  2. Study start1 Feb 2014
  3. Primary completion1 Feb 2017
  4. Study completion1 Feb 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02055456
Sponsor's protocol ID
11-H-RTC-0002
Status last verified
Aug 2023
First submitted
3 Feb 2014
Last updated
31 Aug 2023
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 16778145

  • 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.

    PubMed 18239083

  • 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.

    PubMed 15814878

  • 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.

    PubMed 19561322

  • Calado RT, Young NS. Telomere diseases. N Engl J Med. 2009 Dec 10;361(24):2353-65. doi: 10.1056/NEJMra0903373. No abstract available.

    PubMed 20007561

  • 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.

    PubMed 22476886

  • 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.

    PubMed 36579443

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Nandrolone Decanoate in people with Aplastic Anemia and Bone Marrow Failure Syndromes, run by University of Sao Paulo at 1 site in Brazil.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 31 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Reduction in telomere attrition (time frame: 2 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02055456, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2023.

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