NCT02055456

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2014

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

February 3, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 5, 2014

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2017

Completed
Last Updated

August 31, 2023

Status Verified

August 1, 2023

Enrollment Period

3 years

First QC Date

February 3, 2014

Last Update Submit

August 28, 2023

Conditions

Aplastic AnemiaBone Marrow Failure SyndromesIdiopathic Pulmonary FibrosisTelomere Shortening

Keywords

HormonesAndrogensAplastic AnemiaBone Marrow Failure SyndromesIdiopathic Pulmonary FibrosisTelomereTelomere Shortening

Outcome Measures

Primary Outcomes (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

    2 years

Secondary Outcomes (5)

  • Hematologic response

    2 years

  • Clonal evolution

    2 years

  • Improvement in lung function

    2 years

  • Survival

    2 years

  • Safety

    2 years

Study Arms (1)

Nandrolone Decanoate

EXPERIMENTAL

Nandrolone Decanoate intramuscularly administered, every two weeks, 5 mg/kg/dose

Drug: Nandrolone Decanoate

Interventions

Nandrolone DecanoateDRUG
Nandrolone Decanoate

Eligibility Criteria

Age2 Years - 99 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Ribeirao Preto School of Medicine, University of Sao Paulo

Ribeirão Preto, São Paulo, 14048-900, Brazil

Location

Related Publications (7)

  • 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: 16778145BACKGROUND

  • 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: 18239083BACKGROUND

  • 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: 15814878BACKGROUND

  • 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: 19561322BACKGROUND

  • 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: 20007561BACKGROUND

  • 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: 22476886BACKGROUND

  • 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.

    PMID: 36579443DERIVED

MeSH Terms

Conditions

Anemia, AplasticBone Marrow Failure DisordersIdiopathic Pulmonary Fibrosis

Interventions

Nandrolone Decanoate

Condition Hierarchy (Ancestors)

AnemiaHematologic DiseasesHemic and Lymphatic DiseasesBone Marrow DiseasesPulmonary FibrosisLung Diseases, InterstitialLung DiseasesRespiratory Tract Diseases

Intervention Hierarchy (Ancestors)

NandroloneEstrenesEstranesSteroidsFused-Ring CompoundsPolycyclic CompoundsTestosterone CongenersGonadal Steroid HormonesGonadal HormonesHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Rodrigo T Calado, MD, PhD

    Ribeirao Preto School of Medicine at University of Sao Paulo

    STUDY CHAIR

  • 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

    PRINCIPAL INVESTIGATOR

  • José Antonio Baddini Martinez, MD, PhD

    Ribeirao Preto School of Medicine at University of Sao Paulo

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
MD

Study Record Dates

First Submitted

February 3, 2014

First Posted

February 5, 2014

Study Start

February 1, 2014

Primary Completion

February 1, 2017

Study Completion

February 1, 2017

Last Updated

August 31, 2023

Record last verified: 2023-08

Locations

BR(1)