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L-leucine in Diamond Blackfan Anemia Patients

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ClinicalTrials.gov Identifier: NCT02386267
Recruitment Status : Unknown
Verified March 2015 by Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache.
Recruitment status was:  Recruiting
First Posted : March 11, 2015
Last Update Posted : March 11, 2015
Sponsor:
Information provided by (Responsible Party):
Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache

Brief Summary:

Diamond-Blackfan anemia (DBA) is a rare congenital syndrome associated with physical anomalies, short stature, red cell aplasia, and an increased risk of malignancy.

Mutations affecting genes encoding ribosomal proteins cause DBA. Genetic studies have identified heterozygous mutations in at least one of eight ribosomal protein genes in up to 50% of cases.

25% of patients carry a mutation in the ribosomal protein (RP)S19 gene, whereas mutations in RPS24, RPS17, RPL35A, RPL11, and RPL5 are rare.

p53 activation has been identified as a key component in the pathophysiology of DBA after cellular and molecular studies. Other potential mechanisms that warrant further investigation include impaired translation as the result of ribosomal insufficiency, which may be ameliorated by Leucine supplementation.

Despite significant improvements in understanding of the pathophysiology of Diamond Blackfan anemia (DBA), there have been few advances in therapy. The cornerstones of treatment remain corticosteroids,chronic red blood cell transfusions, and hematopoietic stem cell transplantation, each of which is fraught with complications. Other treatments have been shown to be effective in only a few patients or in individual case reports : IL-3, cyclosporine (alone or in combination with steroids), metaclopramide. Gene therapy is still a part of research programs.

There are some indications that the Amino Acid (AA) L-leucine, a translation enhancer, may have some efficacy in DBA and 5q-syndrome, which has the same altered ribosome functions as the DBA. L-leucine is an essential AA that is unique among the branched-chain AA acting as a nutrient regulator of protein synthesis in skeletal muscle and adipose tissue.

Several preclinical studies with DBA lymphocytes exposed to various L-leucine doses, have demonstrated that protein synthesis can be increased by using high doses L-leucine.

Recent clinical data on L-leucine therapeutic use have demonstrated increase the hemoglobin level and transfusion independence in patients with DBA and 5q-syndrom.

These data support the rationale for clinical trial on L-leucine use as a therapeutic agent for DBA patients.


Condition or disease Intervention/treatment Phase
Diamond Blackfan Anemia Drug: L-leucine Phase 2

Detailed Description:
Experimental: one arm L-leucine , dose- 700mg/m2 , per os, 3 time a day, 6 months

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Use of the Amino Acid Leucine in the Treatment of Transfusion-Dependent Diamond Blackfan Anemia Patients
Study Start Date : September 2014
Estimated Primary Completion Date : March 2015
Estimated Study Completion Date : March 2016


Arm Intervention/treatment
Experimental: L-leucine pills
L-leucine , dose- 700mg/m2 , per os, three time a day, course duration 6 months
Drug: L-leucine
L-leucine pills per os for 6 months




Primary Outcome Measures :
  1. Hemoglobin level [ Time Frame: every 4 weeks for 12 months ]

    Response to the treatment can be one of the following:

    1. Complete response (CR): Hb > 9 gm/dL and transfusion-independence as defined in DBA
    2. Partial response (PR): Hb < 9 gm/dL, increased reticulocyte count > 1% and any increase in transfusion interval from baseline.
    3. No response (NR): no change in transfusion requirements and no significant change in Hb or reticulocytes
    4. Progression: worsening of disease as defined by the need for more frequent transfusions


Secondary Outcome Measures :
  1. Side effects of L-leucine in transfusion-dependent DBA patients for one year [ Time Frame: every 4 weeks for 12 moths ]


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Ages Eligible for Study:   1 Year to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • signed Informed Consent Form
  • diagnosed Diamond Blackfan Anemia
  • transfusion dependenсe
  • adequate renal function
  • adequate liver function
  • negative B-HCG and adequate contraception

Exclusion Criteria:

  • known hypersensitivity to branched chain amino acids
  • diagnosed AA metabolism disorder
  • prior HSCT
  • pregnancy or planning to become pregnant

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): NCT02386267


Contacts
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Contact: Natalia - SMETANINA, MD, PhD +7 985 647 13 05 ext 13 05 Nataliya.Smetanina@fccho-moscow.ru
Contact: Galina - OVSYANNIKOVA, PhD +7 916 238 13 57 ext 1710 galina.ovsyannikova@fccho-moscow.ru

Locations
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Russian Federation
Federal Scientific Clinical Centre of Pediatric Hematology Oncology Immunology n.a. Dmitry Rogachev Recruiting
Moscow, Russian Federation, 117997
Contact: Natalia - SMETANINA, MD, PhD    +7 985 647 13 05 ext 13 05    Nataliya.smetanina@fccho-moscow.ru   
Sponsors and Collaborators
Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache
Investigators
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Principal Investigator: Natalia - SMETANINA, MD, PhD FSCCPHOI, Outpatient Department

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Responsible Party: Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache
ClinicalTrials.gov Identifier: NCT02386267     History of Changes
Other Study ID Numbers: Ru0001
First Posted: March 11, 2015    Key Record Dates
Last Update Posted: March 11, 2015
Last Verified: March 2015

Additional relevant MeSH terms:
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Anemia
Anemia, Diamond-Blackfan
Hematologic Diseases
Anemia, Hypoplastic, Congenital
Anemia, Aplastic
Red-Cell Aplasia, Pure
Bone Marrow Diseases
Genetic Diseases, Inborn