Diamond Blackfan AnemiaPhase 2NCT02386267
L-leucine in Diamond Blackfan Anemia Patients
A Phase 2 study testing L-leucine in people with Diamond Blackfan Anemia, run by Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache at 1 site in Russia.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 year to 20 years
- Conditions the study is for
- Diamond Blackfan Anemia
- What is being tested?
- L-leucine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteRussia
- Study dates
- Sep 2014to Mar 2016
- Phase
- Phase 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 1 year to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- signed Informed Consent Form
- diagnosed Diamond Blackfan Anemia
- transfusion dependenсe
- adequate renal function
- adequate liver function
- negative B-HCG and adequate contraception
Who cannot join
- known hypersensitivity to branched chain amino acids
- diagnosed AA metabolism disorder
- prior HSCT
- pregnancy or planning to become pregnant
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Federal Scientific Clinical Centre of Pediatric Hematology Oncology Immunology n.a. Dmitry Rogachev
Moscow, 117997
Natalia - SMETANINA, MD, PhD, +7 985 647 13 05 ext. 13 05, Nataliya.smetanina@fccho-moscow.ru
About this study
Official title: Therapeutic Use of the Amino Acid Leucine in the Treatment of Transfusion-Dependent Diamond Blackfan Anemia Patients
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.
Read more
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.
Read the detailed description
Experimental: one arm L-leucine , dose- 700mg/m2 , per os, 3 time a day, 6 months
- Conditions
- Diamond Blackfan Anemia
- Being tested
- L-leucine
- Medical subject headings
- Anemia, Diamond-Blackfan
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-leucineDrug
L-leucine pills per os for 6 months
| Study group | Role | What they receive |
|---|---|---|
| L-leucine pills | Experimental | L-leucine , dose- 700mg/m2 , per os, three time a day, course duration 6 months Receives: Drug: L-leucine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hemoglobin level
Response to the treatment can be one of the following:
- Complete response (CR): Hb > 9 gm/dL and transfusion-independence as defined in DBA
- Partial response (PR): Hb < 9 gm/dL, increased reticulocyte count > 1% and any increase in transfusion interval from baseline.
- No response (NR): no change in transfusion requirements and no significant change in Hb or reticulocytes
- Progression: worsening of disease as defined by the need for more frequent transfusions
Measured: every 4 weeks for 12 months
Secondary outcomes (1)
Side effects of L-leucine in transfusion-dependent DBA patients for one year
Measured: every 4 weeks for 12 moths
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2015 (estimated)
- Study startSep 2014
- Primary completionMar 2015 (estimated)
- Study completionMar 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Diamond Blackfan AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Natalia - SMETANINA, MD, PhD, Principal investigator, FSCCPHOI, Outpatient Department
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02386267
- Sponsor's protocol ID
- Ru0001
- Status last verified
- Mar 2015
- First submitted
- 18 Feb 2015
- Last updated
- 11 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Use of the Amino Acid Leucine in the Treatment of Transfusion-Dependent Diamond Blackfan Anemia Patients
- ClinicalTrials.gov ID
- NCT02386267
- Acronym / sponsor ID
- Ru0001
- Conditions
- Diamond Blackfan Anemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry RogacheUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Mar 2015 (estimated)
- Study completion
- Mar 2016 (estimated)
- First posted
- 11 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Experimental: one arm L-leucine , dose- 700mg/m2 , per os, 3 time a day, 6 months
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L-leucine pills | Experimental | Drug: L-leucineL-leucine , dose- 700mg/m2 , per os, three time a day, course duration 6 months |
Who may qualify
- Ages
- 1 year to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- signed Informed Consent Form
- diagnosed Diamond Blackfan Anemia
- transfusion dependenсe
- adequate renal function
- adequate liver function
Key exclusion criteria (4 listed)
- known hypersensitivity to branched chain amino acids
- diagnosed AA metabolism disorder
- prior HSCT
- pregnancy or planning to become pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-leucineL-leucine pills per os for 6 months | Drug | L-leucine pills |
Primary outcome
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
1 secondary outcome
Side effects of L-leucine in transfusion-dependent DBA patients for one year
Time frame: every 4 weeks for 12 moths
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalia - SMETANINA, MD, PhD principal investigator
FSCCPHOI, Outpatient Department
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-leucine in people with Diamond Blackfan Anemia, run by Federal Scientific Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitry Rogache at 1 site in Russia.
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 6 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: status not confirmed, as of the sponsor's last update on 11 Mar 2015. 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 Russia. 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 phase mean?
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Natalia - SMETANINA, MD, PhD (+7 985 647 13 05 ext. 13 05, Nataliya.Smetanina@fccho-moscow.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hemoglobin level (time frame: every 4 weeks for 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 11 Mar 2015.