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The Congenital Dyserythropoietic Anemia Registry (CDAR)

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ClinicalTrials.gov Identifier: NCT02964494
Recruitment Status : Recruiting
First Posted : November 16, 2016
Last Update Posted : February 12, 2021
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
The investigators propose the creation and maintenance of a comprehensive registry for patients with the diagnosis of Congenital Dyserythropoietic Anemia (CDA) in North America. The goal of this registry will be to collect long-term confidential data on patients with CDA in the US, Canada, and Mexico and create a bio-repository of de-identified patient blood and bone marrow specimens as a tool for the investigation of epidemiology, natural history, biology, and molecular pathogenetic mechanisms of CDA.

Condition or disease
Congenital Dyserythropoietic Anemia (CDA)

Detailed Description:

To establish and maintain a CDA registry (CDAR): a comprehensive registry of subjects with the diagnosis of any type of congenital dyserythropoietic anemia in North America. Subjects and their physicians have expressed interest in participating in a national/international registry that could promote research and further understanding of this rare disease-group.

CDAs consist a heterogeneous group of rare genetic disorders causing ineffective erythropoiesis with the characteristic finding of multinuclear erythroid precursors in the bone marrow. The other hematopoietic lineages seem unaffected. The diagnosis of CDA is clinically challenging and is based on identifying the characteristic morphology of erythroblasts in the bone marrow of subjects presenting with chronic anemia, frequently with evidence of hemolysis but suboptimal reticulocytosis, and iron overload. Three types are well-defined by marrow morphology, although a recent classification recognizes seven different genetic types. Since certain gene defects were identified in the different types of CDAs, our understanding of the biology and pathogenesis of these diseases has been improving. However, many gaps still exist in our understanding of the related molecular mechanisms primarily due to the rarity of the disease and the lack of systematic approach to study these subjects. In addition, the heterogeneity observed among subjects and the clinical overlap with other hematologic disorders, namely hemolytic anemias with brisk erythropoietic response that may be associated with erythroid dysplasia, and with ineffective erythropoiesis, further complicates the diagnosis and often delays appropriate diagnosis and therapy.

The purpose of CDAR will be to establish a database and bio-repository for CDA subjects and their families in order to systematically study this rare disease-group. Data regarding these subjects will be collected confidentially at initial presentation or diagnosis and periodically thereafter over a long period of time (>15 years). In addition, blood, bone marrow and/or DNA samples of enrolled subjects will be stored for research studies with the aim to improve our understanding, diagnosis, and treatment of CDA.

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Study Type : Observational [Patient Registry]
Estimated Enrollment : 10000 participants
Observational Model: Other
Time Perspective: Other
Target Follow-Up Duration: 15 Years
Official Title: The Congenital Dyserythropoietic Anemia Registry (CDAR)
Actual Study Start Date : August 29, 2016
Estimated Primary Completion Date : July 2026
Estimated Study Completion Date : January 2031





Primary Outcome Measures :
  1. Age and symptoms at presentation and/or diagnosis [ Time Frame: From study entry to >15 years ]
    Clinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  2. Degree of anemia [ Time Frame: From study entry to >15 years ]
    Clinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  3. Clinical course during [ Time Frame: From study entry to >15 years ]
    infancyClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  4. Growth and development, endocrinologic evaluation, skeletal [ Time Frame: From study entry to >15 years ]
    dysplasiasClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  5. Transfusion requirements [ Time Frame: From study entry to >15 years ]
    requirementsClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  6. Evidence and complications of hemolysis and of extramedullary [ Time Frame: From study entry to >15 years ]
    erythropoiesisClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  7. Iron overload, frequency and methods of monitoring, iron chelators, effectiveness and history of side effects if [ Time Frame: From study entry to >15 years ]
    usedClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  8. Splenomegaly, history of splenectomy and effect if performed; possible complications, e.g. thrombosis or [ Time Frame: From study entry to >15 years ]
    sepsisClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  9. History of stem cell transplant, effect, complications [ Time Frame: From study entry to >15 years ]
    Clinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  10. Other medications, e.g. interferon A for CDA-I, effect on anemia and on transfusion frequency, any side effects [ Time Frame: From study entry to >15 years ]
    notedClinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.

  11. Ethnic background and demographic information will also be collected for epidemiologic studies [ Time Frame: From study entry to >15 years ]
    Clinical and laboratory information will be collected by the patient and the referring physician with questionnaires in order to obtain the natural history of the disease, including correlations, epidemiology, and biology of the different types of CDA.


Biospecimen Retention:   Samples With DNA

Subject DNA isolated from subject's oral cells or blood or other biological samples donated to be used for gene sequencing diagnostic studies (evaluate for known or novel genes that may be causative of CDA)

Bone marrow will be collected ONLY when bone marrow samples are being collected for standard diagnostic or treatment related reasons. No interventional procedure other than a voluntary blood draw, if patient consents, is required as part of the CDAR Registry



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Congenital Dyserythropoietic Anemia (CDA)
Criteria

Inclusion Criteria:

  • Diagnosis of Congenital Dyserythropoietic Anemia (CDA), whether a genetic mutation is identified or not
  • Evidence of congenital anemia/jaundice or a positive family history
  • Evidence of ineffective erythropoiesis
  • Typical morphological appearance of bone marrow erythroblasts
  • All ages (ages 0-99)

Exclusion Criteria:

  • Diagnosis of cancer
  • Myelodysplasia
  • Secondary dyserythropoiesis: e.g.; vitamin B12 deficiency or drug-related.

Note1: Patients with rare band 3 (SLC4A1) mutations recently described to be associated with dyserythropoiesis will be eligible since the mechanisms appear to involve direct participation of band 3 in the erythroblast mitosis and cytokinesis.

Note2: Siblings, parents, and family members of patients with confirmed CDA diagnosis are encouraged to participate in the study.


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): NCT02964494


Contacts
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Contact: Hotline 513-636-6770

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Hotline    513-636-6770    theodosia.kalfa@cchmc.org   
Principal Investigator: Theodosia Kalfa, MD, PhD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Theodosia Kalfa, MD, PhD Children's Hospital Medical Center, Cincinnati
Additional Information:

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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02964494    
Other Study ID Numbers: 2016-2727_CDAR
First Posted: November 16, 2016    Key Record Dates
Last Update Posted: February 12, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Data regarding subjects that meet inclusion will be collected confidentially at initial presentation or diagnosis and periodically thereafter over a long period of time (>15 years). In addition, blood, bone marrow and/or DNA samples of enrolled subjects will be stored for research studies with the aim to improve diagnosis, treatment and care of CDA.

The samples and medical information (that is not associated with a patient's name) may be used by other researchers studying CDA, at Cincinnati Children's Hospital Medical Center or at other institutions. The researchers must get Institutional Review Board (a board that is in charge of regulating research done on people) approval prior to requesting data and/or samples from this repository if applicable. No identifying information (that associates the medical information with the subject or sample) will be available to them.


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia
Anemia, Dyserythropoietic, Congenital
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Genetic Diseases, Inborn