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Trial record 60 of 698 for:    Sickle Cell Disease

Novel Cardiac Magnetic Resonance Imaging to Define a Unique Restrictive Cardiomyopathy in Sickle Cell Disease

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ClinicalTrials.gov Identifier: NCT02410811
Recruitment Status : Completed
First Posted : April 8, 2015
Last Update Posted : June 18, 2019
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:
The purpose of this study is to use cardiac magnetic resonance imaging (CMR) and echocardiographic tissue Doppler imaging to demonstrate a unique restrictive cardiomyopathy of sickle cell disease. The investigators will characterize its frequency and how it might change (e.g., presence/absence and severity) over a 2-year period.

Condition or disease Intervention/treatment
Sickle Cell Disease Other: Cardiac magnetic resonance imaging (CMR)

Detailed Description:

Sickle cell disease (SCD) causes progressive cardiopulmonary morbidity, beginning in childhood, which can ultimately be fatal. As a group, cardiopulmonary complications, such as acute chest syndrome and sudden death, are now the most common causes of death in SCD, especially in adolescents and adults.

Patients with SCD have features of both an anemia-related, high cardiac output state and a restrictive cardiomyopathy (RCM). The investigators propose that this unique RCM is an overlooked and understudied complication of SCD. RCM could explain the modest increases in pulmonary artery pressure in patients with SCD, as measured by cardiac catheterization or estimated by tricuspid regurgitant jet velocity (TRJV), which has often been attributed to a primary pulmonary arterial hypertension (PAH). RCM could also be the cause of unexplained sudden cardiac death in SCD, which is a feature of other forms of RCM.

The investigators overarching hypothesis is that increased reactive oxygen species (ROS)-mediated angiotensin-1 receptor (AT1R)-TGFβ1 signaling is pro-fibrotic and, in combination with vaso-occlusive ischemia-reperfusion injury, results in an age-dependent, progressive RCM that can be detected by non-invasive cardiac imaging.

This pilot, longitudinal, observational study uses a novel, comprehensive, multimodal cardiac imaging strategy, combining cutting-edge cardiac magnetic resonance imaging (CMR) and echocardiographic tissue Doppler imaging (TDI), to demonstrate the unique RCM of SCD, characterizing its frequency and the temporal evolution over a 2-year period. The investigators will also correlate the RCM phenotype with biomarkers of ROS and renin angiotensin system (RAS)-TGFβ1 signaling.

This research could change the investigators understanding of how SCD affects the heart and lungs. The investigators propose studies that will change the current concept of primary pulmonary vasculopathy to a cardiomyopathy-centered model with secondary pulmonary vascular changes leading to sudden death. This translational pilot study will deliver a novel, clear, quantifiable CMR phenotype with established diagnostic performance that will be used in phase II/III clinical trials to test anti-fibrotic therapy to prevent or reverse SCD-related RCM.


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Study Type : Observational
Actual Enrollment : 32 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Novel Cardiac Magnetic Resonance Imaging to Define a Unique Restrictive Cardiomyopathy in Sickle Cell Disease
Study Start Date : January 31, 2014
Actual Primary Completion Date : January 29, 2018
Actual Study Completion Date : May 20, 2019


Group/Cohort Intervention/treatment
Age Stratum A
  • Age 6 to 13.99 years
  • Cardiac magnetic resonance imaging (CMR)
Other: Cardiac magnetic resonance imaging (CMR)
CMR is obtained on all participants in all arms/groups

Age Stratum B
  • Age 14 to 20.99 years
  • Detectible and quantifiable TRJV with reported value
  • Cardiac magnetic resonance imaging (CMR)
Other: Cardiac magnetic resonance imaging (CMR)
CMR is obtained on all participants in all arms/groups

Age Stratum C
  • Age ≥21 years
  • Detectible and quantifiable TRJV with reported value
  • Cardiac magnetic resonance imaging (CMR)
Other: Cardiac magnetic resonance imaging (CMR)
CMR is obtained on all participants in all arms/groups

Age Stratum D
  • Age ≥6 years.
  • Current use of disease-modifying therapy [hydroxyurea, chronic transfusions, or both (given concurrently, sequentially, or both)] that was initiated at <3 years of age, and for which there has been no interruption of therapy for >6 consecutive months since the initiation of disease-modifying therapy.
  • Cardiac magnetic resonance imaging (CMR)
Other: Cardiac magnetic resonance imaging (CMR)
CMR is obtained on all participants in all arms/groups




Primary Outcome Measures :
  1. Frequency of RCM Phenotype [ Time Frame: 3 years ]

Other Outcome Measures:
  1. Stability of RCM phenotype as indicated by frequency of change in classification of RCM phenotype [presence or absence] over time [ Time Frame: 3 years ]

Biospecimen Retention:   Samples With DNA

Participants will have to give blood and urine.

Visit 1:

Sample of blood (about 2 tablespoons) for:

  • routine lab tests to check the health of the heart and the extent of participants sickle cell disease
  • research lab tests to check for biomarkers (substances found in blood that are signs of a disease, condition or normal/abnormal process) of heart problems, blood clotting activity and to extract DNA for genetic testing
  • 1 tablespoon of urine for routine tests to check health

Visit 2 (1 year after 1st visit):

  • Sample of blood (about 2 tablespoons) for routine and research lab tests
  • 1 tablespoon of urine for routine tests to check health

    24-Hour Urine Sample (after Visits 1, 2, and 3):

  • Participants will be asked to collect and return a 24 hour urine sample after visits 1, 2, and 3.


Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Enrolling a maximum of 40 participants in the entire study across four age strata: A, 6 - 13.9 years; B, 14 - 20.9 years; C, 21 years and older; and D, 6 years and older.
Criteria

Inclusion Criteria:

  • Sickle cell anemia (HbSS) or sickle-β°-thalassemia (HbSβ°) confirmed by hemoglobin separation and identification techniques
  • Ability to cooperate with and undergo CMR without sedation or anesthesia.
  • Ability to cooperate with and undergo echocardiogram
  • Written informed consent in accordance with the institutional policies and federal guidelines must be provided by the participant (if ≥18 years of age) or parent or legally authorized guardian (if the participant is <18 years of age) Minor participants ≥11 years of age will be requested to provide assent

The following additional inclusion criterion applies to Age Stratum A:

Age 6 to 13.99 years

The following additional inclusion criteria apply to Age Stratum B:

  • Age 14 to 20.99 years
  • Detectible and quantifiable TRJV with reported value

The following additional inclusion criteria apply to Age Stratum C:

  • Age ≥21 years
  • Detectible and quantifiable TRJV with reported value

The following additional inclusion criteria apply to Stratum D:

  • Age ≥6 years.
  • Current use of disease-modifying therapy [hydroxyurea, chronic transfusions, or both (given concurrently, sequentially, or both)] that was initiated at <3 years of age, and for which there has been no interruption of therapy for >6 consecutive months since the initiation of disease-modifying therapy.

Exclusion Criteria:

  • Any contraindication to MRI or physical or behavioral factor that could degrade the quality of MRI data or interfere with a participant's tolerance of the MRI, such as permanent or semi-permanent metallic implants, including pacemakers and defibrillators, or severe claustrophobia
  • Known ventricular septal defect (VSD) documented in medical record
  • Estimated Glomerular Filtration Rate (eGFR) <60 mL/min/1.73 m2 (estimated by serum creatinine or cystatin-C)
  • Pregnancy (documented by serum or urine pregnancy test)

The following additional inclusion criterion applies to strata A, B and C only:

- Current chronic transfusion therapy (defined as regular, approximately monthly, transfusions of packed red blood cells given for at least 6 consecutive months for the treatment of prevention of SCD-related complications with the plan to continue this therapy at the time of potential enrollment).


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): NCT02410811


Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Charles T Quinn, M.D. Children's Hospital Medical Center, Cincinnati
Principal Investigator: Michael D Taylor, MD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Robert J Fleck, M.D. Children's Hospital Medical Center, Cincinnati
Principal Investigator: Omar Y Niss, M.D. Children's Hospital Medical Center, Cincinnati

Publications of Results:
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT02410811     History of Changes
Other Study ID Numbers: 2012-4851
First Posted: April 8, 2015    Key Record Dates
Last Update Posted: June 18, 2019
Last Verified: June 2019
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Sickle Cell Disease (SCD)
Cardiac Magnetic Resonance Imaging (CMR)
Cardiomyopathy
Pulmonary Hypertension
Additional relevant MeSH terms:
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Anemia, Sickle Cell
Heart Diseases
Cardiovascular Diseases
Hematologic Diseases
Genetic Diseases, Inborn
Cardiomyopathies
Cardiomyopathy, Restrictive
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hemoglobinopathies