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

NCT02410811 | Completed Results

• 1 other identifier: 2012-4851
• Study Type: observational
• Target: 33
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Disease (SCD); Cardiac Magnetic Resonance Imaging (CMR); Cardiomyopathy; Pulmonary Hypertension

Outcome Measures

Primary Outcomes (1)

• Frequency of the Diffuse Myocardial Fibrosis Phenotype

  The occurrence of an abnormally increased extracellular volume (ECV) measurement \[i.e., the presence of the diffuse myocardial fibrosis phenotype\] as assessed by cardiac magnetic resonance imaging (CMR) using T1 mapping before and after administration of gadolinium. Expressed as number of participants with the diffuse myocardial fibrosis phenotype in each stratum.

  Assessed annually over a 2-year period (3 assessments over 2 years)

Other Outcomes (1)

• Stability of the Diffuse Myocardial Fibrosis Phenotype Over Time

  Assessed annually over a 2-year period (3 assessments over 2 years)

Study Arms (4)

Age Stratum A

* Age 6 to 13.99 years * Cardiac magnetic resonance imaging (CMR)

Other: Cardiac magnetic resonance imaging (CMR)

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)

Age Stratum C

* Age ≥21 years * Detectible and quantifiable TRJV with reported value * Cardiac magnetic resonance imaging (CMR)

Other: Cardiac magnetic resonance imaging (CMR)

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)

Interventions

Cardiac magnetic resonance imaging (CMR) OTHER

CMR is obtained on all participants in all arms/groups

Age Stratum A; Age Stratum B; Age Stratum C; Age Stratum D

Eligibility Criteria

• Age: 6 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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
• Age 6 to 13.99 years
• Age 14 to 20.99 years
• Detectible and quantifiable TRJV with reported value
• Age ≥21 years
• Detectible and quantifiable TRJV with reported value
• 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.

You may not qualify if:

• 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)
• \- 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).

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (5)

• Powell AW, Alsaied T, Niss O, Fleck RJ, Malik P, Quinn CT, Mays WA, Taylor MD, Chin C. Abnormal submaximal cardiopulmonary exercise parameters predict impaired peak exercise performance in sickle cell anemia patients. Pediatr Blood Cancer. 2019 Jun;66(6):e27703. doi: 10.1002/pbc.27703. Epub 2019 Mar 7.

  PMID: 30848046 RESULT

• Alsaied T, Niss O, Powell AW, Fleck RJ, Cnota JF, Chin C, Malik P, Quinn CT, Taylor MD. Diastolic dysfunction is associated with exercise impairment in patients with sickle cell anemia. Pediatr Blood Cancer. 2018 Aug;65(8):e27113. doi: 10.1002/pbc.27113. Epub 2018 May 21.

  PMID: 29781568 RESULT

• Niss O, Fleck R, Makue F, Alsaied T, Desai P, Towbin JA, Malik P, Taylor MD, Quinn CT. Association between diffuse myocardial fibrosis and diastolic dysfunction in sickle cell anemia. Blood. 2017 Jul 13;130(2):205-213. doi: 10.1182/blood-2017-02-767624. Epub 2017 May 15.

  PMID: 28507082 RESULT

• Niss O, Quinn CT, Lane A, Daily J, Khoury PR, Bakeer N, Kimball TR, Towbin JA, Malik P, Taylor MD. Cardiomyopathy With Restrictive Physiology in Sickle Cell Disease. JACC Cardiovasc Imaging. 2016 Mar;9(3):243-52. doi: 10.1016/j.jcmg.2015.05.013. Epub 2016 Feb 17.

  PMID: 26897687 RESULT

• Niss O, Morin CE, Hashemi S, Alsaied T, Lang SM, Taylor MD, Tasset M, Malik P, Quinn CT. Longitudinal changes and predictors of cardiac extracellular volume fraction in sickle cell anemia. Blood Red Cells Iron. 2025 Dec;1(3):100031. doi: 10.1016/j.brci.2025.100031. Epub 2025 Nov 20.

  PMID: 41312339 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Blood, DNA, and urine specimens.

MeSH Terms

Conditions

Anemia, Sickle Cell; Cardiomyopathies; Hypertension, Pulmonary

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heart Diseases; Cardiovascular Diseases; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases

Limitations and Caveats

All participants in strata A, B and C had severe diffuse myocardial fibrosis. That is, all participants had the phenotype for which we assessed, so correlative studies (e.g., affected vs. non-affected) could not be performed. Therefore, we amended the protocol and opened an additional, fourth stratum (D) to study individuals who were previously not eligible for inclusion.

Results Point of Contact

• Title: Dr. Charles T. Quinn
• Organization: Cincinnati Children's Hospital Medical Center

charles.quinn@cchmc.org

5138033086

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2014
• First Posted: April 8, 2015
• Study Start: January 31, 2014
• Primary Completion: January 29, 2018
• Study Completion: May 20, 2019
• Last Updated: November 2, 2020
• Results First Posted: November 2, 2020

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)