Sickle Cell DiseaseNCT02410811

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

An observational study of Sickle Cell Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 6 to 65 years
Conditions the study is for: Sickle Cell Disease
What is being tested?: Cardiac magnetic resonance imaging (CMR)
How many people: 33 participants
Where: 1 siteUnited States
Study dates: 31 Jan 2014to 20 May 2019
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 6 to 65 years
All sexes
No healthy volunteers
Child, Adult, Older adult

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.

Who may be able to join

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

Show all 15Show fewer

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.

Who cannot join

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).

Trial locations and contacts

1 site in 1 country.

United States1 site

Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229

Other trials in United States

About this study

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.

Read the 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.

Conditions: Sickle Cell Disease
Being tested: Cardiac magnetic resonance imaging (CMR)
Keywords: Sickle Cell Disease (SCD), Cardiac Magnetic Resonance Imaging (CMR), Cardiomyopathy, Pulmonary Hypertension
Medical subject headings: Anemia, Sickle Cell, Cardiomyopathies, Hypertension, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Cardiac magnetic resonance imaging (CMR)Other
CMR is obtained on all participants in all arms/groups

Study groups in NCT02410811
Study group	Role	What they receive
Age Stratum A		* Age 6 to 13.99 years * Cardiac magnetic resonance imaging (CMR) Receives: 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) Receives: Other: Cardiac magnetic resonance imaging (CMR)
Age Stratum C		* Age ≥21 years * Detectible and quantifiable TRJV with reported value * Cardiac magnetic resonance imaging (CMR) Receives: 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) Receives: Other: Cardiac magnetic resonance imaging (CMR)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jan 201420 May 2019

First posted8 Apr 2015 (estimated)
Study start31 Jan 2014
Primary completion29 Jan 2018
Study completion20 May 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
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: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 33 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02410811
Sponsor's protocol ID: 2012-4851
Status last verified: Jun 2019
First submitted: 2 May 2014
Last updated: 2 Nov 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Publications

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.
PubMed 30848046
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.
PubMed 29781568
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.
PubMed 28507082
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.
PubMed 26897687
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.
PubMed 41312339

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

All Sickle Cell Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 2 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Novel Cardiac Magnetic Resonance Imaging to Define a Unique Restrictive Cardiomyopathy in Sickle Cell Disease
ClinicalTrials.gov ID: NCT02410811
Acronym / sponsor ID: 2012-4851
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Disease (SCD), Cardiac Magnetic Resonance Imaging (CMR), Cardiomyopathy, Pulmonary Hypertension
Study type: Observational
Recruitment status: Completed
Enrolment: 33 participants (actual)
Lead sponsor: Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
Study start: 31 Jan 2014
Primary completion: 29 Jan 2018 (actual)
Study completion: 20 May 2019 (actual)
First posted: 8 Apr 2015 (estimated)
Results: Posted 2 Nov 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 4

Arm	Type	Receives
Age Stratum A	–	Other: Cardiac magnetic resonance imaging (CMR)* Age 6 to 13.99 years * Cardiac magnetic resonance imaging (CMR)
Age Stratum B	–	Other: Cardiac magnetic resonance imaging (CMR)* Age 14 to 20.99 years * Detectible and quantifiable TRJV with reported value * Cardiac magnetic resonance imaging (CMR)
Age Stratum C	–	Other: Cardiac magnetic resonance imaging (CMR)* Age ≥21 years * Detectible and quantifiable TRJV with reported value * Cardiac magnetic resonance imaging (CMR)
Age Stratum D	–	Other: Cardiac magnetic resonance imaging (CMR)* 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)

Who may qualify

Ages: 6 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult
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.

Key inclusion criteria (15 listed)

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

Key exclusion criteria (6 listed)

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).

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
Cardiac magnetic resonance imaging (CMR)CMR is obtained on all participants in all arms/groups	Other	Age Stratum A, Age Stratum B, Age Stratum C, Age Stratum D

Primary outcome

Frequency of the Diffuse Myocardial Fibrosis Phenotype
Time frame: Assessed annually over a 2-year period (3 assessments over 2 years)
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.

Results and safety

Results posted to the registry on 2 Nov 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Stratum A (6-13.99 Years)	5	5
Stratum B (14-20.99 Years)	10	10
Stratum C (≥21 Years)	11	10
Stratum D (Early Treatment)	7	7

Primary outcome: Frequency of the Diffuse Myocardial Fibrosis Phenotype

Time frame: Assessed annually over a 2-year period (3 assessments over 2 years). Count of participants. Unit: Participants

Measure	Stratum A (6-13.99 Years) n = 5	Stratum B (14-20.99 Years) n = 10	Stratum C (≥21 Years) n = 10	Stratum D (Early Treatment) n = 7
Value	5	10	10	1

Adverse events

Time frame: AEs were collected for three, separate 30-day intervals over the entire study period of 2 years. Each 30-day interval was defined as starting with the study visit during which annual study activities were performed (e.g., cardiac magnetic resonance imaging [CMR]) and ending 30 days after that study visit. AEs were assessed as they occurred during each study visit, and AEs that occurred in the 30 days after each study visit were collected by scripted phone call from the study team.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Stratum A (6-13.99 Years)	0 of 5 (0%)	0 of 5 (0%)	0 of 5
Stratum B (14-20.99 Years)	0 of 10 (0%)	3 of 10 (30%)	0 of 10
Stratum C (≥21 Years)	0 of 10 (0%)	1 of 10 (10%)	0 of 10
Stratum D (Early Treatment)	0 of 7 (0%)	0 of 7 (0%)	0 of 7

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 30848046Powell 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.
Results publication: PubMed 29781568Alsaied 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.
Results publication: PubMed 28507082Niss 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.
Results publication: PubMed 26897687Niss 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.
Derived from this study: PubMed 41312339Niss 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.
Individual participant dataSharing planned: No

Related trials for Sickle Cell Disease

Active, not recruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis

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.

Charles T Quinn, M.D. principal investigator

Children's Hospital Medical Center, Cincinnati

Michael D Taylor, MD principal investigator

Children's Hospital Medical Center, Cincinnati

Robert J Fleck, M.D. principal investigator

Children's Hospital Medical Center, Cincinnati

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Sickle Cell Disease, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

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 15 inclusion and 6 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: finished, as of the sponsor's last update on 2 Nov 2020. 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 United States. 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.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency of the Diffuse Myocardial Fibrosis Phenotype (time frame: Assessed annually over a 2-year period (3 assessments over 2 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02410811, which also lists 5 linked publications.

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 2 Nov 2020.