A Pilot Study on Neuroimaging in SCD: Part of The Boston Consortium to Cure Sickle Cell Disease

Boston Children's Hospital

Status: Enrolling

Conditions: Sickle Cell Disease

Treatments: Device: MRI; Device: FDNIRS-DCS

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04166526

IRB-P00033322

1OT2HL152640-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Sickle Cell Disease (SCD) impairs oxygen transport to tissue and causes endothelial injury. Thus, therapeutic interventions aim to improve both, but there is an unmet need for biomarkers to determine when intervention is necessary and evaluate the effectiveness of the chosen intervention in individual patients. This study proposes to monitor SCD and its treatment through their impact on cerebral hemodynamics, as the brain is one of the most vulnerable and consequential targets of the disease. Specifically, this study will optimize quantitative magnetic resonance imaging (MRI) and advanced optical spectroscopy techniques such as frequency-domain near-infrared and diffuse correlation spectroscopies (FDNIRS-DCS) to monitor 1) cerebral oxygen transport with measures of cerebral blood flow (CBF), cerebral oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2) and 2) endothelial function with cerebrovascular reactivity (CVR).

Additionally, this study aims to monitor baseline cerebral oxygen transport and CVR, as well as changes that occur with treatment (transfusion or genetic therapy to induce fetal hemoglobin) and assess hemoglobinopathy patients with known genotypes and phenotypes. The ultimate goal is to demonstrate the potential of this monitoring approach to select individual SCD subjects for interventions and evaluate individual responses to treatment. Success will help justify inclusion of these modalities in ongoing and future clinical trials of novel SCD therapies.

Enrollment: 8 estimated patients

Sex: All

Ages: 8 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Group 1 (healthy controls):

• Children ages 8-18 without SCD

Group 2 (SCD patients without treatment):

• SCD patients ages 8-18 who:

  • have not undergone gene therapy or a bone marrow transplant
  • are not receiving chronic transfusions
  • have not received a blood transfusion in the past 3 months

Group 3 (SCD patients who have undergone gene therapy):

• SCD patients ages 8-18 who have had gene therapy at least one month prior to enrollment

Group 4 (SCD patients who have chronic transfusions):

• SCD patients ages 8-18 who receive chronic transfusions

Exclusion criteria

• Electrical implants such as cardiac pacemakers or perfusion pumps;
• Ferromagnetic implants such as aneurysm clips, surgical clips, prosthesis, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants;
• Ferromagnetic objects such as jewelry or metal clips;
• Women of childbearing age who are seeking to become pregnant, who are breastfeeding, or who suspect they may be pregnant;
• Pre-existing medical conditions including a likelihood of developing seizures or claustrophobic reactions;
• Any greater than normal potential for cardiac arrest;
• Subjects requiring sedation for MRI

Trial design

8 participants in 4 patient groups

Group 1: Typically developing children

Description:

Participants of this group will not have a diagnosis of SCD. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.

Treatment:

Device: FDNIRS-DCS

Device: MRI

Group 2: Children with SCD not receiving treatment

Description:

Participants of this group have a diagnosis of SCD, but do not receive chronic transfusions, gene therapy or bone marrow transplants. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.

Treatment:

Device: FDNIRS-DCS

Device: MRI

Group 3: Children with SCD who have undergone gene therapy

Description:

Participants of this group have a diagnosis of SCD and have had gene therapy at least one month prior to enrollment. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.

Treatment:

Device: FDNIRS-DCS

Device: MRI

Group 4: Children with SCD who have chronic transfusions

Description:

Participants of this group have a diagnosis of SCD and receive chronic transfusions. These participants will undergo an MRI, lasting approximately an hour, with simultaneous FDNIRS-DCS monitoring.

Treatment:

Device: FDNIRS-DCS

Device: MRI