Exploring Near Infrared Spectroscopy (NIRS) Technologies for Assessment of Muscle Physiology, Tissue Oxygenation, and Blood Flow in Patients With Sickle Cell Disease (SCD)

Sickle cell disease (SCD) is an inherited disorder of the blood. SCD can injure the smallest blood vessels, which can cause pain and damage organs all over the body. Some treatments are available, but researchers need better ways to monitor the effects of these treatments. An imaging technique called near infrared spectroscopy (NIRS) may be helpful.

Objective:

To test NIRS as a tool for measuring oxygen levels, blood flow, and the makeup of skin and muscle in patients with SCD.

Eligibility:

People aged 18 years and older with SCD. Healthy volunteers are also needed as a comparison for the changes in SCD patients.

Design:

Participants will be screened. They will have a physical exam, and 1 teaspoon of blood will be drawn.

Participants will have NIRS testing on their second visit. Probes will be placed on their skin. A blood pressure cuff will be placed on their arm. The cuff will be filled with air for up to 5 minutes and then released. Participants may be asked to breathe at a certain rate or hold their breath during these measurements.

At this visit, participants will also have an ultrasound exam to get images of their heart. They will be monitored while they walk for 6 minutes. They will have 1 tablespoon of blood drawn. Their height, weight, and vital signs will be measured.

Participants may be asked to return for up to 4 additional visits for NIRS testing within 120 days, but this is optional. The visits must be at least 3 days apart. Each visit will last up to an hour....

Study Overview

• Status: Recruiting
• Conditions: SCD
• Intervention / Treatment: Diagnostic test: Non-Invasive Infrared Spectroscopy

Detailed Description

Study Description:

This is a non-interventional protocol to explore the role of near infrared spectroscopy (NIRS) technologies as a monitoring tool for assessment of peripheral tissue dynamics in patients with sickle cell disease (SCD). The study will be performed in the outpatient setting. Ethnically-matched healthy subjects will be recruited to participate in baseline NIRS assessments and serve as controls. It is hypothesized that quantitative NIRS will be sensitive to differences in hemodynamic responses between SCD patients and healthy controls in the setting of endothelial dysfunction. In parallel, routine methods of assessing cardiovascular health, including the six-minute walk test, transthoracic echocardiography, and cardiac biomarkers such as pro BNP will be acquired. NIRS holds tremendous potential as a novel point of care test in patients with SCD and may provide further insight on the natural history of the disease and allow for individualized clinical management.

A subset of up to 10 participants in each cohort (SCD patients as well as healthy AA subjects) may be invited to return to the Clinical Center for clinical and NIRS reassessment periodically for a maximum of 4 additional visits, at least 3 days apart, within a 120- day period from their initial (baseline) visit to test repeatability of the NIRS measurements.

Objectives:

Primary Objective:

To quantify baseline hemodynamics in SCD subjects at steady state utilizing NIRS and compare against established clinical/biomarker outcomes, including the six-minute walk test, transthoracic echocardiogram and pro BNP levels.

Secondary Objective:

To compare NIRS measurements in SCD subjects at steady state with NIRS measurements in healthy controls.

Tertiary Objective:

To quantify baseline hemodynamics in ethnically-matched healthy control subjects (HbAA) utilizing NIRS and compare against established clinical/biomarker outcomes, including the six-minute walk test, transthoracic echocardiogram and pro BNP levels.

Endpoints:

Primary Endpoints:

NIRS measurements that characterize tissue composition, tissue metabolism, and blood flow will be collected in SCD subjects in steady state. Primary endpoints include:

• Oxy-/deoxy- hemoglobin concentration for assessing tissue composition
• Tissue oxygen saturation for assessing tissue metabolism
• Blood flow index: Post-occlusion hyperemic response for describing endothelial function.

We will examine correlations between these endpoints and biomarker and clinical endpoints among SCD participants to assess the extent to which NIRS measurements may capture clinical features of SCD.

Secondary Endpoints:

The same endpoints described above will be collected from healthy controls and used to assess differences in tissue composition, tissue metabolism, blood flow between SCD subjects and controls.

Tertiary Endpoints:

To evaluate the tertiary objective of characterizing NIRS responses in healthy controls we will collect:

• Oxy-/deoxy- hemoglobin concentration for assessing tissue composition
• Tissue oxygen saturation for assessing tissue metabolism
• Blood flow index: Post-occlusion hyperemic response for describing endothelial function.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dianna Lovins; Phone Number: (301) 480-3765; Email: dianna.lovins@nih.gov
• Study Contact Backup: Name: Swee Lay Thein, M.D.; Phone Number: (301) 435-2345; Email: sweelay.thein@nih.gov

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • Recruiting
      • National Institutes of Health Clinical Center
      • Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR); Phone Number: TTY dial 711 800-411-1222; Email: ccopr@nih.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:

Sickle Cell Disease

• Individuals with confirmed sickle cell disease (HbSS and S beta 0 genotypes)
• 18 years of age and older
• Willingness and capacity to provide informed consent
• Individuals must be on stable does of Hydroxyurea for 90 days prior to baseline visit

Ethnically matched controls

• Individuals with HbAA genotype
• 18 years of age and older
• Willingness and capacity to provide informed consent

EXCLUSION CRITERIA:

Sickle Cell Disease

• Pain crisis requiring parenteral treatment within 4 weeks of screening/enrollment
• Blood transfusion within 60 days or exchange transfusion within 90 days of screening/enrollment
• Use of Oxbryta (voxelotor), Adakveo (crizanlizumab), and/or Endari (L-glutamine) within the 12 weeks prior to signing consent
• Women who are currently pregnant
• Presence of an arterial-venous shunt, recent axillary node dissection, or any deformity or surgical history that interferes with proper access for brachial cuff occlusion procedure of the extremities
• Mobility difficulties causing the inability to complete 6-minute walk test

Ethnically matched controls

• Women who are currently pregnant
• Presence of an arterial-venous shunt, recent axillary node dissection, or any deformity or surgical history that interferes with proper access for brachial cuff occlusion procedure of the extremities
• Mobility difficulties causing the inability to complete 6-minute walk test
• Blood transfusion within 60 days or exchange transfusion within 90 days of screening/enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: 1; Single-arm study	Diagnostic test: Non-Invasive Infrared Spectroscopy; NIRS is a non-Invasive optical technique for characterizing microvascular hemodynamics.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To quantify baseline hemodynamic function in SCD subjects at steady state utilizing NIRS in parallel with clinical assessments of cardiovascular function, including the 6-minute walk test (6MWT), pro BNP levels and transthoracic echocardiogram.	Baseline NIRS measurements will permit real time assessment of peripheral tissue hemodynamics, including oxygenation and blood flow, in relation to established markers of cardiovascular health in subjects with SCD, including the 6MWT, TTE, and pro BNP levels	120 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess baseline tissue hemodynamic function utilizing NIRS in ethnically-matched healthy control subjects without (AA) and with sickle cell trait (AS) as compared to baseline NIRS assessments in patients with SCD.	This will permit comparison of peripheral tissue hemodynamics, including blood flow and oxygenation, and cardiovascular clinical outcomes (6MWT, TTE, pro BNP) in subjects with SCD and ethnically-matched healthy volunteer subjects. NIRS results may validate abnormal tissue hemodynamic responses observed in subjects with SCD as compared to controls	120 days

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Swee Lay Thein, M.D., National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2022
• Primary Completion (Estimated): February 28, 2025
• Study Completion (Estimated): February 28, 2025

Study Registration Dates

• First Submitted: November 2, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 4, 2024

More Information

Terms related to this study

• Keywords: Hemodynamic; Six-Minute Walk Test
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 10000844; 000844-H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: .Undecided: It is not yet known if there will be a plan to make IPD available

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No