Study of Methodologies to Measure Blood Flow and Oxygenation in Adults With Sickle Cell Disease

A Study of Methodologies to Measure Blood Flow and Oxygenation as Potential Biomarkers in Adults With Sickle Cell Disease

The purpose of the study is to determine whether imaging techniques, such as magnetic resonance imaging (MRI), near infrared spectroscopy (NIRS), laser speckle contrast imaging (LSCI), and optical imaging (OI), can detect differences in blood flow and oxygen levels in different organ systems of participants with sickle cell disease (SCD). Differences in blood flow and oxygen levels detected by these techniques will be evaluated to determine their utility as biomarkers of clinical disease pathophysiology.

Study Overview

• Status: Completed
• Conditions: Healthy; Sickle Cell Disease

• Study Type: Observational
• Enrollment (Actual): 38

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Participants with mild to severe VOC

Description

Key Inclusion Criteria:

1. Have a diagnosis of SCD confirmed by hemoglobin analysis.

2. Be in stable clinical condition, as determined by the Investigator.

   Subjects enrolled in Part B must also meet the following eligibility criterion at Screening:

3. Receiving scheduled standard of care RBC exchange transfusion therapy, with ≥3 transfusions already received.
4. Be deemed healthy, as determined by the Investigator, based on the physical examination, medical history, vital signs, 12-lead electrocardiogram (ECG), and clinical laboratory measurements.

Key Exclusion Criteria:

1. Inability to lie still for ≥5 minutes, claustrophobia sufficient to interfere with generating reliable MRI scans, body weight exceeding 320.0 lbs., or girth exceeding the magnet bore.
2. Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects) which would be a contraindication for MRI.
3. Acute pain crisis requiring hospitalization, with a discharge ≤4 weeks prior to the first imaging visit, or when determined by the Investigator to not be at steady state.
4. Recent (≤3 months) treatment with hydroxyurea therapy.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Part A; Cohort 1- Participants with severe SCD (4-10 VOC/year) Cohort 2- Participants with milder SCD (<4-10 VOC/year) Cohort 3- Healthy volunteers Part A and B can occur in parallel
Part B; Adults with SCD receiving chronic red blood cell exchange transfusion Part A and B can occur in parallel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Blood flow in the brain of adults with severe SCD (4-10 vaso-occlusive crises [VOC]/ year) compared to healthy adults without SCD as assessed by MRI-ASL (arterial spin labeling)	Up to day 18 post screening visit

Secondary Outcome Measures

Outcome Measure	Time Frame
Kidney blood flow rates as assessed by MRI-SWI (susceptibility-weighted imaging)	Up to day 21 post screening visit
Skeletal muscle blood flow rates as assessed by NIRS	Up to day 21 post screening visit
Skin blood flow rates as assessed by LSCI	Up to day 21 post screening visit
Retinal blood flow rates as assessed by OI	Up to day 21 post screening visit
Total oxygen levels in the brain as assessed by MRI-ASL	Up to day 21 post screening visit
Total oxygen levels in the kidney as assessed by MRI-SWI	Up to day 21 post screening visit
Total oxygen levels in the muscle as assessed by NIRS	Up to day 21 post screening visit
Total oxygen levels in the skin as assessed by LSCI	Up to day 21 post screening visit
Total oxygen levels in the retina as assessed by OI	Up to day 21 post screening visit

Collaborators and Investigators

• Sponsor: Bioverativ Therapeutics Inc.
• Investigators: Study Director: Medical Director, Bioverativ Therapeutics Inc.

Study record dates

Study Major Dates

• Study Start: June 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: April 16, 2015
• First Submitted That Met QC Criteria: May 14, 2015
• First Posted (Estimate): May 19, 2015

Study Record Updates

• Last Update Posted (Actual): December 19, 2020
• Last Update Submitted That Met QC Criteria: December 16, 2020
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell
• Other Study ID Numbers: 996SC001