Neurovascular Determinants of Cognitive Function in Adults With Sickle Cell Disease

Cognitive impairment is a poorly understood, serious, and emerging complication for adult patients with sickle cell disease. Because there is extensive microvascular damage from oxidative damage in sickle cell disease, the investigators hypothesize that this is also present in the cerebral microvasculature to cause cognitive impairment. The investigators plan to test this by correlating markers of inflammation and oxidative damage with cognitive performance and 7 Tesla brain MRI microvascular findings in these patients, with the long term goal of understanding the mechanisms and risk factors of cognitive impairment in sickle cell disease.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease

Detailed Description

The Neurovascular Determinants of Cognitive Function in Adults with Sickle Cell Disease is a study for adults 18 and older who have been diagnosed with Sickle Cell Disease (SCD). Many adult patients with SCD suffer from cognitive impairment (CI), a serious complication responsible for severe functional limitations, and whose pathogenesis, risk factors, and natural history are unknown. This research project will look at cognitive performance and 7 Tesla brain MRI findings along with markers of inflammation and oxidation to better understand the mechanism and risk factors. The investigators will complete a baseline assessment. SCD participants will be seen for follow-up at 3 and 5 years. Non-SCD participants will be seen for follow-up at 3 years. All assessments are completed at no cost and there is compensation for participation.

• Study Type: Observational
• Enrollment (Actual): 226

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

150 participants with Sickle Cell Disease (SCD) 50 participants without Sickle Cell Disease

Description

Inclusion Criteria:

1. Age 18 and above
2. Able to provide informed consent

For Non-SCD :

1. Between age 18 and 55
2. Able to provide informed consent
3. Are age, race, and gender matched to a Sickle Cell Disease study subject.

Exclusion Criteria:

1. Age less than 18 years
2. Current pregnancy or lactation

3. Any medical condition that may result in neurocognitive or brain dysfunction that is not secondary to SCD including:

   1. Diabetes mellitus
   2. Coronary artery disease
   3. Peripheral vascular disease
   4. Other causes of cerebral vasculitis such as Systemic Lupus Erythematosus (SLE)

4. Any contraindication to MRI scanning including:

   1. History of claustrophobia
   2. Presence of metallic implants such as cardiac pacemaker or implantable defibrillator, surgical aneurysm clips, or any implanted device (e.g. insulin pump, drug infusion device)
   3. Any known metal fragments embedded in the body (eg: ear implant)
   4. Neural stimulator (e.g. Transcutaneous Electrical Nerve Stimulation Unit)
   5. Metal in the eye (e.g. from machining)
   6. Any metallic foreign body, shrapnel, or bullet
   7. Inability to lie still for 30 minutes or more
5. Inability to provide direct consent
6. In a current medical or pain crisis as diagnosed by attending physician -

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
SCD participant; No intervention
Non-SCD participant; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
7 Tesla MRI	Multiple conventional and novel markers of small vessel disease will be evaluated.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammation	Blood biomarkers of inflammation will be collected	5 years
Oxidative markers	Blood biomarkers of oxidative markers will be collected.	5 years

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Enrico Novelli, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start: April 1, 2016
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: October 25, 2016
• First Posted (Estimate): October 27, 2016

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

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: 12040139

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO