Trial Outcomes & Findings for Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease (NCT NCT00528801)

Results Overview

Extent of neurocognitive dysfunction in neurologically asymptomatic adult patients with sickle cell disease as measured by WAIS-III performance IQ. This quotient is based on an average of 100, with a standard deviation of 15. The Wechsler intelligence scales are not considered adequate measures of extremely high and low intelligence (IQ scores above 160 and below 40, respectively). The performance IQ is derived from scores on seven subtests: picture completion, picture arrangement, block design, object assembly, digit symbol, matrix reasoning, and symbol search.

Recruitment status

COMPLETED

Target enrollment

212 participants

Primary outcome timeframe

Within 2 months of signing informed consent.

Results posted on

2017-03-21

Participant Flow

Patients with HB SS/SB0 were recruited from 12 sickle cell centers from Dec 2004 through May 2008. To eliminate selection bias, all eligible patients at these centers were approached. Matched peer controls of African descent were recruited from patients' community-based churches or neighborhoods, and matched for gender, age and education.

The NP Battery and the MRI could be scheduled in either order. A 4 week visit window was set between screening and the first of the two procedures. An additional 4 week window was set between the first procedure and the second.

Participant milestones

Participant milestones
Measure	Phase I: Cases These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
Overall Study STARTED	160	52
Overall Study COMPLETED	133	41
Overall Study NOT COMPLETED	27	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: Cases These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
Overall Study Withdrawal by Subject	1	1
Overall Study Protocol Violation	11	5
Overall Study Lost to Follow-up	15	4
Overall Study Administrative Reasons	0	1

Baseline Characteristics

Examining Cognitive Function and Brain Abnormalities in Adults With Sickle Cell Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: Cases n=160 Participants These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls n=52 Participants These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level	Total n=212 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	160 Participants n=5 Participants	52 Participants n=7 Participants	212 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	31.57 years STANDARD_DEVIATION 8.95 • n=5 Participants	33.10 years STANDARD_DEVIATION 10.06 • n=7 Participants	31.94 years STANDARD_DEVIATION 9.24 • n=5 Participants
Sex: Female, Male Female	100 Participants n=5 Participants	27 Participants n=7 Participants	127 Participants n=5 Participants
Sex: Female, Male Male	60 Participants n=5 Participants	25 Participants n=7 Participants	85 Participants n=5 Participants
Region of Enrollment United States	160 participants n=5 Participants	52 participants n=7 Participants	212 participants n=5 Participants

PRIMARY outcome

Timeframe: Within 2 months of signing informed consent.

Population: Per protocol, no imputation used.

Extent of neurocognitive dysfunction in neurologically asymptomatic adult patients with sickle cell disease as measured by WAIS-III performance IQ. This quotient is based on an average of 100, with a standard deviation of 15. The Wechsler intelligence scales are not considered adequate measures of extremely high and low intelligence (IQ scores above 160 and below 40, respectively). The performance IQ is derived from scores on seven subtests: picture completion, picture arrangement, block design, object assembly, digit symbol, matrix reasoning, and symbol search.

Outcome measures

Outcome measures
Measure	Phase I: Cases n=144 Participants These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls n=45 Participants These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
Wechsler Adult Intelligence Scale (WAIS)-III Performance IQ	90.6 Points on a scale Standard Deviation 12.70	95.9 Points on a scale Standard Deviation 12.13

SECONDARY outcome

Timeframe: Within 2 months of informed consent

Population: Per protocol, no imputation.

Particpants with imaging abnormalities as measured by MRI (Magnetic Resonance Imaging) specifically brain lacunae. Lacunar infarcts are 3-15 mm in diameter located at the basal ganglia, capsular and thalamic regions. Lesions located at the level of the anterior commisure are considered perivascular spaces unless \>5 mm in diameter.

Outcome measures

Outcome measures
Measure	Phase I: Cases n=144 Participants These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls n=45 Participants These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
Participants With Brain Lacunae as Measured by Clinical MRI	19 Participants	1 Participants

SECONDARY outcome

Timeframe: Within 2 months of informed consent

Population: Per protocol, no imputations.

The cortical gray matter is the gray matter of the cerebral cortex only and does not include subcortical gray matter such as hippocampus or basal ganglia.

Outcome measures

Outcome measures
Measure	Phase I: Cases n=144 Participants These are patients diagnosed with sickle cell disease (confirmed by hemoglobin electrophoresis).	Phase I: Controls n=45 Participants These are patients that do not have sickle cell disease (confirmed by hemoglobin electrophoresis); matched to cases by age, gender, and education level
Volume of Total Cortical Gray Matter as Measured by Volumetric MRI.	543.5 mL Standard Deviation 52.71	569.7 mL Standard Deviation 63.04

Adverse Events

Phase I: Cases

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Phase I: Controls

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Elliott Vichinsky, MD

Children's Hospital of Oakland and Research Institute

Phone: 510-428-3651

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place