Trial Outcomes & Findings for Measuring Brain Activity of School Age Children (NCT NCT03407729)

Last Updated: 2022-10-10

Results Overview

Assessment of dopaminergic circuits originating in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Includes right and left nucleus accumbens, right and left mamillary body, right and left hippocampus. Measured using Magnetic Resonance T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans with three-dimensional volumetrics analysis

Recruitment status

COMPLETED

Target enrollment

21 participants

Primary outcome timeframe

30 minutes

Results posted on

2022-10-10

Participant Flow

Participant milestones

Participant milestones
Measure	Post-hypoxic Former Preterm Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Overall Study STARTED	11	10
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Post-hypoxic Former Preterm Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Overall Study Lost to Follow-up	2	0
Overall Study Unable to schedule	0	3

Baseline Characteristics

Measuring Brain Activity of School Age Children

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Post-hypoxic Former Preterm n=9 Participants Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children n=7 Participants Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Total n=16 Participants Total of all reporting groups
Age, Categorical <=18 years	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 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	11.15 years STANDARD_DEVIATION 0.93 • n=5 Participants	12.13 years STANDARD_DEVIATION 2.06 • n=7 Participants	11.58 years STANDARD_DEVIATION 1.55 • n=5 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	9 participants n=5 Participants	7 participants n=7 Participants	16 participants n=5 Participants
Birth gestation	26.11 weeks STANDARD_DEVIATION 1.90 • n=5 Participants	39.00 weeks STANDARD_DEVIATION 1.00 • n=7 Participants	31.75 weeks STANDARD_DEVIATION 6.78 • n=5 Participants

PRIMARY outcome

Timeframe: 30 minutes

Population: All participants who had a usable structural magnetic resonance imaging (MRI) scan

Outcome measures

Outcome measures
Measure	Post-hypoxic Former Preterm n=9 Participants Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children n=7 Participants Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Structural Integrity of Dopaminergic Circuits right nucleus accumbens	177.25 mm^3 Standard Deviation 31.46	192.78 mm^3 Standard Deviation 16.48
Structural Integrity of Dopaminergic Circuits left nucleus accumbens	148.90 mm^3 Standard Deviation 50.12	175.93 mm^3 Standard Deviation 25.41
Structural Integrity of Dopaminergic Circuits left mamillary body	89.34 mm^3 Standard Deviation 18.18	54.78 mm^3 Standard Deviation 18.02
Structural Integrity of Dopaminergic Circuits right mamillary body	67.78 mm^3 Standard Deviation 17.34	44.70 mm^3 Standard Deviation 15.03
Structural Integrity of Dopaminergic Circuits left hippocampus	2741.09 mm^3 Standard Deviation 511.83	3419.48 mm^3 Standard Deviation 619.00
Structural Integrity of Dopaminergic Circuits right hippocampus	3329.34 mm^3 Standard Deviation 682.48	4241.03 mm^3 Standard Deviation 659.36

PRIMARY outcome

Timeframe: 30 minutes

Population: All participants who met criteria for a technically acceptable functional magnetic resonance imaging scan (less than 3mm movement artifact) were included in these analyses. FSL (FMRIB Software Library)-defined cluster sizes greater than 50 voxels, with p\<0.05, within cognitive areas of interest are included in the outcome table. That table provides the number of voxels in clusters that showed increased or decreased connectivity.

Subjects in each group were evaluated for changes in functional connectivity between the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), as evaluated by functional magnetic resonance imaging blood oxygen level dependent (fMRI-BOLD), using whole brain analysis. The measurement is increase/decrease of MRI signal intensity in a given region, thresholded at p \<0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects' scans were combined/mapped onto a standard MNI brain. Only clusters of over 50 voxels were included, and the size of the region is reported in voxel size. The averaged brains for prematurely born fMRI was subtracted from the full term treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only brain regions innervated by primary or collateral dopaminergic pathways are reported.

Outcome measures

Outcome measures
Measure	Post-hypoxic Former Preterm n=7 Participants Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children n=6 Participants Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Functional Activity During Executive Function Tasks Left thalamus	310 Cluster size (voxels)	358 Cluster size (voxels)
Functional Activity During Executive Function Tasks Left middle temporal gyrus	95 Cluster size (voxels)	75 Cluster size (voxels)

SECONDARY outcome

Timeframe: 20 minutes

Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand)

Outcome measures

Outcome measures
Measure	Post-hypoxic Former Preterm n=9 Participants Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.	Healthy Term-born Children n=7 Participants Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging, Electroencephalography, and Cognitive Performance Testing. Magnetic Resonance Imaging: MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel. Electroencephalography: EEG tracks and records brain wave patterns. A head cap with small discs and thin wires (electrodes) is placed on the scalp, and then send signals to a computer. Cognitive Performance Testing: For the Verbal n-back: During the fMRI scan, children will respond to a letter displayed on a small screen and indicate (by pushing a button) whether the letter shown is the same as a previously displayed letter. Children will repeat this test during the EEG. For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.
Cognitive Performance-Fine Motor Function	102.11 seconds Standard Deviation 42.77	82.71 seconds Standard Deviation 15.59

Adverse Events

Post-hypoxic Former Preterm

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Term-born Children

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

Dr. Michael J. Decker

Case Western Reserve University

Phone: 2163682467

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place