Trial Outcomes & Findings for The Relationship Between Neuropsychological Testing and MRI, PET and COBRE - Project 1: AIM 2 (GE-180) (NCT NCT03702816)

NCT ID: NCT03702816

Last Updated: 2023-05-24

Results Overview

Frontal SUVR- GE180 binding potential in the frontal cortical ROI, as a marker of frontal neuroinflammation. Frontal neuroinflammation would be expected to relate to frontal lobe AD pathology, and given known frontal lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, and also to memory and language dysfunction, as these have executive components. Greater frontal lobe GE180 is expected to relate to poorer cognitive function.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Baseline (Single scan)

Results posted on

2023-05-24

Participant Flow

Participant milestones

Participant milestones
Measure
Control
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Overall Study
STARTED
10
7
3
4
Overall Study
COMPLETED
10
7
3
4
Overall Study
NOT COMPLETED
0
0
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Relationship Between Neuropsychological Testing and MRI, PET and COBRE - Project 1: AIM 2 (GE-180)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Total
n=24 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
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
3 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants
0 Participants
n=4 Participants
5 Participants
n=21 Participants
Age, Categorical
>=65 years
7 Participants
n=5 Participants
6 Participants
n=7 Participants
2 Participants
n=5 Participants
4 Participants
n=4 Participants
19 Participants
n=21 Participants
Age, Continuous
71.6 years
STANDARD_DEVIATION 7.96 • n=5 Participants
75.7 years
STANDARD_DEVIATION 11.22 • n=7 Participants
74 years
STANDARD_DEVIATION 10.23 • n=5 Participants
74.7 years
STANDARD_DEVIATION 3.49 • n=4 Participants
72.2 years
STANDARD_DEVIATION 8.96 • n=21 Participants
Sex: Female, Male
Female
5 Participants
n=5 Participants
3 Participants
n=7 Participants
2 Participants
n=5 Participants
0 Participants
n=4 Participants
10 Participants
n=21 Participants
Sex: Female, Male
Male
5 Participants
n=5 Participants
4 Participants
n=7 Participants
1 Participants
n=5 Participants
4 Participants
n=4 Participants
14 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
1 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
9 Participants
n=5 Participants
7 Participants
n=7 Participants
3 Participants
n=5 Participants
4 Participants
n=4 Participants
23 Participants
n=21 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Asian
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 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
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Black or African American
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
1 Participants
n=21 Participants
Race (NIH/OMB)
White
7 Participants
n=5 Participants
6 Participants
n=7 Participants
3 Participants
n=5 Participants
4 Participants
n=4 Participants
20 Participants
n=21 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Race (NIH/OMB)
Unknown or Not Reported
2 Participants
n=5 Participants
1 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
3 Participants
n=21 Participants
Region of Enrollment
United States
10 participants
n=5 Participants
7 participants
n=7 Participants
3 participants
n=5 Participants
4 participants
n=4 Participants
24 participants
n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Single scan)

Frontal SUVR- GE180 binding potential in the frontal cortical ROI, as a marker of frontal neuroinflammation. Frontal neuroinflammation would be expected to relate to frontal lobe AD pathology, and given known frontal lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, and also to memory and language dysfunction, as these have executive components. Greater frontal lobe GE180 is expected to relate to poorer cognitive function.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Frontal GE180 Standardized Uptake Value Ratio (SUVR)
0.8893 SUVR
Standard Deviation 0.058
0.9436 SUVR
Standard Deviation 0.055
0.8855 SUVR
Standard Deviation 0.036
0.8850 SUVR
Standard Deviation 0.049

PRIMARY outcome

Timeframe: Baseline (Single scan)

Cingulate SUVR- GE180 binding potential in the cingulate ROI, as a marker of cingulate neuroinflammation. Cingulate neuroinflammation would be expected to relate to cingulate AD pathology, and given known cingulate lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, with greater cingulate GE180 relating to poorer cognitive function.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Cingulate GE180 Standardized Uptake Value Ratio (SUVR)
0.9994 SUVR
Standard Deviation 0.057
1.0387 SUVR
Standard Deviation 0.036
1.0554 SUVR
Standard Deviation 0.063
0.9893 SUVR
Standard Deviation 0.092

PRIMARY outcome

Timeframe: Baseline (Single scan)

Parietal SUVR - GE180 binding potential in the parietal cortical ROI, as a marker of parietal neuroinflammation. Parietal neuroinflammation would be expected to relate to parietal lobe AD pathology, and given known parietal lobe role in visual and executive system function, is hypothesized to relate to measures of visuospatial and executive skills in particular, with greater parietal lobe GE180 relating to poorer cognitive function.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parietal GE180 Standardized Uptake Value Ratio (SUVR)
0.8701 SUVR
Standard Deviation 0.0588
0.9241 SUVR
Standard Deviation 0.043
0.8847 SUVR
Standard Deviation 0.032
0.8562 SUVR
Standard Deviation 0.032

PRIMARY outcome

Timeframe: Baseline (Single scan)

Temporal SUVR-- GE180 binding potential in the temporal cortical ROI, as a marker of temporal neuroinflammation. Temporal neuroinflammation would be expected to relate to temporal lobe AD pathology, and given known temporal lobe role in memory and language system function, is hypothesized to relate to measures of memory in particular, with greater temporal lobe GE180 relating to poorer memory and language function.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Temporal GE180 Standardized Uptake Value Ratio (SUVR)
0.9127 SUVR
Standard Deviation 0.0668
0.9779 SUVR
Standard Deviation 0.046
0.9146 SUVR
Standard Deviation 0.045
0.8899 SUVR
Standard Deviation 0.056

PRIMARY outcome

Timeframe: Baseline (Single scan)

Whole Brain GE180- GE180 binding potential in the whole brain, as a marker of global neuroinflammation. Global neuroinflammation would be expected to relate to more widespread pathology on average, and is hypothesized to relate to global measures of cognition, including the MoCA and DRS, with greater whole brain GE180 relating to poorer cognitive function overall.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Whole Brain GE180 Standardized Uptake Value Ratio (SUVR)
0.9179 SUVR
Standard Deviation 0.0545
0.9711 SUVR
Standard Deviation 0.034
0.9351 SUVR
Standard Deviation 0.010
0.9051 SUVR
Standard Deviation 0.046

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

The memory composite score is comprised from data from two gold-standard clinical measures of verbal and nonverbal memory (Rey Auditory Verbal Learning Test, delayed recall score; Brief Visuospatial Memory Test, Revised, delayed recall score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better memory function, a lower value is indicative of worse memory function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Memory Composite Score (Z-score)
0.367 z score
Standard Deviation 0.86
-0.675 z score
Standard Deviation 1.42
-2.483 z score
Standard Deviation 0.35
-0.404 z score
Standard Deviation 0.88

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

The executive function composite score is comprised from data from two gold-standard clinical measures of set-shifting and inhibition (Trail Making Test, part B; Delis Kaplan Executive Functioning Scale Color Word Inhibition, inhibition score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better executive function, a lower value is indicative of worse executive function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Executive Function Composite Score (Z-score)
0.572 z score
Standard Deviation 0.90
-0.011 z score
Standard Deviation 0.42
-1.361 z score
Standard Deviation 1.99
0.029 z score
Standard Deviation 0.90

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

The speed composite score is comprised from data from two gold-standard clinical measures of speeded attention and psychomotor speed (Trail Making Test, part A; Symbol Digit Modalities Test, oral version). The raw score for the Symbol Digit Modalities Test, oral version is converted directly to a z-score based on published normative data. The Trail making Test, part A is corrected for age based on published normative data, resulting in a T-score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better speed function, a lower value is indicative of worse speed function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Speed Composite Score (Z-score)
0.285 z score
Standard Deviation 1.28
-0.013 z score
Standard Deviation 0.78
-1.585 z score
Standard Deviation 1.06
-0.731 z score
Standard Deviation 0.60

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

The language composite score is comprised from data from two gold-standard clinical measures of confrontation naming and semantic fluency (Boston Naming Test; Animal Naming Test). The raw score for the Animal Naming Test is converted directly to a z-score based on published normative data. The Boston Naming Test is corrected for age based on published normative data, resulting in a scaled score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better language function, a lower value is indicative of worse language function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Language Composite Score (Z-score)
0.584 z score
Standard Deviation 0.857
-0.234 z score
Standard Deviation 1.12
-0.7272 z score
Standard Deviation 0.92
0.541 z score
Standard Deviation 1.18

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

DRS- The Dementia Rating Scale is a comprehensive, but relatively brief assessment of overall cognitive functioning. The measure consists of items testing memory, attention, executive skills, and visuospatial skill, for a total of 144 points. A score of less than 124 is indicative of dementia level cognitive functioning. A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Dementia Rating Score
139.2 score on a scale
Standard Deviation 2.97
130.4 score on a scale
Standard Deviation 3.87
120.3 score on a scale
Standard Deviation 12.42
139.3 score on a scale
Standard Deviation 5.25

PRIMARY outcome

Timeframe: Baseline (Pre-scan)

MoCA -The Montreal Cognitive Assessment is a brief screening tool, originally designed to detect patients with MCI in a memory disorders clinic \[10\]. Standard administration consists of 12 individual tasks grouped into seven cognitive domains (visuospatial/executive, naming; attention, language, abstraction, memory, and orientation). Task performance is summed generating both domain and a total score. An education correction of one point is added to the total score for individuals with 12 years of education or less. Scores range from 0-30, with a score of 26 or less indicating cognitive impairment.

Outcome measures

Outcome measures
Measure
Control
n=10 Participants
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 Participants
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 Participants
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 Participants
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Montreal Cognitive Assessment Score (MoCA)
26.0 score on a scale
Standard Deviation 2.36
23.4 score on a scale
Standard Deviation 2.44
18.3 score on a scale
Standard Deviation 4.73
27.5 score on a scale
Standard Deviation 1.00

Adverse Events

Control

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Mild Cognitive Impairment

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Alzheimer's Disease

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

Parkinson's Disease

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Control
n=10 participants at risk
Control Group GE180 PET Scan, 2 μg/mL IV, 185MBq
Mild Cognitive Impairment
n=7 participants at risk
Mild Cognitive Impairment GE180 PET Scan, 2 μg/mL IV, 185MBq
Alzheimer's Disease
n=3 participants at risk
Alzheimer's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Parkinson's Disease
n=4 participants at risk
Parkinson's Disease GE180 PET Scan, 2 μg/mL IV, 185MBq
Nervous system disorders
Low-Grade Headache
0.00%
0/10 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
28.6%
2/7 • Number of events 2 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
33.3%
1/3 • Number of events 1 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
0.00%
0/4 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
Gastrointestinal disorders
Mild Nausea
10.0%
1/10 • Number of events 1 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
0.00%
0/7 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
0.00%
0/3 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.
0.00%
0/4 • 24 hours
There was no anticipated risk of mortality (all-causes) during the course of the project.

Additional Information

Aaron Ritter, MD

Cleveland Clinic

Phone: 17024836000

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place