Alzheimer Disease, Mild Cognitive Impairment
Conditions
Brief summary
This is a longitudinal, observational study evaluating the imaging characteristics of the tau PET radioligand \[18F\]MK-6240 in Alzheimer's disease (AD), Mild Cognitive Impairment (MCI) and Healthy Volunteer (HV) subjects. Up to 42 subjects, including approximately 28 MCI/mild AD subjects, up to 5 moderate AD subjects, and 9 similarly aged HV subjects will be consented and screened. Imaging procedures include \[11C\]PiB to evaluate amyloid deposition, \[18F\]MK-6240 PET, and structural MRI. All subjects complete an evaluable baseline \[18F\]MK-6240 PET scan, as well as scans at 6, 12 and 24 months post-baseline. If unable to complete the 6 month, 12 month, or 24 month visit, an 18 month and/or 30 month visit may instead be scheduled, totaling a maximum of four time points.
Interventions
DRUGAll Subjects
All subjects will be given the experimental tau PET radioligand \[18F\]MK-6240
Sponsors
Cerveau Technologies, Inc.
University of Wisconsin, Madison
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
for all subjects: * Signed and dated written informed consent must be obtained from the subject to enter the study and before any assessment is performed. * Pregnancy: Participant is not pregnant at the time of the PET and MRI imaging exams. Urine pregnancy tests will be conducted as needed with pre-menopausal women who are of child-bearing potential. * Willing and able to undergo study procedures and study schedule * Availability of a study partner who has frequent and sufficient contact with the subject and is able to provide accurate information regarding the subject's cognitive and functional abilities for the CDR, agrees to accompany the subject and provide information at visits or is available by phone. The study partner must have sufficient cognitive capacity, in the judgment of the investigator, to accurately report upon the subject's behavior and cognitive and functional abilities. * Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]MK-6240 imaging visit. Inclusion Criteria for Healthy Volunteers * Normal Cognition based on cognitive results at screening. * Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]MK-6240 imaging visit. * CDR global score =0 Inclusion Criteria for Subjects with a Diagnosis of MCI or Dementia Due to AD * Have screening \[11C\]PiB PET imaging demonstrating amyloid binding based on qualitative read or DVR index value \>1.20. * MMSE score 26-30 (inclusive), CDR global score 0.5 for subjects with MCI * MMSE score 22-26 (inclusive), CDR global score 0.5 or 1 for subjects with mild dementia due to AD * MMSE score 16-21 (inclusive), CDR global score 1-2 for subjects with moderate dementia due to AD * Subjects with MCI must meet 2018 research criteria for MCI (Jack et al., 2018). * Subjects with dementia must meet 2018 research criteria for dementia (Jack et al., 2018). * A structural brain MRI with no evidence of non-AD disease to account for dementia or MRI
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | Baseline to 12 months | Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Correlation Between the Change in [18F]MK-6240 Uptake and the Change in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Using Items 1-11 | Baseline to 12 months | This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The ADAS-cog is one of the most frequently used tests to measure cognition in clinical trials in AD. The first 11 items of the ADAS-cog were used for this outcome. The ADAS was developed as a two-part scale: one that measured cognitive functions and one that measured non-cognitive functions such as mood and behavior. Most current research, including this study, uses the ADAS-Cog, which is the sub-scale that measures cognitive ability. The ADAS-cog score is based on incorrect items or errors and has a range of 0-50, where lower scores indicate better cognitive functioning. |
| Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Clinical Dementia Rating Scale (CDR). | Baseline to 12 months | This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The CDR was developed primarily for use in persons with dementia of the Alzheimer type. The six domains of CDR are: Memory, Orientation, Judgment and Problem-solving, Community Affairs, Home and Hobbies, and Personal Care. Each domain is rated on a 5-point scale of functioning: 0 no impairment; 0.5 questionable impairment; 1 mild impairment; 2 moderate impairment; and 3 severe impairment. The Sum of Boxes is the score used which is simply the sum of the 6 Domain Box Scores. The range is 0-18 with lower scores indicating better cognitive function. |
| Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Mini-Mental Status Exam (MMSE) | Baseline to 12 months | This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The MMSE is a sensitive, valid and reliable 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used as screening tool for dementia. It is also used to estimate the severity and progression of cognitive impairment and to follow the course of cognitive changes in an individual over time; thus, making it an effective way to document an individual's response to treatment. The range is 0-30 with higher scores indicating better cognitive functioning. |
| Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | Baseline to 24 months | Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Healthy Volunteers As described in the study eligibility criteria:
* Normal Cognition based on cognitive results at screening.
* Healthy with no clinically relevant finding on physical examination at screening and upon reporting for the Baseline \[18F\]MK-6240 imaging visit.
* CDR global score =0 | 6 |
| Mild Cognitive Impairment As described in the study eligibility criteria:
* Have screening \[11C\]PiB PET imaging demonstrating amyloid binding based on qualitative read or DVR index value \>1.20.
* MMSE score 26-30 (inclusive), CDR global score 0.5 for subjects with MCI
* MMSE score 22-26 (inclusive), CDR global score 0.5 or 1 for subjects with mild dementia due to AD
* MMSE score 16-21 (inclusive), CDR global score 1-2 for subjects with moderate dementia due to AD
* A structural brain MRI with no evidence of non-AD disease to account for dementia or MRI exclusion criteria. | 8 |
| Dementia As described in the study eligibility criteria:
* Have screening \[11C\]PiB PET imaging demonstrating amyloid binding based on qualitative read or DVR index value \>1.20.
* MMSE score 26-30 (inclusive), CDR global score 0.5 for subjects with MCI
* MMSE score 22-26 (inclusive), CDR global score 0.5 or 1 for subjects with mild dementia due to AD
* MMSE score 16-21 (inclusive), CDR global score 1-2 for subjects with moderate dementia due to AD | 13 |
| Total | 27 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Mild Cognitive Impairment | Dementia | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 8 Participants | 12 Participants | 25 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 69.85 years | 71.60 years | 74.52 years | 72.62 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 8 Participants | 13 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 8 Participants | 13 Participants | 27 Participants |
| Region of Enrollment United States | 6 participants | 8 participants | 13 participants | 27 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 8 Participants | 13 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 5 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 6 | 0 / 8 |
| other Total, other adverse events | 3 / 13 | 1 / 6 | 0 / 8 |
| serious Total, serious adverse events | 0 / 13 | 0 / 6 | 0 / 8 |
Outcome results
Primary
Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake
Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia.
Time frame: Baseline to 12 months
Population: 26 of the 27 participants completed the 12 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | 0.00 SUVR | Standard Deviation 0.05 |
| Mild Cognitive Impairment | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | 0.10 SUVR | Standard Deviation 0.07 |
| Dementia | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | 0.12 SUVR | Standard Deviation 0.16 |
Secondary
Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake
Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia.
Time frame: Baseline to 24 months
Population: 26 of the 27 participants completed the 24 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | -.01 SUVR | Standard Deviation 0.09 |
| Mild Cognitive Impairment | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | .21 SUVR | Standard Deviation 0.16 |
| Dementia | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | .24 SUVR | Standard Deviation 0.34 |
Secondary
Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake
Composite mean SUVR across standard regions including: numerator was the entorhinal, amygdala, fusiform, inferior temporal, middle temporal cortex; denominator was the inferior cerebellum cortex. The SUVR is a ratio and has a theoretic interpretable minimum of 1.0. This primary outcome is reported by the three primary groups: Healthy Volunteers, Mild Cognitive Impairment, and Dementia.
Time frame: Baseline to 6 months
Population: 26 of the 27 participants completed the 6 month interval
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Healthy Volunteers | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | -.03 SUVR | Standard Deviation 0.04 |
| Mild Cognitive Impairment | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | -.07 SUVR | Standard Deviation 0.26 |
| Dementia | Change in [18F]MK-6240 Standard Uptake Value Ratio (SUVR) Uptake | .19 SUVR | Standard Deviation 0.33 |
Secondary
Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Clinical Dementia Rating Scale (CDR).
This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The CDR was developed primarily for use in persons with dementia of the Alzheimer type. The six domains of CDR are: Memory, Orientation, Judgment and Problem-solving, Community Affairs, Home and Hobbies, and Personal Care. Each domain is rated on a 5-point scale of functioning: 0 no impairment; 0.5 questionable impairment; 1 mild impairment; 2 moderate impairment; and 3 severe impairment. The Sum of Boxes is the score used which is simply the sum of the 6 Domain Box Scores. The range is 0-18 with lower scores indicating better cognitive function.
Time frame: Baseline to 12 months
Population: 26 of the 27 participants completed the 12 month interval
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers | Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Clinical Dementia Rating Scale (CDR). | .23 Spearman Rho |
Secondary
Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Mini-Mental Status Exam (MMSE)
This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The MMSE is a sensitive, valid and reliable 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used as screening tool for dementia. It is also used to estimate the severity and progression of cognitive impairment and to follow the course of cognitive changes in an individual over time; thus, making it an effective way to document an individual's response to treatment. The range is 0-30 with higher scores indicating better cognitive functioning.
Time frame: Baseline to 12 months
Population: 26 of the 27 participants completed the 12 month interval
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers | Correlate the Changes in [18F]MK-6240 Uptake and Changes in Clinical Cognitive Assessments by Mini-Mental Status Exam (MMSE) | .43 Spearman Rho |
Secondary
The Correlation Between the Change in [18F]MK-6240 Uptake and the Change in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Using Items 1-11
This outcome is correlational and therefore the arms/groups are collapsed to All Subjects so that we can assess the overall pattern of relationship between cognition and tau signal across the entire continuum of Alzheimer's disease. The ADAS-cog is one of the most frequently used tests to measure cognition in clinical trials in AD. The first 11 items of the ADAS-cog were used for this outcome. The ADAS was developed as a two-part scale: one that measured cognitive functions and one that measured non-cognitive functions such as mood and behavior. Most current research, including this study, uses the ADAS-Cog, which is the sub-scale that measures cognitive ability. The ADAS-cog score is based on incorrect items or errors and has a range of 0-50, where lower scores indicate better cognitive functioning.
Time frame: Baseline to 12 months
Population: 26 of the 27 participants completed the 12 month interval
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Healthy Volunteers | The Correlation Between the Change in [18F]MK-6240 Uptake and the Change in the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog) Using Items 1-11 | .02 Spearman Rho |