Observational Study of Cognitive Outcomes for Subjects Who Have Had Prior PET Amyloid Imaging With Florbetapir F 18 (18F-AV-45)

Longitudinal Study of Long-term (36 Month) Cognitive Outcomes in Healthy Volunteers, Patients With Mild Cognitive Impairment (MCI) and Patients With Alzheimer's Disease (AD) Who Have Previously Had PET Imaging With 18F-AV-45 Injection.

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00857506

Enrollment

152

Registered

2009-03-06

Start date

2009-01-31

Completion date

2011-12-31

Last updated

2013-03-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Alzheimer's Disease, Mild Cognitive Impairment

Keywords

Cognitive outcome, 18F-AV-45 PET scan, Amyloid PET scan, Florbetapir F 18 amyloid PET scan, Normal cognition, Change in cognitive status in relation to brain amyloid on PET

Brief summary

The primary objective of this protocol is to determine if brain amyloid imaged with florbetapir F 18 (18F-AV-45) PET scans is predictive of progressive cognitive impairment during the subsequent 36 months for groups of: normal controls, mild cognitive impairment and Alzheimer's disease. Hypothesis 1: The probability a subject will experience progressive cognitive impairment within 36 months of imaging will be greater in subjects whose 18F-AV-45 PET scan was rated amyloid positive compared to subjects whose PET scan was rated amyloid negative. The secondary objective is to determine the stability, over 36 months of a clinical diagnosis, of AD in patients with an amyloid positive 18F-AV-45 PET. Hypothesis 2: The diagnosis of AD will remain unchanged in patients whose PET scan were rated as amyloid positive.

Detailed description

Study AV-45-A11 is designed to determine if brain amyloid aggregation imaged on 18F-AV-45 PET scans is predictive of progression of cognitive impairment during the subsequent 36 months. Approximately 180 subjects enrolled in a prior clinical study (AV-45-A05\[NCT00702143\]) will be offered an opportunity to be studied under this protocol. The initial visit will occur as soon as possible following the AV-45-A05(NCT00702143) imaging day. Subjects who qualify for the study and their caregiver/partners will be contacted approximately 6,12,18,24 and 36 months after PET imaging in study AV-45-A05(NCT00702143), and will undergo a standardized functional and psychometric evaluation. NOTE: This study is a clinical follow-up of subjects previously enrolled in trial 18F-AV-45-A05(NCT00702143). No new patients are being enrolled in this trial.

Interventions

DRUGflorbetapir F 18

370 Mega Becquerel (10 mCi)

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

* All subjects who enrolled in study AV-45-A05(NCT00702143), received 18F-AV-45, and completed a PET scan will be eligible to enroll in this trial.

Design outcomes

Primary

Measure	Time frame	Description
Change in ADAS-Cog for MCI Subjects	Baseline and 36 months	The primary analysis was the comparison in the magnitude of change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) between Aβ+ and Aβ- subjects in the Mild Cognitive Impairment (MCI) population at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (last observation carried forward \[LOCF\]). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.

Secondary

Measure	Time frame	Description
Cognitive Decline in MCI Subjects	Baseline and 36 months	The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the MCI population with clinically significant deterioration in ADAS-Cog (≥4) and Clinical Dementia Rating (CDR) global score (≥0.5) and conversion in diagnosis from MCI at baseline to AD or Cognitively Normal (CN) at 36 months. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).
Change in ADAS-Cog in CN and AD Subjects	Baseline and 36 months	This analysis compared the magnitude of change from baseline in ADAS cognitive subscale (ADAS-Cog) scores between Aβ+ and Aβ- subjects in the CN and AD populations at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.
Cognitive Decline in CN and AD Subjects	Baseline and 36 months	The key secondary analyses compared the number of Aβ+ and Aβ- subjects in the CN and AD populations with clinically significant deterioration in ADAS-Cog (≥4) and CDR global score (≥0.5). ADAS-Cog scores (range 0-70) indicate performance on a series of cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. CDR scores (range 0-3) quantify the severity of the symptoms of dementia where 0 indicates no cognitive impairment and 3 indicates severe dementia. Changes in ADAS-Cog and CDR scores were calculated by subtracting the baseline score from the 36 month score (LOCF).
Covariate Adjusted Psychometric Score Change	Baseline and 36 months	Change from baseline by diagnostic group in covariate-adjusted psychometric assessment scores at month 36 (LOCF). Assessments included Digit Symbol Substitution (DSS), Clinical Dementia Rating Sum of Boxes (CDR-SOB), Mini-Mental State Examination (MMSE), Wechsler Logical Memory Scale (WLMS) delayed and immediate recall, Category Verbal Fluency (CVF) animals and vegetables, Alzheimer's Disease Clinical Studies Consortium Activities of Daily Living (ADCS ADL) and Geriatric Depression Scale (GDS). The ranges for these scales are as follows: DSS (0-93), CDR-SOB (0-18), MMSE (0-30), WLMS delayed and immediate recall (0-25), CVF animals and vegetables (0-total number of relevant items named in 60 seconds), ADCS ADL (0-78) and GDS (0-15). For all scales except CDR-SOB and GDS a higher score indicates greater cognitive function. For CDR-SOB and GDS a higher score indicates increased dementia or depression, respectively.
Correlation of Change in ADAS-Cog and SUVR	Baseline and 36 months	Correlation between change from baseline to 36 month ADAS-Cog score and baseline global average SUVR by diagnostic group is provided below. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (LOCF). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance. Standard Uptake Value Ratio (SUVR) is the ratio of tracer uptake in the cortex and cerebellum. SUVR values higher than 1 indicate greater amyloid burden in the cortex as compared to the cerebellum whereas scores less than 1 indicate the opposite.

Countries

United States

Participant flow

Recruitment details

All subjects were recruited from participants in study 18F-AV-45-A05 (NCT00702143)

Participants by arm

Arm	Count
Alzheimer's Disease	31
Mild Cognitive Impairment	52
Cognitively Normal	69
Total	152

Baseline characteristics

Characteristic	Total	Alzheimer's Disease	Mild Cognitive Impairment	Cognitively Normal
Age Continuous	71.8 years STANDARD_DEVIATION 10.73	76.7 years STANDARD_DEVIATION 9.23	71.5 years STANDARD_DEVIATION 10.09	69.8 years STANDARD_DEVIATION 11.26
Region of Enrollment United States	152 participants	31 participants	52 participants	69 participants
Sex: Female, Male Female	83 Participants	13 Participants	29 Participants	41 Participants
Sex: Female, Male Male	69 Participants	18 Participants	23 Participants	28 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	0 / 0	1 / 36	1 / 50
serious Total, serious adverse events	0 / 0	1 / 36	0 / 50

Outcome results

Primary

Change in ADAS-Cog for MCI Subjects

The primary analysis was the comparison in the magnitude of change from baseline in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) between Aβ+ and Aβ- subjects in the Mild Cognitive Impairment (MCI) population at 36 months adjusting for baseline test score and age at informed consent. ADAS-Cog scores (range 0-70) indicate performance on a series of 11 cognitive tasks where 0 indicates the highest level of cognitive performance and 70 indicates the lowest level of cognitive performance. Change in ADAS-Cog scores were calculated by subtracting the baseline score from the 36 month score (last observation carried forward \[LOCF\]). A change in ADAS-Cog greater than 0 indicates a deterioration in cognitive performance whereas a change in ADAS-Cog less than 0 indicates improved cognitive performance.