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

Mild Cognitive Impairment Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00857506
• Other study ID #: 18F-AV-45-A11
• Status: Completed
• Phase: Phase 2
• First received: March 5, 2009
• Last updated: March 26, 2013
• Start date: January 2009
• Est. completion date: December 2011

Study information

• Verified date: March 2013
• Source: Avid Radiopharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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.

Exclusion Criteria:

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Cognition Disorders
• Mild Cognitive Impairment

Intervention

Drug:
• florbetapir F 18
370 Mega Becquerel (10 mCi)

Locations

Country	Name	City	State
United States	Research Site	Albany	New York
United States	Research Site	Brooksville	Florida
United States	Research Site	Costa Mesa	California
United States	Research Site	Durham	North Carolina
United States	Research Site	Hallandale Beach	Florida
United States	Research Site	Scottsdale	Arizona
United States	Research Site	Tucson	Arizona
United States	Research Site	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Avid Radiopharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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 Aß+ and Aß- 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.	Baseline and 36 months	No
Secondary	Cognitive Decline in MCI Subjects	The key secondary analyses compared the number of Aß+ and Aß- 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).	Baseline and 36 months	No
Secondary	Change in ADAS-Cog in CN and AD Subjects	This analysis compared the magnitude of change from baseline in ADAS cognitive subscale (ADAS-Cog) scores between Aß+ and Aß- 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.	Baseline and 36 months	No
Secondary	Cognitive Decline in CN and AD Subjects	The key secondary analyses compared the number of Aß+ and Aß- 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).	Baseline and 36 months	No
Secondary	Covariate Adjusted Psychometric Score Change	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.	Baseline and 36 months	No
Secondary	Correlation of Change in ADAS-Cog and SUVR	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.	Baseline and 36 months	No