Florbetapir Calibration to the Centiloid Scale
Study Details
Study Description
Brief Summary
This study is designed to demonstrate the conversion of florbetapir (18F) Positron Emission Tomography (PET) Standard Uptake Value ratio (SUVr) to Centiloid units.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Amyloid Negative Subjects Approximately 10 cognitively normal young subjects will receive a single i.v. bolus injection of approximately 370 megabecquerel (MBq) (10 millicurie [mCi]) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB. |
Drug: Florbetapir (18F)
Other Names:
Drug: 11C-PiB
Other Names:
|
Experimental: Amyloid Positive Subjects Approximately 25 subjects with a range of amyloid density comprised of subjects clinically diagnosed with Alzheimer's Disease (AD) and subjects at risk for elevated amyloid density will receive a single i.v. bolus injection of approximately 370 MBq (10 mCi) florbetapir (18F) and a single i.v. bolus injection of approximately 555 MBq (15 mCi) 11C-PiB. |
Drug: Florbetapir (18F)
Other Names:
Drug: 11C-PiB
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Florbetapir SUVr Conversion to Centiloid Units [up to 70 minutes post injection]
Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
Secondary Outcome Measures
- Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid [up to 70 minutes post injection]
Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure.
- Variability of PET Images in Young Healthy Control Subjects. [up to 70 minutes post injection]
Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Cognitively Normal Subjects
-
Males or females ≥ 21 and ≤ 45 years of age
-
Mini-mental state examination (MMSE) ≥ 29
-
Clinically Diagnosed AD Subject
-
Males or females ≥ 50 years of age
-
Meet clinical criteria for dementia due to probable AD
-
MMSE ≥ 16 and ≤ 26
-
Possible AD Subject
-
Males or females ≥ 50 years of age
-
Meet clinical criteria for dementia due to possible AD
-
MMSE ≥ 16 and ≤ 26
-
MCI Subject
-
Males or females ≥ 60 years of age with cognitive impairment (not dementia)
-
MMSE >24 and <29
-
At Risk Elderly Subject
-
Cognitively normal males or females that are known ApoE4 carriers and ≥ 75 years of age
-
MMSE ≥ 27
Exclusion Criteria:
-
Have had or currently have a diagnosis of neurodegenerative disorders other than AD
-
Have a current serious or unstable illness that could interfere with completion of the study
-
Subject has a known brain lesion, pathology or traumatic brain injury
-
Have received or participated in a trial with investigational medications in the past 30 days
-
Have had a radiopharmaceutical imaging or treatment procedure within 7 days of study imaging session
-
Females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Research Site | Pittsburgh | Pennsylvania | United States | 15213 |
2 | Research Site | Heidelberg | Victoria | Australia | 3084 |
Sponsors and Collaborators
- Avid Radiopharmaceuticals
Investigators
- Study Chair: Chief Medical Officer, Avid Radiopharmaceuticals, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
- 18F-AV-45-A22
Study Results
Participant Flow
Recruitment Details | First subject enrolled: 14 April 2014; Last subject completed: 18 September 2015 |
---|---|
Pre-assignment Detail |
Arm/Group Title | Clincally Diagnosed AD | Possible AD | Mild Cognitive Impairment (MCI) | At Risk Elderly | Young Healthy Controls (YHC) |
---|---|---|---|---|---|
Arm/Group Description | Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) | Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease | Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater | Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal | Cognitively normal young subjects between 21 and 45 years of age (inclusive) |
Period Title: Overall Study | |||||
STARTED | 10 | 4 | 7 | 4 | 10 |
COMPLETED | 10 | 4 | 7 | 3 | 10 |
NOT COMPLETED | 0 | 0 | 0 | 1 | 0 |
Baseline Characteristics
Arm/Group Title | Clincally Diagnosed AD | Possible AD | Mild Cognitive Impairment (MCI) | At Risk Elderly | Young Healthy Controls (YHC) | Total |
---|---|---|---|---|---|---|
Arm/Group Description | Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) | Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease | Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater | Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal | Cognitively normal young subjects between 21 and 45 years of age (inclusive) | Total of all reporting groups |
Overall Participants | 10 | 4 | 7 | 4 | 10 | 35 |
Age (years) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [years] |
69.2
(4.94)
|
66
(4.76)
|
79.9
(8.47)
|
79.3
(2.5)
|
27.3
(4.83)
|
60.1
(22.28)
|
Sex: Female, Male (Count of Participants) | ||||||
Female |
5
50%
|
2
50%
|
1
14.3%
|
0
0%
|
7
70%
|
15
42.9%
|
Male |
5
50%
|
2
50%
|
6
85.7%
|
4
100%
|
3
30%
|
20
57.1%
|
Mini Mental Status Exam (units on a scale) [Mean (Standard Deviation) ] | ||||||
Mean (Standard Deviation) [units on a scale] |
23.7
(2.45)
|
21.8
(4.92)
|
26.4
(1.27)
|
29.3
(0.96)
|
29.5
(0.53)
|
26.3
(3.55)
|
Outcome Measures
Title | Florbetapir SUVr Conversion to Centiloid Units |
---|---|
Description | Conversion of florbetapir (18F) positron emission tomography (PET) standard uptake value ratio (SUVr) to Centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure. |
Time Frame | up to 70 minutes post injection |
Outcome Measure Data
Analysis Population Description |
---|
All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete a florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan. |
Arm/Group Title | Clincally Diagnosed AD | Possible AD | Mild Cognitive Impairment (MCI) | At Risk Elderly | Young Healthy Controls (YHC) |
---|---|---|---|---|---|
Arm/Group Description | Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) | Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease | Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater | Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal | Cognitively normal young subjects between 21 and 45 years of age (inclusive) |
Measure Participants | 10 | 3 | 7 | 3 | 10 |
Mean (Standard Deviation) [centiloid] |
82.44
(45.623)
|
50.75
(60.383)
|
81.19
(66.357)
|
14.93
(35.885)
|
5.24
(11.981)
|
Title | Correlation of Florbetapir (18F) Centiloid and 11C-PiB Centiloid |
---|---|
Description | Correlation coefficient between 11C-PiB and florbetapir (18F) SUVr as converted to centiloid units. The Centiloid is anchored at values of 0 and 100 corresponding to the median Pittsburgh Compound B (11C-PiB) SUVr value for a representative group of young (<45) cognitively and medically healthy control subjects (YHC) and the median SUVr value for a representative group of 11C-PiB positive patients diagnosed with Alzheimer's disease, respectively. A cortical average to cerebellum SUVr was used for this outcome measure. |
Time Frame | up to 70 minutes post injection |
Outcome Measure Data
Analysis Population Description |
---|
All participants receiving both a florbetapir and a PiB scan per protocol. One subject in the possible AD group did not complete the florbetapir scan due to excessive movement. One subject in the at risk elderly group elected to leave the study before the second PET scan. |
Arm/Group Title | Clincally Diagnosed AD | Possible AD | Mild Cognitive Impairment (MCI) | At Risk Elderly | Young Healthy Controls (YHC) |
---|---|---|---|---|---|
Arm/Group Description | Patients meeting clinical criteria for dementia due to probable Alzheimer's Disease (AD) | Patients meeting clinical criteria for dementia due to possible Alzheimer's Disease | Patients with a clinical diagnosis of Mild Cognitive Impairment (MCI) and not dementia. Age is 60 years or greater | Elderly patients, 75 years or older, who are known ApoE4 gene carriers, and cognitively normal | Cognitively normal young subjects between 21 and 45 years of age (inclusive) |
Measure Participants | 10 | 3 | 7 | 3 | 10 |
Florbetapir |
82.44
(45.623)
|
50.75
(60.383)
|
81.19
(66.357)
|
14.93
(35.885)
|
5.24
(11.981)
|
11C-PiB |
87.18
(41.105)
|
54.52
(56.511)
|
74.33
(57.597)
|
26.39
(37.464)
|
0.73
(2.414)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Clincally Diagnosed AD, Possible AD, Mild Cognitive Impairment (MCI), At Risk Elderly, Young Healthy Controls (YHC) |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | R squared |
Estimated Value | 0.907 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Variability of PET Images in Young Healthy Control Subjects. |
---|---|
Description | Coefficient of variation for 11C-PiB and florbetapir (18F) SUVr. A cortical average to cerebellum SUVr was used for this outcome measure. |
Time Frame | up to 70 minutes post injection |
Outcome Measure Data
Analysis Population Description |
---|
Young healthy controls enrolled in the study |
Arm/Group Title | PiB SUVR Variability | Florbetapir SUVR Variability |
---|---|---|
Arm/Group Description | Variability of standardized uptake value ratio (SUVR) for PiB scans in young healthy controls | Variability of standardized uptake value ratio (SUVR) for florbetapir scans in young healthy controls |
Measure Participants | 10 | 10 |
Mean (Standard Deviation) [SUVr] |
1.01
(0.026)
|
0.98
(0.066)
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Clincally Diagnosed AD |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Coefficient of Variation |
Estimated Value | 2.53 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | Possible AD |
---|---|---|
Comments | ||
Type of Statistical Test | Superiority or Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Coefficient of Variation |
Estimated Value | 6.69 | |
Confidence Interval |
(2-Sided) % to |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | within 48 hours of scan as noted by group title | |||||||
---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||||
Arm/Group Title | Florbetapir Only | PiB Only | Both | Total | ||||
Arm/Group Description | Events occurring within 48 hours following florbetapir scans only | Events occurring within 48 hours of PiB scans only | Events occurring within 48 hours of both florbetapir and PiB scans | Events following Florbetapir (florbetapir only and both) | ||||
All Cause Mortality |
||||||||
Florbetapir Only | PiB Only | Both | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
Florbetapir Only | PiB Only | Both | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/34 (0%) | 0/35 (0%) | 0/34 (0%) | 0/34 (0%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
Florbetapir Only | PiB Only | Both | Total | |||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/34 (0%) | 0/35 (0%) | 0/34 (0%) | 0/34 (0%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Name/Title | Chief Medical Officer |
---|---|
Organization | Avid Radiopharmaceuticals, Inc. |
Phone | 215-298-0700 |
clinicaloperations@avidrp.com |
- 18F-AV-45-A22