Alzheimer's Disease
Conditions
Brief summary
The intent of this research protocol is to test the equivalency of two amyloid imaging drugs (C11 Pittsburgh Compound B and F18 Flutemetamol). The investigators hypothesize that there will be no significant difference in the distribution of the agents to areas of amyloid deposition in the brain or to other normal brain structures. Recent data have shown similarity in the distribution of the drugs in subjects with Alzheimer's disease (AD) or mild cognitive impairment (MCI). No comparison data of the two PET drugs in normal subjects has been published. It is important to understand differences in the images and biodistribution from the two drugs in normal subjects as nonspecific accumulation of the drugs in brain structures such as white matter appear to differ slightly and could affect image performance.
Detailed description
Some of the current thinking in regards to the pathophysiology of AD involves the production of amyloid Beta protein (AB) by secretase processing of amyloid precursor protein (APP). While AB is thought to be toxic to neurons its role leading to AD pathogenesis, this is not without debate. In any case, it appears that AB forms amyloid plaques that are largely ubiquitous in AD. Neuronal cell death as a result of the disease is another clear pathophysiologic finding. Because of the importance of these findings in the development of AD, targeted therapies are being investigated to selectively inhibit AB production and/or manipulate amyloid load. Positron emission tomography (PET) is a molecular imaging modality used to noninvasively measure functional processes of the body. A trace amount of a radiopharmaceutical is injected into a patient and the radiopharmaceutical will be taken up or localized in the body as a function of certain biological processes. The detectors of a PET scanner then measure the radiopharmaceutical distribution externally and the reconstructed PET images should represent the true distribution of the radiopharmaceutical within the body.
Interventions
DRUGC11 PiB
One time intravenous administration of 8-22 millicurie (mCi) C11 PiB
DRUGF18 Flutametamol
One time intravenous administration of 3-7 mCi F18 Flutametamol.
Sponsors
Mayo Clinic
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Males or females 30 years of age or older. 2. Subjects who have the clinical diagnosis of probable AD (30) ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR), cognitive normal elderly (30) age \>60 and cognitive normal young subjects (30) ages 30-60. 3. Normal subjects with Clinical Dementia Rating (CDR) 0-0.5 and AD subjects with CDR of 0.5 or greater.
Exclusion criteria
1. Subjects unable to lie down without moving for 30 minutes. 2. Women who are pregnant or who cannot stop breast feeding for 24 hours. 3. Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc,. 4. Subjects who are too claustrophobic to perform the tests. 5. Subject who have had previous brain irradiation, stroke or brain tumor(s)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Global Distribution of C11 PiB in the Brain | Approximately one hour after injection of positron emission tomography (PET) drug | The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel. |
| Global Distribution of F18 Flutemetamol in the Brain | Approximately one hour after injection of positron emission tomography (PET) drug | The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Mayo Clinic in Minnesota.
Pre-assignment details
89 subjects were consented, but 1 subject was a screen failure prior to assignment.
Participants by arm
| Arm | Count |
|---|---|
| Alzheimer's Disease Subjects who have the clinical diagnosis of probable AD (30) ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR).
Interventions include C11 PiB PET/CT, F-18 Flutametamol PET/CT.
C11 PiB: One time intravenous administration of 8-22 mCi C11 PiB
F18 Flutametamol: One time intravenous administration of 3-7 mCi F18 Flutametamol. | 25 |
| Cognitive Normal Elderly Cognitive Normal subjects who are greater than 60 years of age. Interventions include C11 PiB PET/CT, F-18 Flutametamol PET/CT.
C11 PiB: One time intravenous administration of 8-22 mCi C11 PiB
F18 Flutametamol: One time intravenous administration of 3-7 mCi F18 Flutametamol. | 30 |
| Cognitive Normal Young Cognitively normal subjects who are between 30-60 years old. Interventions include C11 PiB PET/CT, F-18 Flutametamol PET/CT.
C11 PiB: One time intravenous administration of 8-22 mCi C11 PiB
F18 Flutametamol: One time intravenous administration of 3-7 mCi F18 Flutametamol. | 33 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Alzheimer's Disease | Cognitive Normal Elderly | Cognitive Normal Young | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants | 30 Participants | 33 Participants | 88 Participants |
| Region of Enrollment United States | 25 participants | 30 participants | 33 participants | 86 participants |
| Sex: Female, Male Female | 12 Participants | 19 Participants | 18 Participants | 49 Participants |
| Sex: Female, Male Male | 13 Participants | 11 Participants | 15 Participants | 39 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 | 1 / 24 | 4 / 30 | 2 / 30 |
| serious Total, serious adverse events | 0 / 24 | 0 / 30 | 0 / 30 |
Outcome results
Primary
Global Distribution of C11 PiB in the Brain
The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel.
Time frame: Approximately one hour after injection of positron emission tomography (PET) drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alzheimer's Disease | Global Distribution of C11 PiB in the Brain | 2.50 standard uptake value ratio | Standard Deviation 0.53 |
| Cognitive Normal Elderly | Global Distribution of C11 PiB in the Brain | 1.47 standard uptake value ratio | Standard Deviation 0.28 |
| Cognitive Normal Young | Global Distribution of C11 PiB in the Brain | 1.23 standard uptake value ratio | Standard Deviation 0.08 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
Primary
Global Distribution of F18 Flutemetamol in the Brain
The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel.
Time frame: Approximately one hour after injection of positron emission tomography (PET) drug
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alzheimer's Disease | Global Distribution of F18 Flutemetamol in the Brain | 2.49 standard uptake value ratio | Standard Deviation 0.49 |
| Cognitive Normal Elderly | Global Distribution of F18 Flutemetamol in the Brain | 1.59 standard uptake value ratio | Standard Deviation 0.26 |
| Cognitive Normal Young | Global Distribution of F18 Flutemetamol in the Brain | 1.34 standard uptake value ratio | Standard Deviation 0.09 |
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided
p-value: <0.001t-test, 2 sided