Alzheimer's Disease, Frontotemporal Dementia
Conditions
Brief summary
Study 18F-AV-45-010 is designed to evaluate the cerebral uptake of florbetapir 18F as measured by PET imaging in frontotemporal disorder (FTD) in comparison to cognitively normal volunteers and subjects with Alzheimer's disease (AD).
Interventions
DRUGflorbetapir 18F
Subjects received a one-time intravenous (IV) bolus injection of 300 megabecquerels (MBq) florbetapir 18F.
DRUG18F-FDG
FTD subjects received a one-time IV bolus injection of 185 MBq of 18F-FDG.
Sponsors
Avid Radiopharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
AD: * Male or female \>= 50 years of age * Meet National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for probable AD and have a Mini Mental State Examination (MMSE) score at screening between 10 and 24 inclusive * Have a caregiver who can report on their mental status and activities of daily living (ADL) * Give informed consent or have a caregiver give consent with subject assent. FTD: * Male or female \>= 45 years of age * Meet consensus criteria for FTD and have mild to moderate disease severity. Have a caregiver who can report on their mental status and ADL * Give informed consent or have a caregiver give consent with subject assent. CN: * Male or female \>= 45 years of age * Have and MMSE \>= 29 * Give informed consent
Exclusion criteria
* Have a history or a current clinically significant neurologic disease (other than AD or FTD, as applicable), a diagnosis of other dementing/neurodegenerative disease, or a diagnosis of mixed dementia * Evidence from MRI or other biomarkers that suggests an etiology of dementia other than AD or FTD, as applicable or in the case of CN subjects evidence indicating the presence of AD, FTD or other types of neurologic pathology * Have current clinically significant cardiovascular disease, screening ECG abnormalities, psychiatric disease, endocrine or metabolic disease, pulmonary, renal or hepatic impairment, cancer or infectious disease * Have a recent history of alcohol or substance abuse or dependence * Women of childbearing potential who are not permanently surgically sterile, or are not refraining from sexual activity while not using adequate contraception. * Require medications with a narrow therapeutic window, are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days * Have ever participated in a study with an amyloid targeting agent * Have had a radiopharmaceutical imaging or treatment procedure within 7 days of the imaging, other than as defined in the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Qualitative Amyloid Image Assessment | 50-60 min after injection | Four readers blinded to all clinical information classified florbetapir Positron Emission Tomography (PET) images as either positive for amyloid or negative for amyloid. The majority read classification is presented as either positive, negative or tied. |
| Quantitative Amyloid Image Assessment | 50-60 minutes after injection | The effect of diagnostic group on mean total cortical grey matter florbetapir binding relative to cerebellar cortex is presented as standard uptake value ratios (SUVr). |
Countries
United Kingdom
Participant flow
Pre-assignment details
34 subjects were enrolled in the trial but 6 subjects did not receive florbetapir and were not included in the Overall Study period.
Participants by arm
| Arm | Count |
|---|---|
| Frontotemporal Disorder Subjects with frontotemporal disorder (FTD).
florbetapir 18F: Subjects received a one-time intravenous (IV) bolus injection of 300 megabecquerels (MBq) florbetapir 18F.
18F-FDG: FTD subjects received a one-time IV bolus injection of 185 MBq of 18F-FDG. | 8 |
| Cognitively Normal Cognitively normal (CN) subjects.
florbetapir 18F: Subjects received a one-time intravenous (IV) bolus injection of 300 megabecquerels (MBq) florbetapir 18F. | 10 |
| Alzheimer's Disease Subjects with Alzheimer's disease (AD).
florbetapir 18F: Subjects received a one-time intravenous (IV) bolus injection of 300 megabecquerels (MBq) florbetapir 18F. | 10 |
| Total | 28 |
Baseline characteristics
| Characteristic | Frontotemporal Disorder | Cognitively Normal | Alzheimer's Disease | Total |
|---|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 9.62 | 62.4 years STANDARD_DEVIATION 4.99 | 62.6 years STANDARD_DEVIATION 4.35 | 62.5 years STANDARD_DEVIATION 6.22 |
| Region of Enrollment United Kingdom | 8 participants | 10 participants | 10 participants | 28 participants |
| Sex: Female, Male Female | 0 Participants | 5 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 7 Participants | 20 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 / 8 | 0 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 8 | 0 / 10 | 0 / 10 |
Outcome results
Primary
Qualitative Amyloid Image Assessment
Four readers blinded to all clinical information classified florbetapir Positron Emission Tomography (PET) images as either positive for amyloid or negative for amyloid. The majority read classification is presented as either positive, negative or tied.
Time frame: 50-60 min after injection
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Frontotemporal Disorder | Qualitative Amyloid Image Assessment | Negative Scan | 4 participants |
| Frontotemporal Disorder | Qualitative Amyloid Image Assessment | Positive Scan | 2 participants |
| Frontotemporal Disorder | Qualitative Amyloid Image Assessment | Tie | 2 participants |
| Cognitively Normal | Qualitative Amyloid Image Assessment | Negative Scan | 8 participants |
| Cognitively Normal | Qualitative Amyloid Image Assessment | Positive Scan | 1 participants |
| Cognitively Normal | Qualitative Amyloid Image Assessment | Tie | 1 participants |
| Alzheimer's Disease | Qualitative Amyloid Image Assessment | Positive Scan | 8 participants |
| Alzheimer's Disease | Qualitative Amyloid Image Assessment | Tie | 0 participants |
| Alzheimer's Disease | Qualitative Amyloid Image Assessment | Negative Scan | 2 participants |
Primary
Quantitative Amyloid Image Assessment
The effect of diagnostic group on mean total cortical grey matter florbetapir binding relative to cerebellar cortex is presented as standard uptake value ratios (SUVr).
Time frame: 50-60 minutes after injection
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Frontotemporal Disorder | Quantitative Amyloid Image Assessment | 1.25 SUVr | Standard Deviation 0.36 |
| Cognitively Normal | Quantitative Amyloid Image Assessment | 1.29 SUVr | Standard Deviation 0.11 |
| Alzheimer's Disease | Quantitative Amyloid Image Assessment | 1.77 SUVr | Standard Deviation 0.38 |
Comparison: The effect of diagnostic group on mean cortical florbetapir binding relative to cerebellar cortex was determined.p-value: 0.002Kruskal-Wallis