Implications for Management of PET Amyloid Classification Technology

Study Overview
=================
Brief Summary
-----------------
The main purpose of this study is to explore the impact of an amyloid positron emission tomography and computed tomography (PET/CT) scan on physician diagnosis and management, including drug management and care practices, for patients with a diagnosis of cognitive impairment. This study also intends to capture specific patient-reported outcomes related to patient burden, confidence and satisfaction. The hypothesis is that to aid early diagnosis, individuals with a diagnostically uncertain etiology for their dementia will benefit from knowledge of amyloid plaque burden status, through an alteration of patient diagnosis and management, which will lead to significant changes in patient and care partner reported outcomes.

Detailed Description
-----------------
The primary purpose of this prospective, observational study is to examine the benefit of [18F]Flutemetamol PET/CT scan in clinical practice for early diagnosis of cognitive impairment and identifying Alzheimer's disease (AD) pathology. To accomplish this, when a clinician has ordered an amyloid positron emission tomography (PET) scan, the investigators will assess the impact of [18F]Flutemetamol PET/CT scans on 1) physician diagnosis and management as it relates to care practices and drug management, and 2) patient reported outcomes in patients evaluated in the Cognitive Disorders Clinic at the University of Utah and meeting Appropriate Use Criteria (AUC) for clinical amyloid PET/CT scans. A secondary purpose is to compare the semi-quantitative assessment of amyloid plaque burden using vendor supplied software and standard visual assessment of amyloid positivity. The primary hypothesis is that, in diagnostically uncertain cases, knowledge of amyloid status as determined by amyloid PET/CT scans may alter patient diagnosis and management and lead to significant changes in patient and family reported outcomes. A secondary hypothesis is that vendor supplied semi-quantitative assessment of amyloid plaque positivity will be superior to standard visual criteria assessments. Aims: Aim 1: To assess the change in diagnosis and management including both care practices and drug management of adult patients being evaluated for cognitive deficits and meeting Appropriate Use Criteria (AUC). Aim 2: To assess the change of amyloid PET/CT scans on patient-reported outcomes involving care partner confidence and satisfaction. Aim 3: To assess the confidence of visual interpretation by using vendor supplied semi-quantitative software to assess amyloid plaque burden. Hypotheses to be Tested - Synopsis The hypothesis is that to aid early diagnosis, individuals with a diagnostically uncertain etiology for their dementia will benefit from knowledge of amyloid plaque burden status through an alteration of patient diagnosis and management, which will lead to significant changes in patient and care partner reported outcomes. Aim 1 Amyloid PET will change physician judgment of the likelihood of AD Amyloid PET will change the leading diagnosis in more than 25% of cases Amyloid PET will increase physician diagnostic confidence in the leading diagnosis Amyloid PET will change more than 25% of care practice options from pre-scan management Amyloid PET will change more than 25% of drug management options Aim 2 Care partners are more confident in the diagnosis after the scan than before the scan Care partners will be more satisfied with multidisciplinary cognitive specialty team evaluation than previous evaluation Care partners will be more satisfied with multidisciplinary cognitive specialty team evaluation with amyloid PET than than the evaluation non-specialists performed without amyloid PET Care partners will find amyloid PET not very burdensome if the doctor finds a scan helpful Based upon their experience with the amyloid PET scan, a majority of the care partners would still agree to have an amyloid PET scan performed if it were requested by the specialist Care partners will find that amyloid PET did not cause an increase in adverse reactions (scan visit) than standard routine clinic visit (post-scan visit) Care partners will find that the diagnostic clinic visit (post-scan visit) did not cause an increase in adverse reactions than the first clinic visit (pre-scan visit) Aim 3: 1. Confidence of radiologist / nuclear medicine physician interpretation of scans increases after adding quantitative analysis as compared to qualitative analysis alone This study will use [18F]Flutemetamol-PET imaging to assess and quantify the amyloid plaque burden in patients with mild cognitive impairment (MCI) or dementia of unclear etiology, according to Diagnostic Statistical Manual-IV (DSM-IV) and/or National Institutes of Aging-Alzheimer's Association criteria, verified by a dementia specialist within 24 months. The [18F]Flutemetamol-PET scans of these study participants will then be assessed using a General Electric (GE) software databases (NeuroMarQ) which contain scan data from healthy control individuals to evaluate for abnormalities in amyloid plaque burden differing from the values expected for individuals in their age range.

Official Title
-----------------
Implications for Management of PET Amyloid Classification Technology

Conditions
-----------------
Dementia, Mild Cognitive Impairment, Alzheimer's Disease

Intervention / Treatment
-----------------
* Drug: [18F]Flutemetamol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must be 45 to 90 years of age for inclusion in this research study. Confirmed diagnosis of MCI or dementia of unclear etiology, according to DSM-IV and/or National Institutes of Aging-Alzheimer's Association criteria, verified by a dementia specialist within 24 months. Meets Appropriate Use Criteria (AUC) Cognitive complaint verified by objectively confirmed cognitive impairment; The etiologic cause of cognitive impairment is uncertain after a comprehensive evaluation by a dementia specialist, including general medical and neurological examination, mental status testing including standard measures of cognitive impairment, laboratory testing, and structural neuroimaging as below; Alzheimer's disease is a diagnostic consideration; Knowledge of amyloid PET status is expected to alter diagnosis and management. MRI and/or CT of the brain within 12 months prior to enrollment; Clinical laboratory assessment within the 12 months prior to enrollment: complete blood count (CBC), standard blood chemistry profile, thyroid stimulating hormone (TSH), vitamin B12; Patient must agree to have clinical and radiographic endpoints and the results of and other laboratory information entered into a research database, as evidenced by signing the informed consent form. Patient must be postmenopausal for a minimum of one year, surgically sterile, or has been confirmed not to be pregnant by serum pregnancy test performed within 24 hours prior to research PET imaging. All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines. Exclusion Criteria: Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion. Adult patients who require monitored anesthesia for PET scanning. Patients who are too claustrophobic to undergo PET imaging. Prior participation in an amyloid vaccination clinical study at any time in the past or completion of a passive amyloid vaccination study within 6 months before screening. Patients with Normal cognition or subjective complaints that are not verified by cognitive testing. Subject's scans being ordered for one of the following reasons: Scan is being ordered solely based on a family history of dementia, presence of apolipoprotein E, or in lieu of genotyping for suspected autosomal mutation carriers; Scan being ordered for nonmedical purposes (e.g., legal, insurance coverage, or employment screening) Currently pregnant Patients who are unwilling to know the results of their PET imaging scan.

Ages Eligible for Study
-----------------
Minimum Age: 45 Years
Maximum Age: 90 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Qualifying participants<br>All consented participants referred by a dementia expert physician to receive an amyloid PET scan with [18F]Flutametamol and meeting eligibility criteria will have visual and semi-quantitative software aided scan interpretation, complete care partner questionnaires and providers will document diagnosis, diagnostic confidence, and management plan before and after the scan. | Drug: [18F]Flutemetamol<br>* amyloid PET imaging with [18F]Flutemetamol and subsequent modification of diagnosis and management<br>* Other names: Vizamyl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of care practices changed after amyloid PET scan | % of 13 care practices that differ before and after the amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of drug management options changed after amyloid PET | % of drug management options that differ before and after the amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Change in % likelihood of Alzheimer's disease (AD) diagnosis after amyloid PET scan | Difference in % of AD likelihood identified before and after the amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Proportion of change in leading diagnosis after amyloid PET | % of leading diagnosis that differ before and after amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Change in physician confidence in leading diagnosis | Difference in a 5-point scale of physician confidence in leading diagnosis before and after amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Change in care partner's confidence in diagnosis after amyloid PET | Difference in a 5-point scale of care partner confidence in diagnosis before and after amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Change in care partner satisfaction with evaluation after amyloid PET | Difference in a 5-point scale of care partner satisfaction before team care and after amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Change in care partner assessment of the quality of evaluation after amyloid PET | Difference in a 5-point scale of care partner quality before team care and after amyloid PET scan | Visit 1, 30 days prior to scan and Visit 4, 90 days after scan | 
| Proportion of care partners finding amyloid PET scan worthwhile | Proportion of care partners indicating they would agree to do an amyloid PET again on a yes/no/don't know scale | Visit 4, 90 days after scan | 
| Proportion exhibiting increased behavior disturbance during amyloid scan visit | % of patients showing a difference in the 44-point Catastrophic Reaction Scale between the median value in all non-scan visits and the value in the amyloid PET scan visit | at each visit, visits1-4, 120 days | 
| Proportion exhibiting increased behavior disturbance when the diagnosis is given | % of patients showing a difference in the 44-point Catastrophic Reaction Scale between Visit 1 and Visit 3 when learning the result of the scan | Visit 1, Visit 3, 60 days | 
| Percentage of recommended care practices adhered to after amyloid PET scan | % of care practices recommended after amyloid PET scan reported by care partner | Visit 4 90 days post scan | 
| Percentage of recommended drug management adhered to after amyloid PET scan | % of drug management options recommended after amyloid PET scan reported by care partner | Visit 4 90 days post scan | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
physician diagnosis, PET imaging, Appropriate Use Criteria, patient-reported outcomes, MCI, Dementia, amyloid PET, Alzheimer's disease, AD