A randomized, multicenter, multicountry study to evaluate the effectiveness of florbetapir (18F) PET imaging in changing patient management and to evaluate the relationship between florbetapir (18F) PET scan status and cognitive decline

Overview

Status: Not yet recruiting
Keywords: alzheimer's , imaging , AV 45 , radiopharmaceutical , dementia
IRB Number: 00059602
Specialty: Neurology
Sub Specialties: Alzheimer's Disease

Brief Summary

This study is designed to evaluate the impact of florbetapir (18F) scan information on a treating physician’s patient management decisions. The study will also explore the impact of scan information on health economic, quality of life and clinical outcomes.

Patient Management:

The first primary objective of this study is to evaluate the effectiveness of florbetapir (18F) PET imaging in changing patient management, as defined by the treating physician.

Change in management (a composite of diagnostic testing, treatment and referral, as defined below) will be determined by comparing the intended management (pre-scan) to the observed management (during the 3 months following the scan). The hypothesis is that the proportion of subjects with a change in management from baseline to 3 months will be greater for patients randomized to receive the scan results immediately (interventional arm) vs. those who receive the scan result 12 months later (control arm). The hypothesis will be tested at a global level, and if positive, will be tested at a regional level.

Patient Prognosis:

The second primary objective of this study is to evaluate the association between scan status and cognitive decline in study patients with mild impairment of cognition as measured by Alzheimer’s Disease Assessment Scale —Cognitive subscale (ADAS-cog).

The hypothesis is that mildly impaired patients with a positive scan will have significantly greater decline than those with a negative scan after 12 months of follow up.

Protocol Amendment 1 changed the following exploratory objective to a secondary objective:

To evaluate the change in individual categories of observed individual categories of the treating physician's patient management at 3 months and intended management at baseline in the interventional arm as compared with the control arm. 

Principal Investigator: Norman Foster
Department: Alzheimer's Center
Co Investigator: Edward Zamrini
Co Investigator: Kevin Duff
Co Investigator: Richard King
Co Investigator: John Hoffman

Contact Information

Name:Joshua Amaro
Phone: 581-3986
Email: josh.amaro@hsc.utah.edu

Inclusion Criteria

Inclusion Criteria

General:

Info added per Protocol Amendment 1:  Patients currently undergoing evaluation should be enrolled in the study at a point when the treating physician judges that amyloid imaging would be clinically appropriate.

End of Protocol Amendment 1 change.

Patients must have evidence for late-life progressive cognitive decline and must have had a completed evaluation for the decline (< 18 months prior to enrollment), or must be currently undergoing evaluation for the decline.  Patients enrolling into this study may have either evidence for (A) mild impairment (not demented) or (B) dementia. Alzheimer’s disease (AD) must still be considered as a potential cause of the patient’s cognitive decline by the enrolling physician at the time of recruitment.

The enrolling physician must be, at the time of enrollment, and intend to be through the course of the study, the primary physician taking care of the patient with respect to the management of their cognitive impairment.  Patients may only be enrolled by the enrolling physician if they were referred, walk-in patients, or existing patients of the physician/practice for diagnosis and management. Patients may not be under the care of the physician exclusively for the purposes of this trial.

 Mild impairment (not demented) group:

1. Males or females ≥ 50 to < 90 years of age;

2. Have a study partner (someone with an interest in the patient’s well-being with significant interaction with patient) who provides separate consent and is willing to accompany the patient on all of the study visits;

3. Have cognitive decline verified by a study partner or cognitive impairment verified by the study physician. The cognitive decline has had limited impact on functional activities; general cognition and functional performance are sufficiently preserved such that a diagnosis of dementia cannot be made by the enrolling physician;

4. Have an MMSE score of 24 to 30 inclusive; (typically MMSE score >24 ).

5. Can tolerate a 10-minute PET scan. The Principal Investigator will carefully assess each patient and use sound medical judgment to determine whether the patient can tolerate the PET scan procedure;

6. Have the ability to cooperate and comply with all study procedures;

7. Have an enrolling physician who has less than high confidence in their diagnosis for the patient related to the cognitive decline at the time of enrollment. The level of confidence in the diagnosis should be rated by the physician as 85% or lower and should be interpreted as the physician estimating that their diagnosis will be correct in < 85% of patients with the same presentation as the patient; and

8. Ability to provide informed consent for study procedures (If the patient is ineligible to give informed consent, based on local standards, the patient’s legal representative may consent on behalf of the patient but the patient must still confirm assent. The legal representative may serve as the study partner as well).

Dementia group:

1. Males or females ≥ 50 to < 90 years of age;

2. Meet clinical criteria for dementia (i.e. cognitive decline that interferes with the ability to function at work or usual activities);

3. Have a caregiver (someone responsible for the patient’s well-being and has significant interaction with patient) who provides separate consent and is willing to accompany the patient on all of the study visits;

4. Have an MMSE score of >16; (typically MMSE score < 24)

5. Have not received a clinical examination and/or laboratory test results that strongly indicates a non-neurodegenerative cause for the patients cognitive impairment;

6. Can tolerate a 10-minute PET scan. The Principal Investigator will carefully assess each patient and use sound medical judgment to determine whether the patient can tolerate the PET scan procedure;

7. Have the ability to cooperate and comply with all study procedures;

8. Have an enrolling physician who has less than high confidence in their diagnosis for the patient related to the cognitive decline at the time of enrollment. The level of confidence in the diagnosis should be rated by the physician as 85% or lower and should be interpreted as the physician estimating that their diagnosis will be correct in < than 85% of patients with the same presentation as the patient; and

9. Ability to provide informed consent for study procedures (If the patient is incapable of giving informed consent, the patient’s legal representative may consent on behalf of the patient but the patient must still confirm assent. The legal representative may serve as the study partner as well).

Exclusion Criteria

Exclusion Criteria

Patients will be excluded from enrollment if they:

1. Have a current serious or unstable illness that in the enrolling physician’s opinion, could interfere with completion of the safety or efficacy evaluations included in this study, or has a life expectancy of less than one year;

2. The patient or enrolling physician knows the result of a previous amyloid imaging scan;

3. The patient has a known brain lesion, pathology or alternative diagnosis that strongly explains the patient’s clinical presentation;

4. Are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days;

5. Have ever participated in an experimental study with an amyloid targeting agent (e.g. anti-amyloid immunotherapy, y-secretase or β-secretase inhibitor) unless it can be documented that the patient received only placebo during the course of the trial;

6. Have had a radiopharmaceutical imaging or treatment procedure within 7 days prior to the study imaging session; or

7. Are females of childbearing potential who are not surgically sterile, not refraining from sexual activity or not using reliable methods of contraception. Females of childbearing potential must not be pregnant (negative urine β-hCG at the time of screening and negative urine β-hCG on the day of imaging) or breast feeding at screening. Females must avoid becoming pregnant, and must agree to refrain from sexual activity or to use reliable contraceptive methods such as prescribed birth control or IUD for 24 hours following administration of florbetapir (18F).

Patients will also be excluded from enrollment if their enrolling physician:

1. Does not consider Alzheimer’s disease as a potential cause of the patient’s cognitive decline. The possibility of Alzheimer’s disease as causing, at least in part, the patient’s cognitive decline must not be estimated at less than 15% by the enrolling physician;

2. Is not the primary physician taking care of the patient with respect to the management of their cognitive impairment. The enrolling physician must also, at the time of enrollment, intend to be the primary physician through the course of the study with respect to the management of their cognitive impairment. Patients may only be enrolled by the enrolling physician if they were referred, walk-in patients, or existing patients of the physician/practice for diagnosis and management. Patients may not be under the care of the physician exclusively for the purposes of this trial;

3. Cannot categorize the patient as either: a) having a documented and completed evaluation for cognitive decline that is < 18 months old; or b) currently undergoing evaluation for cognitive decline; and

4. Is unwilling to suspend all testing and other evaluation procedures between the time of the baseline evaluation of the enrolling physician’s diagnosis and management plan and the time the completion of the PET scan and receiving the report (or in the event of being randomized to the Control arm, receiving notice that no report will be issued).