Impact of FBB PET Amyloid Imaging in Change of Diagnosis in Patients With AD

Phase 4

Completed

Conditions: Alzheimer's Disease (AD)

Interventions: Drug: Neuraceq (florbetaben 18F)
Procedure: PET

Registration Number: NCT02681172

Lead Sponsor: Piramal Imaging Limited

Brief Summary: This phase 4 study will explore, in the context of the present French clinical practice, the impact of florbetaben 18F (FBB) in patients evaluated for AD who require a biomarker for etiologic determination of the cognitive and functional impairment, but in whom:

1. lumbar puncture was not feasible for medical conditions

2. results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians

3. lumbar puncture (LP) was refused by the patient

Detailed Description: It will be conducted in an outpatient setting at the tertiary memory clinics (CMRR) in France in patients with a preliminary diagnosis based on the completion of a prior, full diagnostic workup, not more than 12 months previously - which could include, but will not be limited to brain imaging if needed (magnetic resonance imaging (MRI) or computed tomography (CT)), neuropsychological evaluation including a Mini-Mental Status Examination (MMSE), CSF examination and other examinations according to "Haute Autorité de santé" (HAS, National Authority of Health, France) Recommendations - and in whom:

1. lumbar puncture was not feasible for medical conditions

2. results of cerebrospinal fluid (CSF) analysis were considered ambiguous by treating physicians

3. lumbar puncture (LP) was refused by the patient

For all subjects the study will comprise 3 outpatient clinic visits to record information on previous work ups and to perform the FBB Positron Emission Tomography (PET) scan (Visit 1: screening/ baseline, Visit 2: PET scan, Visit 3: subject informed on the FBB PET scan result).

At Visit 1, the initial diagnosis based on previous work up will be collected and rated on a five-point Likert confidence scale by the Physician.

At Visit 2, the FBB PET scan will be performed. Adverse events will be reported during the exam and up to 7 days after the PET procedure.

At Visit 3, based on the amyloid PET scan results, change of diagnosis will be collected, in addition to physician confidence.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 218

Inclusion Criteria

Patients being evaluated for Alzheimer disease and related dementias according to the HAS recommendations (atypical dementia, early onset and rapid progressive dementia)
Patients who have previously been evaluated for AD and related dementias to whom a CSF examination was recommended in the last 12 months, but lumbar puncture was contraindicated or refused or CSF results were ambiguous, or
Patients currently being evaluated for AD and related dementias to whom a CSF examination is recommended but lumbar puncture is contraindicated or refused
Patients have a study partner who is willing and able to accompany him/her to all clinic visits for the duration of the protocol
Patients able to complete all clinical visits according to the protocol
Patients able to tolerate a 20-minute FBB PET scan
Patient or legal representative to provide informed consent for study participation, visits and data source verification.

Exclusion Criteria

The subject had a previous beta amyloid imaging scan
Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
Is currently receiving any investigational pharmaceutical product or has participated in a clinical trial with an investigational pharmaceutical product within 30 days prior to screening and/or was administered a radiopharmaceutical within 10 radioactive half-lives prior to study drug administration in this study
For females of childbearing age, a positive pregnancy test

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Neuraceq (florbetaben 18F) PET scan	PET	A single dose of 300 Megabecquerels (8.1 millicuries) Neuraceq will be administered per subject. The applied florbetaben radioactive dose will be ± 20%.
Neuraceq (florbetaben 18F) PET scan	Neuraceq (florbetaben 18F)	A single dose of 300 Megabecquerels (8.1 millicuries) Neuraceq will be administered per subject. The applied florbetaben radioactive dose will be ± 20%.

Primary Outcome Measures

Name	Time	Method
Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes	Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later)	The Physician's diagnosis was assessed before and after FBB PET scan. The initial Physician's diagnosis was collected before the PET scan, at Visit 1, based on key diagnostic results of current or previous workup. After the PET scan, the final Physician's diagnosis was collected at Visit 3, based on the amyloid PET scan results.

Secondary Outcome Measures

Name	Time	Method
Number of Subjects With Contraindicated or Failed Lumbar Puncture	Visit 1 (baseline evaluation)	Number of subjects with contraindicated or failed LP (anticoagulant therapy, thrombocytopenia, lumbar puncture failed, spinal problems)
Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3	Visit 1 (baseline evaluation) and Visit 3 (up to 6 months later)	The Physician's diagnostic confidence was rated on a five-point Likert scale before and after FBB PET scan. Likert scales consisted of the categories: "very weak", "weak", "moderate", "high", and "very high".
Number of Subjects With Negative FBB PET Scans	Visit 3 (up to 6 months after baseline evaluation)	PET image interpretation was performed locally in each centre by readers who had undergone training for appropriate interpretation of scans. Scans were interpreted as either "positive" or "negative" according to the approved visual assessment method.
Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes	Visit 1 (baseline evaluation) and Visit 3 (up to 3 months later)	For all subjects, concomitant medications were reported and any change of the management plan (e.g. new medications initiated, medications withdrawn, additional diagnostic tests ordered, referred to another specialist) was noted.
Number of Subjects With Positive FBB PET Scan	Visit 3 (up to 6 months after baseline evaluation)	PET image interpretation was performed locally in each centre by readers who had undergone training for appropriate interpretation of scans. Scans were interpreted as either "positive" or "negative" according to the approved visual assessment method.
Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician	Visit 1 (baseline evaluation)	Non-contributory CSF results (ambiguous CSF result, CSF result inconsistent with clinical information, uninterpretable CSF result for technical reasons)
Number of Subjects Who Refused Lumbar Puncture.	Visit 1 (baseline evaluation)