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

• ClinicalTrials.gov Identifier: NCT02681172
• Recruitment Status: Completed
• First Posted: February 12, 2016
• Results First Posted: November 2, 2018
• Last Update Posted: November 2, 2018
• Sponsor: Piramal Imaging Limited
• Information provided by (Responsible Party): Piramal Imaging Limited

Study Description

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

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease (AD)	Drug: Neuraceq (florbetaben 18F); Procedure: PET	Phase 4

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 218 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Health Services Research
• Official Title: Multicenter Study to Explore the Impact of Florbetaben (FBB) in Change of Diagnosis in Patients Who Are Evaluated for AD and in Whom Lumbar Puncture is Contraindicated or CSF Results Are Ambiguous
• Study Start Date: October 2015
• Actual Primary Completion Date: September 2016
• Actual Study Completion Date: November 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Neuraceq (florbetaben 18F) PET scan; A single dose of 300 Megabecquerels (8.1 millicuries) Neuraceq will be administered per subject. The applied florbetaben radioactive dose will be ± 20%.	Drug: Neuraceq (florbetaben 18F); Florbetaben 18F is given as an i.v. injection followed by a flush of sodium chloride solution to ensure full delivery of the dose.; Other Name: FBB; Procedure: PET; A brain PET scan is usually taken 90 minutes after the i.v. injection of florbetaben 18F.; Other Name: Positron Emission Tomography

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With a Change of Diagnosis Comparing Pre- and Post-scan Outcomes [ Time Frame: 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 :

1. Number of Subjects With Improved Level of Physician Confidence in Diagnosis at Visit 3 [ Time Frame: 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".
2. Number of Participants With a Change of Management Plan Comparing Pre- and Post-scan Outcomes [ Time Frame: 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.
3. Number of Subjects With Positive FBB PET Scan [ Time Frame: 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.
4. Number of Subjects With Negative FBB PET Scans [ Time Frame: 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.
5. Number of Subjects With Contraindicated or Failed Lumbar Puncture [ Time Frame: Visit 1 (baseline evaluation) ]
   Number of subjects with contraindicated or failed LP (anticoagulant therapy, thrombocytopenia, lumbar puncture failed, spinal problems)
6. Number of Subjects With Available CSF Analysis But Results Considered as Non-contributory by the Clinician [ Time Frame: Visit 1 (baseline evaluation) ]
   Non-contributory CSF results (ambiguous CSF result, CSF result inconsistent with clinical information, uninterpretable CSF result for technical reasons)
7. Number of Subjects Who Refused Lumbar Puncture. [ Time Frame: Visit 1 (baseline evaluation) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 90 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

France

Coordinating center (Hôpital de La Timone) and 18 associated centers in France

Marseille, France, 13385

Sponsors and Collaborators

Piramal Imaging Limited

Investigators

• Principal Investigator: Mathieu Ceccaldi, Prof. MD.; Hôpital de La Timone, Marseille, France
• Principal Investigator: Eric Guedj, Prof.; Hôpital de la Timone, Marseille, France

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ceccaldi M, Jonveaux T, Verger A, Krolak-Salmon P, Houzard C, Godefroy O, Shields T, Perrotin A, Gismondi R, Bullich S, Jovalekic A, Raffa N, Pasquier F, Semah F, Dubois B, Habert MO, Wallon D, Chastan M, Payoux P; NEUUS in AD study group, Stephens A, Guedj E. Added value of (18)F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study. Alzheimers Dement. 2018 Mar;14(3):293-305. doi: 10.1016/j.jalz.2017.09.009. Epub 2017 Nov 4.

• Responsible Party: Piramal Imaging Limited
• ClinicalTrials.gov Identifier: NCT02681172
• Other Study ID Numbers: FBB_01_02_2015; 2015-002606-37 ( EudraCT Number )
• First Posted: February 12, 2016
• Results First Posted: November 2, 2018
• Last Update Posted: November 2, 2018
• Last Verified: March 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Piramal Imaging Limited:

CSF; Alzheimer's Disease (AD) and related dementia; HAS recommendations

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders