Florbetaben (BAY94-9172) PET (Positron Emission Tomography) Imaging in MCI (Mild Cognitive Impairment) Patients

Study Overview
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Brief Summary
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The aim of the study is to investigate whether Florbetaben (BAY94-9172)positron emission tomography (PET) is able to distinguish between subjects with mild cognitive impairment (MCI) progressing to Alzheimer's disease (AD) from those with MCI not progressing to AD.

Official Title
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ß-amyloid Imaging With BAY94-9172 Positron Emission Tomography for Early Detection of Alzheimer's Disease in Patients With Mild Cognitive Impairment

Conditions
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Alzheimer Disease, Amyloid Beta-Protein

Intervention / Treatment
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* Drug: Florbetaben (BAY94-9172)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of MCI defined as abnormal cognition on objective testing in the absence of dementia or significant functional loss. Absence of systemic or other neurological disease that may contribute to cognitive impairment or prevent follow-up over two years. Able to give written informed consent. Age >/= 60 years of age >/= 7 years of education Exclusion Criteria: Mini mental state examination (MMSE) score < 24 at baseline Clinical dementia rating (CDR) score > 0.5 at baseline Patients who receive regular medication of drugs which may adversely impact cognition (e.g. tricyclic antidepressants, antipsychotics and/or large doses of hypnotics or anxiolytics) Existing or history of cancer History of severe head trauma, brain surgery or intracranial hematoma with permanent brain lesion Lifetime history of major affective disorder, schizophrenia, or schizo-affective disorder Contraindications to MRI (Magnetic resonance imaging) Relevant history, physical or imaging findings of neurological disease other than MCI and mild depression History of severe anaphylactic reaction or high risk of allergic reaction to drugs Patient has received another investigational drug in the preceding 14 days

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Florbetaben (BAY94-9172)<br>* single 300 megabecquerel (MBq) intravenous injection 2 mL to 10 mL, at baseline, at 12 and 24 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Assessment of Neocortical SUVRs (Mean Standard Uptake Value Ratios) as a Measure of Florbetaben Uptake | Mean SUVRs were calculated for subjects who did and did not progress to Alzheimer's Disease (AD) during the study for each PET scan time point (baseline, 12 and 24 months) | 1 scanning period post injection to be evaluated at baseline, 12 months and 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Normal and Abnormal Scans in Patients With MCI Progressing to AD and Those Who do Not Progress Based on a Threshold of Neocortical SUVR=1.4 | This outcome measure showed the number of abnormal scans in subjects with MCI progressing to AD and those who did not progress compared to subjects with normal scans that did not progress and those who did progress. | 1 scanning period post injection to be evaluated at baseline, at 12 months and at 24 months | 
| Number and Proportion of Normal and Abnormal Scans Based on Brain ß-amyloid Plaque Load (BAPL) in Subjects With MCI Converting to AD and Those Who do Not Progress | At each study time point (baseline, 12 months and 24 months) PET images were obtained at 45 min and again at 90 post injection. These images were assigned a BAPL score of 1, 2 or 3 based on the reader's evaluation of the scan. A BAPL scores of 1 was considered normal, and scores of 2 and 3 were considered abnormal. These scores were compared to subjects clinical diagnosis for AD at the end of the study follow up period. | 2 scanning periods post injection to be evaluated each at baseline, at 12 months, and at 24 months | 
| Sensitivity/Specificity/Negative Predictive Value (NPV)/Positive Predictive Value (PPV) at Baseline, 12, and 24 Months in the Detection of Significant Brain ß-amyloid Plaque Load in Patients With MCI Progressing to AD Compared to Those Who do Not Progress | Sensitivity, specificity, NPV and PPV were measured based on subject BAPL scores by time point and imaging window, compared to clinical diagnosis of AD during the study period. A BAPL score of 1 was considered negative for the presence of beta-amyloid, and scores of 2 and 3 were considered positive. For this study, sensitivity was defined as the percentage of subjects with a clinical diagnosis of AD who also had a positive PET scan (BAPL score of 2 or 3) at the respective time point. Specificity was defined as the percentage of subjects with a clinical diagnosis of non-AD who also had a negative PET scan (BAPL score of 0 or 1) at the respective time point. PPV was defined as the probability that a subject with a positive PET scan would have a clinical diagnosis of AD sometime during the 2 year follow up period. NPV was defined as the probability that a subject with a negative PET scan would not have a clinical diagnosis of AD at any point during the 2 year follow up period. | 2 scanning periods post injection to be evaluated at baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MCI, Florbetaben, Amyloid beta-protein, Alzheimer's disease