PET Imaging of Brain Amyloid in Normal Pressure Hydrocephalus

Study Overview
=================
Brief Summary
-----------------
This study will determine the level of association between the quantitative estimates of brain uptake of [18F]flutemetamol and the quantitative immunohistochemical estimates of amyloid levels in biopsy samples previously obtained during shunt placement in patients who have normal pressure hydrocephalus (NPH).

Official Title
-----------------
A Principal, Open-Label, Single Center Study to Validate the Detection of Cerebral Cortical Amyloid With Flutemetamol (18F) Injection in Subjects Previously Biopsied

Conditions
-----------------
Normal Pressure Hydrocephalus

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is 50 years old or older. The subject has had a frontal lobe cortical biopsy adequate for the detection and quantitation of amyloid. Informed consent has been signed and dated by the subject/and/or subjects' legally acceptable representative, if applicable, in accordance with local regulations. Exclusion Criteria: The subject has a contraindication for MRI or PET. The subject has a known or suspected hypersensitivity/allergy to [18F]flutemetamol. The subject has participated in any clinical study using an investigational agent within 30 days of dosing.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

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

Accepts Healthy Volunteers
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1 flutemetamol<br> | Drug: [18F] Flutemetamol<br>* All subjects will receive an intravenous (IV) dose of [18F]flutemetamol (less than 10µg flutemetamol). The nominal activity of a single administration of [18F]flutemetamol will be 185 megabecquerels (MBq).<br>* Other names: AH110690;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Estimates of Brain Uptake [18F]Flutemetamol and the Quantitative Immunohistochemical (IHC) Estimates of Amyloid Levels in Biopsy Samples Previously Obtained. | Radiotracers have enabled the in-vivo imaging of amyloid-beta plaques in the brain, one of the histopathologic hallmarks of Alzheimer's disease (AD). Standardized uptake value ratio SUVR)is the quantitive measure of specific tracer uptake, normalized for the non-specific mean uptake in a reference region. SUVR is calculated as SUV_voi/SUV_ref with SUV being the integrated activity over a given time period for the volume of interest (SUV_voi) or reference region (SUV_ref). VOI means volume of interest and REF means reference region. | Post-contrast administration | 
| Comparsion Between Brain Uptake of [18F] Flutemetamol Amyloid Level From Immunohistochemistry Assay and a Stained Biopsy Tissue Specimen. | This was an amyloid level estimate measured by Immunohistochemistry assay to determine the percentage of plaque area for mAb NAB228. The Immuno-histo chemical reagent was monoclonal antibody (mAB) NAB228. This is a percentage of the area of the biopsy tissue specimen that stains positive for amyloid using NAB228. | Post-contrast administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quantitative Estimates of Amyloid Levels ( Percent % Plaque Load) for the Following 7 Subjects | Using the Precent area of Plaque values from the Primary Anaylsis, determine the association between cerebral cortical uptake of [18F] flutemetamol (as contralateral, ipsilateral, and composite SUVR values) and Immunohistochemical and histochemical-based estimates of amyloid. | Post-contrast Administration | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amyloid, NPH Normal pressure hydrocephalus, PET Positron Emission Tomography, SUVR Standard uptake value ratios