PET Imaging of Brain Amyloid in Normal Pressure Hydrocephalus

• Sponsor: GE Healthcare (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01053312
• Collaborator: i3 Statprobe (Industry)
• Enrollment: 7
• Location: 1
• Arm: 1
• Duration (Months): 8
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Normal Pressure Hydrocephalus	Drug: [18F] Flutemetamol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• 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
• Study Start Date: Dec 1, 2009
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 flutemetamol	Drug: [18F] Flutemetamol; 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).; Other Names: Flutemetamol AH110690

Outcome Measures

Primary Outcome Measures

1. Quantitative Estimates of Brain Uptake [18F]Flutemetamol and the Quantitative Immunohistochemical (IHC) Estimates of Amyloid Levels in Biopsy Samples Previously Obtained. [Post-contrast administration]

   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.

2. Comparsion Between Brain Uptake of [18F] Flutemetamol Amyloid Level From Immunohistochemistry Assay and a Stained Biopsy Tissue Specimen. [Post-contrast administration]

   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.

Secondary Outcome Measures

1. Quantitative Estimates of Amyloid Levels ( Percent % Plaque Load) for the Following 7 Subjects [Post-contrast Administration]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GE Healthcare	Princeton	New Jersey	United States	08540

Sponsors and Collaborators

• GE Healthcare
• i3 Statprobe

Investigators

• Study Director: Kim A Mansfield, MS, GE Healthcare

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GE Healthcare
• ClinicalTrials.gov Identifier: NCT01053312
• Other Study ID Numbers: GE 067-008
• First Posted: Jan 21, 2010
• Last Update Posted: Jun 11, 2012
• Last Verified: Jun 1, 2012

• Keywords provided by GE Healthcare: Amyloid; NPH Normal pressure hydrocephalus; PET Positron Emission Tomography; SUVR Standard uptake value ratios
• Additional relevant MeSH terms: Hydrocephalus; Hydrocephalus, Normal Pressure; Flutemetamol

Study Results

Participant Flow

Arm/Group Title	Flutemetamol Injection
Arm/Group Description	[18F]flutemetamol (less than 10µg flutemetamol). The nominal activity of a single administration of [18F]flutemetamol will be 185 megabecquerels(MBq).
Period Title: Overall Study
STARTED	7
COMPLETED	7
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Flutemetamol Injection
Arm/Group Description	[18F]flutemetamol (less than 10µg flutemetamol). The nominal activity of a single administration of [18F]flutemetamol will be 185 megabecquerels(MBq).
Overall Participants	7
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	1 14.3%
>=65 years	6 85.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70 (8.7)
Sex: Female, Male (Count of Participants)
Female	3 42.9%
Male	4 57.1%
Region of Enrollment (participants) [Number]
United States	7 100%

Outcome Measures

1. Primary Outcome

Title	Quantitative Estimates of Brain Uptake [18F]Flutemetamol and the Quantitative Immunohistochemical (IHC) Estimates of Amyloid Levels in Biopsy Samples Previously Obtained.
Description	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.
Time Frame	Post-contrast administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subject 201-0001	Subject 201-0002	Subject 201-0003	Subject 201-0004	Subject 201-0005	Subject 201-0006	Subject 201-0007
Arm/Group Description	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.	[18F]flutemetamol Injection-less than 10µg of flutemetamol.
Measure Participants	1	1	1	1	1	1	1
Brain Region-Cerebellum-VOI surrounding biopsy	1.59	1.56	1.25	2.17	2.07	1.39	1.00
Brain Region-Cerebellum-Contralateral biopsy	1.77	1.93	1.16	2.32	2.08	1.18	0.86
Brain Region-Cerebellum-Anterior Cingulate	2.19	2.36	1.44	2.81	2.65	1.26	1.27
Brain Region-Cerebellum-Frontal Cortex	2.24	2.78	1.32	2.71	2.74	1.28	1.19
Brain Region-Cerebellum-Lateral Temporal Cortex	2.08	2.35	1.45	2.56	2.63	1.52	1.32
Brain Region-Cerebellum-Parietal Cortex	1.99	2.38	1.38	2.84	2.27	1.36	1.35
Brain Region-Cerebellum-Posterior Cortex	2.11	2.33	1.40	2.86	2.73	1.17	1.73
Brain Region-Cerebellum-Composite VOI	2.13	2.48	1.39	2.74	2.62	1.34	1.34

2. Primary Outcome

Title	Comparsion Between Brain Uptake of [18F] Flutemetamol Amyloid Level From Immunohistochemistry Assay and a Stained Biopsy Tissue Specimen.
Description	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.
Time Frame	Post-contrast administration

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Subject 201-0001	Subject 201-0002	Subject 201-0003	Subject 201-0004	Subject 201-0005	Subject 201-0006	Subject 201-0007
Arm/Group Description	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).	[18F]flutemetamol Injection-(less than 10µg of flutemetamol).
Measure Participants	1	1	1	1	1	1	1
Number [Percent plaque area]	0.127	0.447	0	1.007	0.4	0	0

3. Secondary Outcome

Title	Quantitative Estimates of Amyloid Levels ( Percent % Plaque Load) for the Following 7 Subjects
Description	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.
Time Frame	Post-contrast Administration

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Amyloid Level (Plaque Load)
Arm/Group Description	Amlyoid level estimate from the Immunohistochemistry assay: Percent plaque area (average across slides) for mAb NAB228.
Measure Participants	7
Subject-201-0001	0.127
Subject-201-0002	0.447
Subject-201-0003	0
Subject-201-0004	1.007
Subject-201-0005	0.4
Subject-201-0006	0
Subject-201-0007	0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Subject 201-0001
	Comments	Contralateral to the biopsy Site
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The level of association between SUVR and the amyloid levels was analyzed using a regression model.
Statistical Test of Hypothesis	p-Value	0.098
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	R²
	Estimated Value	0.688
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Subject 201-0001
	Comments	Ipsilateral to the biopsy Site
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The level of association between SUVR and the amyloid levels was analyzed using a regression model.
Statistical Test of Hypothesis	p-Value	0.268
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	R²
	Estimated Value	0.482
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Subject 201-0001
	Comments	Composite Region
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	The level of association between SUVR and the amyloid levels was analyzed using a regression model.
Statistical Test of Hypothesis	p-Value	0.099
	Comments
	Method	Regression, Linear
	Comments
Method of Estimation	Estimation Parameter	R²
	Estimated Value	0.685
	Confidence Interval	() %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	Flutemetamol Injection
Arm/Group Description	[18F]flutemetamol (less than 10µg flutemetamol). The nominal activity of a single administration of [18F]flutemetamol will be 185 megabecquerels(MBq).
All Cause Mortality
	Flutemetamol Injection
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Flutemetamol Injection
	Affected / at Risk (%)	# Events
Total	0/7 (0%)
Other (Not Including Serious) Adverse Events
	Flutemetamol Injection
	Affected / at Risk (%)	# Events
Total	7/7 (100%)
Investigations
Blood Pressure Increase	5/7 (71.4%)	5
Blood Glucose Decrease	1/7 (14.3%)	1
Dizziness	1/7 (14.3%)	1
Vascular disorders
Flushing	1/7 (14.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.