Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET)

Bridging Study of C11 PiB and F18 Flutemetamol Brain PET

The intent of this research protocol is to test the equivalency of two amyloid imaging drugs (C11 Pittsburgh Compound B and F18 Flutemetamol). The investigators hypothesize that there will be no significant difference in the distribution of the agents to areas of amyloid deposition in the brain or to other normal brain structures. Recent data have shown similarity in the distribution of the drugs in subjects with Alzheimer's disease (AD) or mild cognitive impairment (MCI). No comparison data of the two PET drugs in normal subjects has been published. It is important to understand differences in the images and biodistribution from the two drugs in normal subjects as nonspecific accumulation of the drugs in brain structures such as white matter appear to differ slightly and could affect image performance.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: C11 PiB; Drug: F18 Flutametamol

Detailed Description

Some of the current thinking in regards to the pathophysiology of AD involves the production of amyloid Beta protein (AB) by secretase processing of amyloid precursor protein (APP). While AB is thought to be toxic to neurons its role leading to AD pathogenesis, this is not without debate. In any case, it appears that AB forms amyloid plaques that are largely ubiquitous in AD. Neuronal cell death as a result of the disease is another clear pathophysiologic finding. Because of the importance of these findings in the development of AD, targeted therapies are being investigated to selectively inhibit AB production and/or manipulate amyloid load.

Positron emission tomography (PET) is a molecular imaging modality used to noninvasively measure functional processes of the body. A trace amount of a radiopharmaceutical is injected into a patient and the radiopharmaceutical will be taken up or localized in the body as a function of certain biological processes. The detectors of a PET scanner then measure the radiopharmaceutical distribution externally and the reconstructed PET images should represent the true distribution of the radiopharmaceutical within the body.

• Study Type: Interventional
• Enrollment (Actual): 89
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or females 30 years of age or older.
2. Subjects who have the clinical diagnosis of probable AD (30) ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR), cognitive normal elderly (30) age >60 and cognitive normal young subjects (30) ages 30-60.
3. Normal subjects with Clinical Dementia Rating (CDR) 0-0.5 and AD subjects with CDR of 0.5 or greater.

Exclusion Criteria:

1. Subjects unable to lie down without moving for 30 minutes.
2. Women who are pregnant or who cannot stop breast feeding for 24 hours.
3. Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc,.
4. Subjects who are too claustrophobic to perform the tests.
5. Subject who have had previous brain irradiation, stroke or brain tumor(s)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alzheimer's Disease; Subjects who have the clinical diagnosis of probable AD ages 50 and older who have a study partner who is the participant's power of attorney (POA) or legally authorized representative (LAR). Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first.	Drug: C11 PiB; One time intravenous administration of 8-22 millicurie (mCi) C11 PiB; Other Names: C11 PiB PET/CT; C11 Pittsburgh Compound B; Drug: F18 Flutametamol; One time intravenous administration of 3-7 mCi F18 Flutametamol.; Other Names: Vizamyl; F18 Flutametamol PET/CT
Active Comparator: Cognitive Normal Elderly; Cognitive Normal subjects who are greater than 60 years of age. Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first.	Drug: C11 PiB; One time intravenous administration of 8-22 millicurie (mCi) C11 PiB; Other Names: C11 PiB PET/CT; C11 Pittsburgh Compound B; Drug: F18 Flutametamol; One time intravenous administration of 3-7 mCi F18 Flutametamol.; Other Names: Vizamyl; F18 Flutametamol PET/CT
Active Comparator: Cognitive Normal Young; Cognitively normal subjects who are between 30-60 years old. Interventions include C11 PiB PET/CT and F-18 Flutametamol PET/CT with C11 PiB PET/CT performed first.	Drug: C11 PiB; One time intravenous administration of 8-22 millicurie (mCi) C11 PiB; Other Names: C11 PiB PET/CT; C11 Pittsburgh Compound B; Drug: F18 Flutametamol; One time intravenous administration of 3-7 mCi F18 Flutametamol.; Other Names: Vizamyl; F18 Flutametamol PET/CT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Global Distribution of C11 PiB in the Brain	The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel.	Approximately one hour after injection of positron emission tomography (PET) drug
Global Distribution of F18 Flutemetamol in the Brain	The imaging analysts use a global atlas of the brain to measure the uptake of the radioactive tracer (or brightness) globally. This global uptake was normalized to the uptake in the cerebellar crus region of the brain to get a global Standard Uptake Value Ratio (SUVR). The cerebral crus (crus cerebri) is the anterior portion of the cerebral peduncle which contains the motor tracts. The standard uptake value (SUV) is a way of determining activity in PET imaging. The SUVR is the ratio of SUV from two different regions within the same PET image. For the SUVR, the injected activity, the body weight and the volume to mass conversion factor that are all part of the SUV calculation, cancel.	Approximately one hour after injection of positron emission tomography (PET) drug

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Investigators: Principal Investigator: Val Lowe, MD, Mayo Clinic

Study record dates

Study Major Dates

• Study Start: July 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 23, 2012
• First Submitted That Met QC Criteria: May 24, 2012
• First Posted (Estimate): May 30, 2012

Study Record Updates

• Last Update Posted (Actual): April 18, 2017
• Last Update Submitted That Met QC Criteria: March 21, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Radiopharmaceuticals; Corticosterone; Flutemetamol
• Other Study ID Numbers: 12-000118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: This study was funded by an industrial partner (GE) and discussions with the company about sharing the data will be entertained after first publications.