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

• ClinicalTrials.gov Identifier: NCT01607476
• Recruitment Status: Completed
• First Posted: May 30, 2012
• Results First Posted: November 1, 2016
• Last Update Posted: April 18, 2017
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): Val Lowe, Mayo Clinic

Tracking Information

• First Submitted Date: May 23, 2012
• First Posted Date: May 30, 2012
• Results First Submitted Date: August 2, 2016
• Results First Posted Date: November 1, 2016
• Last Update Posted Date: April 18, 2017
• Study Start Date: July 2012
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 12, 2016)

• Global Distribution of C11 PiB in the Brain [ Time Frame: Approximately one hour after injection of positron emission tomography (PET) drug ]
  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.
• Global Distribution of F18 Flutemetamol in the Brain [ Time Frame: Approximately one hour after injection of positron emission tomography (PET) drug ]
  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.

• Original Primary Outcome Measures (submitted: May 24, 2012): Distribution of C11 PiB and F18 Flutemetamol to areas of amyloid deposition in the brain. [ Time Frame: Subjects will be followed for the length of time is takes to complete the scans. ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Bridging Study of C11 Pittsburgh Compound B (PiB) and F18 Flutemetamol Brain Positron Emission Tomography (PET)
• Official Title: Bridging Study of C11 PiB and F18 Flutemetamol Brain PET
• Brief Summary: 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.

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
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Alzheimer's Disease

Intervention

• 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:

  • F18 Flutametamol PET/CT
  • Vizamyl

Study Arms

• 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.

  Interventions:

  • Drug: C11 PiB
  • Drug: F18 Flutametamol
• 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.
  Interventions:

  • Drug: C11 PiB
  • Drug: F18 Flutametamol
• 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.
  Interventions:

  • Drug: C11 PiB
  • Drug: F18 Flutametamol

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2015): 89
• Original Estimated Enrollment (submitted: May 24, 2012): 90
• Actual Study Completion Date: March 2016
• Actual Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 30 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01607476
• Other Study ID Numbers: 12-000118
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Undecided
• 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.

• Current Responsible Party: Val Lowe, Mayo Clinic
• Original Responsible Party: Same as current
• Current Study Sponsor: Mayo Clinic
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Val Lowe, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: November 2016