Positron Emission Tomography (PET) Imaging of Brain Amyloid Compared to Post-Mortem Levels

• ClinicalTrials.gov Identifier: NCT01165554
• Recruitment Status: Completed
• First Posted: July 20, 2010
• Results First Posted: December 4, 2013
• Last Update Posted: December 4, 2013
• Sponsor: GE Healthcare
• Collaborators: i3 Statprobe; Covance
• Information provided by (Responsible Party): GE Healthcare

Study Description

Brief Summary:

To determine the level of association between quantitative regional estimates of brain uptake of [18F]flutemetamol and quantitative immunohistochemical regional estimates of brain levels of amyloid estimated from post-mortem analysis of corresponding brain tissue samples.

Condition or disease	Intervention/treatment	Phase
Brain Fibrillarab Levels	Drug: [18F] Flutemetamol	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 203 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: A Principal Open-Label Study to Compare the Brain Uptake of [18F]Flutemetamol With Brain Amyloid Levels Determined Post-Mortem
• Study Start Date: May 2010
• Actual Primary Completion Date: November 2011
• Actual Study Completion Date: November 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: [18F] Flutemetamol	Drug: [18F] Flutemetamol; Flutemetamol (18F) Injection, 111 to 370 MBq (3 to 10 mCi), single intravenous injection.; Other Name: AH110690

Outcome Measures

Primary Outcome Measures :

1. The Sensitivity of Blinded Visual Interpretations of [18F]Flutemetamol Positron Emission Tomography (PET) Images Without Anatomic Brain Images for Detecting Brain Fibrillar Amyloid β. [ Time Frame: Post flutemetamol administration. ]

   A calculation used to assess Sensitivity was (Number of Blinded Reads determined abnormal by Reader "N") divided by the (Total number of abnormal participants).

   Blinded visual interpretations of [18F]flutemetamol Positron Emission Tomography (PET) images without anatomic brain images for detecting brain fibrillar amyloid β.

Secondary Outcome Measures :

1. Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, Without Anatomic Brain Images. [ Time Frame: Post Flutemetamol administrations ]

   A calculation used to assess Specificity was (Number of Blinded Reads determined normal by Reader "N") divided by the (Total number of normal participants).

   Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, without anatomic brain images.

2. Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Abnormal, With Anatomic CT Brain Images for Reference. [ Time Frame: Post flutemetamol administration. ]
   Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as abnormal, with anatomic CT brain images for reference.
3. Blinded Visual Interpretation of Each Subject's Flutemetamol F 18 Injection Brain PET Images as Normal, With Anatomic CT Brain Images for Reference. [ Time Frame: Post flutemetamol administration. ]
   Blinded visual interpretation of each subject's Flutemetamol F 18 Injection brain PET images as normal, with anatomic CT brain images for reference.

Eligibility Criteria

• Ages Eligible for Study: 55 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• The subject has a short life expectancy (approximately 1 year or less) as estimated by the Investigator.
• The subject is 70 years of age or older if cognitively normal, or 55 years of age or older if terminal because of dementia.
• The subject's general health is adequate to undergo the study procedures.

Exclusion Criteria:

• The subject has a contraindication for PET.
• The subject has a known or suspected hypersensitivity/allergy to [18F]flutemetamol or to any of the excipients.
• The subject is unable to tolerate or cooperate with study procedures.

Contacts and Locations

Locations

United States, New Jersey

GE Healthcare

Princeton, New Jersey, United States, 08540

Sponsors and Collaborators

GE Healthcare

i3 Statprobe

Covance

Investigators

• Study Director: Paul Sherwin, MD, PhD; GE Healthcare

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Thal DR, Ronisz A, Tousseyn T, Rijal Upadhaya A, Balakrishnan K, Vandenberghe R, Vandenbulcke M, von Arnim CAF, Otto M, Beach TG, Lilja J, Heurling K, Chakrabarty A, Ismail A, Buckley C, Smith APL, Kumar S, Farrar G, Walter J. Different aspects of Alzheimer's disease-related amyloid β-peptide pathology and their relationship to amyloid positron emission tomography imaging and dementia. Acta Neuropathol Commun. 2019 Nov 14;7(1):178. doi: 10.1186/s40478-019-0837-9. Erratum in: Acta Neuropathol Commun. 2020 Aug 3;8(1):121.

Thal DR, Beach TG, Zanette M, Lilja J, Heurling K, Chakrabarty A, Ismail A, Farrar G, Buckley C, Smith APL. Estimation of amyloid distribution by [(18)F]flutemetamol PET predicts the neuropathological phase of amyloid β-protein deposition. Acta Neuropathol. 2018 Oct;136(4):557-567. doi: 10.1007/s00401-018-1897-9. Epub 2018 Aug 19.

Ikonomovic MD, Buckley CJ, Heurling K, Sherwin P, Jones PA, Zanette M, Mathis CA, Klunk WE, Chakrabarty A, Ironside J, Ismail A, Smith C, Thal DR, Beach TG, Farrar G, Smith AP. Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection. Acta Neuropathol Commun. 2016 Dec 12;4(1):130.

• Responsible Party: GE Healthcare
• ClinicalTrials.gov Identifier: NCT01165554
• Other Study ID Numbers: GE-067-007
• First Posted: July 20, 2010
• Results First Posted: December 4, 2013
• Last Update Posted: December 4, 2013
• Last Verified: November 2013

Keywords provided by GE Healthcare:

Amyloid; PET-Positron Emission Tomography; SUVR-Standard uptake value ratios

Additional relevant MeSH terms:

Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Flutemetamol; Radiopharmaceuticals; Molecular Mechanisms of Pharmacological Action