Evaluation of [18F] PBR111 and PET as a Marker of Inflammation in Subjects With Neurological Conditions

NCT01209156 | Completed Phase 1

• 1 other identifier: PBR111 001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The underlying goal of this study is to assess PBR-111 positron emission tomography (PET) imaging as a tool to detect microglial activation in the brain of Alzheimer disease (AD) research participants and age- and gender-matched healthy volunteers.

Conditions

Alzheimer Disease

Outcome Measures

Primary Outcomes (1)

• To evaluate the cerebral distribution of [18F]PBR-111 positron emission tomography (PET) for detection/exclusion of microglial activation in patients with Alzheimer Disease compared to healthy volunteers.

  1 year

Secondary Outcomes (2)

• To assess the dynamic uptake and washout of [18F]PBR-111, a potential imaging biomarker for inflammatory changes in brain, using positron emission tomography (PET) in Alzheimer disease subjects compared to healthy volunteers.

  1 year

• To perform blood metabolite characterization of [18F]PBR-111 in AD subjects compared to Healthy volunteers to determine the nature of metabolites in assessment of [18F]PBR-111 as a single positron computed tomography (PET) brain imaging agent.

  1 year

Study Arms (1)

Assess [18F] PBR111 and PET imaging

EXPERIMENTAL

Evaluation of PET imaging with \[18F\]PBR111 in HV and AD subjects (Proof of Mechanism)

Drug: [18F] PBR111

Interventions

[18F] PBR111 DRUG

Subjects will be injected with 5mCi (not to exceed a maximum of 5.5 mCi) of \[18F\]PBR111, followed by PET imaging.

Assess [18F] PBR111 and PET imaging

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant is 50 years or older.
• Written informed consent is obtained.
• Participants have a clinical diagnosis of probable Alzheimer disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer Disease and Related Disorders Association (NINCDS/ADRDA) criteria.
• Does not fulfill the ICC criteria for probable DLB (Appendix 3), the NINDS-AIREN for probable Vascular dementia (Appendix 5), or the Neary \[Neary et al. 1998\] criteria for FTD (Appendix 4)
• Clinical Dementia Rating Scale score ≤ 2.
• Modified Hachinski Ischemia Scale score of ≤ 4.
• MRI brain scan findings that do not reveal changes indicative of stroke and/or generalized cerebrovascular disease (e.g., the ARWMC scale) changes limited to: a white matter lesion score of 0 or 1 or 2 and a basal ganglia score of 0 or 1)
• has a caregiver willing and able to attend all study visits and perform the psychometric tests requiring the presence of a caregiver
• For females, non-child bearing potential or a negative urine or blood pregnancy test on day of \[18F\]-PBR111 injection.

You may not qualify if:

• History of significant cerebrovascular disease.
• Clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness
• Evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.
• Pregnancy
• Contraindication to MRI examination, e.g. metal implants or phobia as determined by the onsite radiologist performing the scan
• History of exposure to any radiation \>15 mSv/year (e.g. occupational or radiation therapy)
• Receiving drug therapy or other treatment that is known to lead to greatly fluctuating values of the hematological or chemical laboratory parameters or to severe side effects (e.g. chemotherapy)
• Received anti-amyloid drug therapy.
• The participant is 18 years or older, with at least 4 subjects ≥50 years.
• Written informed consent is obtained.
• Negative history of neurological or psychiatric illness based on evaluation by a research physician.
• Has no evidence of cognitive impairment as indicated by a clinical dementia rating (CDR, \[Hughes et al. 1993\]) score of 0 (zero) and a score of ≥ 28 in the Mini-Mental Status Examination (MMSE, \[Folstein et al. 1975\]) Clinical Dementia Rating score = 0.
• has MRI brain scan that has been judged as "normal (age- appropriate)" including ARWMC scale \[Wahlund et al. 2001\] scores supporting the lack of cerebrovascular disease (e.g., a white matter lesion score of 0 or 1 or 2 and a basal ganglia score of 0 or 1) and a Scheltens scale \[Scheltens et al. 1992\] verifying the lack of cerebral atrophy (e.g. bilateral temporal lobe atrophy visual score of 0 or 1)
• For females, non-child bearing potential a negative urine or blood pregnancy test on day of \[18F\]-PBR-111 injection.
• History of significant cerebrovascular disease.

Sponsors & Collaborators

• Institute for Neurodegenerative Disorders: lead

Study Sites (1)

Institute for Neurodegenerative Disorders

New Haven, Connecticut, 06510, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

2-(6-chloro-2-(4-(3-fluoropropoxy)phenyl)imidazo(1,2-a)pyridin-3-yl)-N,N-diethylacetamide

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Danna Jennings, MD

  Institute for Neurodegenerative Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 20, 2010
• First Posted: September 27, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: November 11, 2013

Record last verified: 2013-11

Locations

US (1)