Clinical trial NCT03702816: The Relationship Between Neuropsychological Testing and MRI, PET and COBRE - Project 1: AIM 2 (GE-180)
Official title: The Relationship Between Neuropsychological Testing and MRI, PET and Blood Biomarkers in Neurodegenerative Disease (COBRE - Project 1): AIM 2
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Alzheimer Disease
Parkinson Disease
Inflammation
Keywords: neuroinflammation
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
First posted: 2018-10-11
Enrollment: 24
Sex: ALL
Minimum age (years): 55
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: All participants will receive one Flutriciclamide (18F-GE180) PET scan.
Primary purpose: DIAGNOSTIC

Brief summary: The complex pathological cascades leading to both Alzheimer's disease (AD) and Parkinson's disease (PD) involve, at various points, inflammation. Since inflammation is a treatable symptom, understanding how and when it impacts the brain, and where specifically in the brain, would offer important guidance in the development of new treatments, sorely needed in both diseases.

Microglia play an important anti-inflammatory role, and produce a substance, mitochondrial translocator protein (TSPO), whose presence can be used as a marker of regional inflammation. GE180 is a newly developed PET ligand which binds to TSPO and hence can be used in imaging studies to analyze regional inflammation in living patients. In prior studies it has shown regional specificity in multiple sclerosis and brain injury. In the current study, the investigators will be using GE180 to analyze regional and global inflammation in the brains of patients with AD and PD at a single time point.

The results of the current study will provide enriched understanding of inflammation in these conditions, and potentially provide preliminary data to inform design of future interventional trials.

Detailed description: This study will involve a cohort that is currently being established at the Cleveland Clinic Lou Ruvo Center for Brain Health. The cohort has been established under the NIH Center of Biomedical Research Excellence (COBRE) grant and involves annual collection of detailed neuropsychological testing and biomarkers (blood and neuroimaging) from all participants annually. Data are filed in a registry (CNTN). Participants include healthy controls, participants with PD (with and without mild cognitive impairment (MCI)) and patients with MCI (with or without positive florbetapir scan, which demonstrates underlying AD changes likely causing the cognitive impairment) and patients with AD. For the current study, we will focus on patients with MCI with associated underlying AD or PD.

Participants will undergo GE180 PET one time during the study. The approach to PET data collection and analysis will be similar to work done previously with an earlier generation ligand (Edison et al., 2008) and to other work with this tracer (Fan et al., 2016). Participants will complete ECGs and have their vitals taken prior to and immediately following injections. Briefly, the ligand will be injected, there will be a 90 minute uptake period, and scan acquisition will commence for 30 minutes, and will be collected in list mode and rebinned into 18 time frames post acquisition.

The total duration of the study visit will be around 4 hours, and the participants will receive $50 compensation for the visit.

Eligibility criteria: Inclusion Criteria:

1. Be enrolled in CNTN
2. Aged 55 to 90
3. Available study partners
4. Willing and able to participate in longitudinal follow-up study
5. For MCI patients, fit criteria based in Movement Disorders Task Force or NIA

Exclusion Criteria:

1. Significant neurological disorders other than AD or PD;
2. Unstable medical conditions
3. History of major psychiatric diseases
4. MRI evidence of infarction or other focal lesion or multiple lacunes
5. Clinically significant abnormalities in B12 or TSH
6. Identified as having a common polymorphism (rs6971) in the TSPO gene which has been shown to reduce binding affinity of tracers similar to GE180. This testing will be done as part of their CNTN participation.

Primary outcomes:
measure: Frontal GE180 Standardized Uptake Value Ratio (SUVR)
timeFrame: Baseline (Single scan)
measure: Cingulate GE180 Standardized Uptake Value Ratio (SUVR)
timeFrame: Baseline (Single scan)
measure: Parietal GE180 Standardized Uptake Value Ratio (SUVR)
timeFrame: Baseline (Single scan)
measure: Temporal GE180 Standardized Uptake Value Ratio (SUVR)
timeFrame: Baseline (Single scan)
measure: Whole Brain GE180 Standardized Uptake Value Ratio (SUVR)
timeFrame: Baseline (Single scan)
measure: Memory Composite Score (Z-score)
timeFrame: Baseline (Pre-scan)
measure: Executive Function Composite Score (Z-score)
timeFrame: Baseline (Pre-scan)
measure: Speed Composite Score (Z-score)
timeFrame: Baseline (Pre-scan)
measure: Language Composite Score (Z-score)
timeFrame: Baseline (Pre-scan)
measure: Dementia Rating Score
timeFrame: Baseline (Pre-scan)
measure: Montreal Cognitive Assessment Score (MoCA)
timeFrame: Baseline (Pre-scan)
Secondary outcomes:
Other outcomes:
Locations:
city: Las Vegas
country: United States
facility: Lou Ruvo Center for Brain Health
state: Nevada
Study officials:
affiliation: The Cleveland Clinic
name: Aaron R Ritter, MD
role: PRINCIPAL_INVESTIGATOR
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