The Relationship Between Neuropsychological Testing and MRI, PET and COBRE - Project 1: AIM 2 (GE-180)

NCT ID: NCT03702816

Last Updated: 2023-05-24

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-12-13

Study Completion Date

2019-09-29

Brief Summary

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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

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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.

Conditions

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Alzheimer Disease Parkinson Disease Inflammation

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

All participants will receive one Flutriciclamide (18F-GE180) PET scan.
Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

No masking

Study Groups

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Alzheimer's Disease

Alzheimer's Disease

GE180 PET Scan

Group Type EXPERIMENTAL

GE180 PET Scan

Intervention Type DRUG

GE180 PET Scan

Parkinson's Disease

Parkinson's Disease

GE180 PET Scan

Group Type EXPERIMENTAL

GE180 PET Scan

Intervention Type DRUG

GE180 PET Scan

Control

Control Group

GE180 PET Scan

Group Type EXPERIMENTAL

GE180 PET Scan

Intervention Type DRUG

GE180 PET Scan

Mild Cognitive Impairment

Mild Cognitive Impairment

GE180 PET Scan

Group Type EXPERIMENTAL

GE180 PET Scan

Intervention Type DRUG

GE180 PET Scan

Interventions

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GE180 PET Scan

GE180 PET Scan

Intervention Type DRUG

Other Intervention Names

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Flutriciclamide (F18-GE180)

Eligibility Criteria

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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.
Minimum Eligible Age

55 Years

Maximum Eligible Age

90 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Aaron Ritter, MD

OTHER

Sponsor Role lead

Responsible Party

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Aaron Ritter, MD

Director of Clinical Trials

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Aaron R Ritter, MD

Role: PRINCIPAL_INVESTIGATOR

The Cleveland Clinic

Locations

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Lou Ruvo Center for Brain Health

Las Vegas, Nevada, United States

Site Status

Countries

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United States

References

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Maphis N, Xu G, Kokiko-Cochran ON, Jiang S, Cardona A, Ransohoff RM, Lamb BT, Bhaskar K. Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain. Brain. 2015 Jun;138(Pt 6):1738-55. doi: 10.1093/brain/awv081. Epub 2015 Mar 31.

Reference Type BACKGROUND
PMID: 25833819 (View on PubMed)

Kim YS, Joh TH. Microglia, major player in the brain inflammation: their roles in the pathogenesis of Parkinson's disease. Exp Mol Med. 2006 Aug 31;38(4):333-47. doi: 10.1038/emm.2006.40.

Reference Type BACKGROUND
PMID: 16953112 (View on PubMed)

Ji K, Miyauchi J, Tsirka SE. Microglia: an active player in the regulation of synaptic activity. Neural Plast. 2013;2013:627325. doi: 10.1155/2013/627325. Epub 2013 Nov 3.

Reference Type BACKGROUND
PMID: 24303218 (View on PubMed)

Benavides J, Fage D, Carter C, Scatton B. Peripheral type benzodiazepine binding sites are a sensitive indirect index of neuronal damage. Brain Res. 1987 Sep 22;421(1-2):167-72. doi: 10.1016/0006-8993(87)91287-x.

Reference Type BACKGROUND
PMID: 2891401 (View on PubMed)

Fan Z, Calsolaro V, Atkinson RA, Femminella GD, Waldman A, Buckley C, Trigg W, Brooks DJ, Hinz R, Edison P. Flutriciclamide (18F-GE180) PET: First-in-Human PET Study of Novel Third-Generation In Vivo Marker of Human Translocator Protein. J Nucl Med. 2016 Nov;57(11):1753-1759. doi: 10.2967/jnumed.115.169078. Epub 2016 Jun 3.

Reference Type BACKGROUND
PMID: 27261523 (View on PubMed)

Chauveau F, Boutin H, Van Camp N, Dolle F, Tavitian B. Nuclear imaging of neuroinflammation: a comprehensive review of [11C]PK11195 challengers. Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2304-19. doi: 10.1007/s00259-008-0908-9. Epub 2008 Oct 1.

Reference Type BACKGROUND
PMID: 18828015 (View on PubMed)

Boutin H, Murray K, Pradillo J, Maroy R, Smigova A, Gerhard A, Jones PA, Trigg W. 18F-GE-180: a novel TSPO radiotracer compared to 11C-R-PK11195 in a preclinical model of stroke. Eur J Nucl Med Mol Imaging. 2015 Mar;42(3):503-11. doi: 10.1007/s00259-014-2939-8. Epub 2014 Oct 29.

Reference Type BACKGROUND
PMID: 25351507 (View on PubMed)

Liu B, Le KX, Park MA, Wang S, Belanger AP, Dubey S, Frost JL, Holton P, Reiser V, Jones PA, Trigg W, Di Carli MF, Lemere CA. In Vivo Detection of Age- and Disease-Related Increases in Neuroinflammation by 18F-GE180 TSPO MicroPET Imaging in Wild-Type and Alzheimer's Transgenic Mice. J Neurosci. 2015 Nov 25;35(47):15716-30. doi: 10.1523/JNEUROSCI.0996-15.2015.

Reference Type BACKGROUND
PMID: 26609163 (View on PubMed)

Calsolaro V, Edison P. Neuroinflammation in Alzheimer's disease: Current evidence and future directions. Alzheimers Dement. 2016 Jun;12(6):719-32. doi: 10.1016/j.jalz.2016.02.010. Epub 2016 May 11.

Reference Type BACKGROUND
PMID: 27179961 (View on PubMed)

Edison P, Archer HA, Gerhard A, Hinz R, Pavese N, Turkheimer FE, Hammers A, Tai YF, Fox N, Kennedy A, Rossor M, Brooks DJ. Microglia, amyloid, and cognition in Alzheimer's disease: An [11C](R)PK11195-PET and [11C]PIB-PET study. Neurobiol Dis. 2008 Dec;32(3):412-9. doi: 10.1016/j.nbd.2008.08.001. Epub 2008 Aug 15.

Reference Type BACKGROUND
PMID: 18786637 (View on PubMed)

Owen DR, Yeo AJ, Gunn RN, Song K, Wadsworth G, Lewis A, Rhodes C, Pulford DJ, Bennacef I, Parker CA, StJean PL, Cardon LR, Mooser VE, Matthews PM, Rabiner EA, Rubio JP. An 18-kDa translocator protein (TSPO) polymorphism explains differences in binding affinity of the PET radioligand PBR28. J Cereb Blood Flow Metab. 2012 Jan;32(1):1-5. doi: 10.1038/jcbfm.2011.147. Epub 2011 Oct 19.

Reference Type BACKGROUND
PMID: 22008728 (View on PubMed)

Yokokura M, Mori N, Yagi S, Yoshikawa E, Kikuchi M, Yoshihara Y, Wakuda T, Sugihara G, Takebayashi K, Suda S, Iwata Y, Ueki T, Tsuchiya KJ, Suzuki K, Nakamura K, Ouchi Y. In vivo changes in microglial activation and amyloid deposits in brain regions with hypometabolism in Alzheimer's disease. Eur J Nucl Med Mol Imaging. 2011 Feb;38(2):343-51. doi: 10.1007/s00259-010-1612-0. Epub 2010 Sep 16.

Reference Type BACKGROUND
PMID: 20844871 (View on PubMed)

Dickens AM, Vainio S, Marjamaki P, Johansson J, Lehtiniemi P, Rokka J, Rinne J, Solin O, Haaparanta-Solin M, Jones PA, Trigg W, Anthony DC, Airas L. Detection of microglial activation in an acute model of neuroinflammation using PET and radiotracers 11C-(R)-PK11195 and 18F-GE-180. J Nucl Med. 2014 Mar;55(3):466-72. doi: 10.2967/jnumed.113.125625. Epub 2014 Feb 10.

Reference Type BACKGROUND
PMID: 24516258 (View on PubMed)

Turkheimer FE, Rizzo G, Bloomfield PS, Howes O, Zanotti-Fregonara P, Bertoldo A, Veronese M. The methodology of TSPO imaging with positron emission tomography. Biochem Soc Trans. 2015 Aug;43(4):586-92. doi: 10.1042/BST20150058. Epub 2015 Aug 3.

Reference Type BACKGROUND
PMID: 26551697 (View on PubMed)

Rizzo G, Veronese M, Tonietto M, Zanotti-Fregonara P, Turkheimer FE, Bertoldo A. Kinetic modeling without accounting for the vascular component impairs the quantification of [(11)C]PBR28 brain PET data. J Cereb Blood Flow Metab. 2014 Jun;34(6):1060-9. doi: 10.1038/jcbfm.2014.55. Epub 2014 Mar 26.

Reference Type BACKGROUND
PMID: 24667911 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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15-888

Identifier Type: -

Identifier Source: org_study_id

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