Alzheimer DiseasePhase 2NCT03702816
The Relationship Between Neuropsychological Testing and MRI, PET and COBRE - Project 1: AIM 2 (GE-180)
A Phase 2 study testing GE180 PET Scan in people with Alzheimer Disease and Parkinson Disease, run by Aaron Ritter, MD at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 55 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Alzheimer Disease, Parkinson Disease, Inflammation
- What is being tested?
- GE180 PET Scan
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Dec 2018to 29 Sep 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 to 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Be enrolled in CNTN
- Aged 55 to 90
- Available study partners
- Willing and able to participate in longitudinal follow-up study
- For MCI patients, fit criteria based in Movement Disorders Task Force or NIA
Who cannot join
- Significant neurological disorders other than AD or PD;
- Unstable medical conditions
- History of major psychiatric diseases
- MRI evidence of infarction or other focal lesion or multiple lacunes
- Clinically significant abnormalities in B12 or TSH
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Lou Ruvo Center for Brain Health
Las Vegas, Nevada, 89106
About this study
Official title: The Relationship Between Neuropsychological Testing and MRI, PET and Blood Biomarkers in Neurodegenerative Disease (COBRE - Project 1): AIM 2
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.
Read the 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.
- Conditions
- Alzheimer Disease, Parkinson Disease, Inflammation
- Being tested
- GE180 PET Scan
- Keywords
- neuroinflammation
- Medical subject headings
- Alzheimer Disease, Parkinson Disease, Inflammation, Neuroinflammatory Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GE180 PET ScanDrug
Also called Flutriciclamide (F18-GE180)
GE180 PET Scan
| Study group | Role | What they receive |
|---|---|---|
| Alzheimer's Disease | Experimental | Alzheimer's Disease
GE180 PET Scan Receives: Drug: GE180 PET Scan |
| Parkinson's Disease | Experimental | Parkinson's Disease
GE180 PET Scan Receives: Drug: GE180 PET Scan |
| Control | Experimental | Control Group
GE180 PET Scan Receives: Drug: GE180 PET Scan |
| Mild Cognitive Impairment | Experimental | Mild Cognitive Impairment
GE180 PET Scan Receives: Drug: GE180 PET Scan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Frontal GE180 Standardized Uptake Value Ratio (SUVR)
Frontal SUVR- GE180 binding potential in the frontal cortical ROI, as a marker of frontal neuroinflammation. Frontal neuroinflammation would be expected to relate to frontal lobe AD pathology, and given known frontal lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, and also to memory and language dysfunction, as these have executive components. Greater frontal lobe GE180 is expected to relate to poorer cognitive function.
Measured: Baseline (Single scan)
Cingulate GE180 Standardized Uptake Value Ratio (SUVR)
Cingulate SUVR- GE180 binding potential in the cingulate ROI, as a marker of cingulate neuroinflammation. Cingulate neuroinflammation would be expected to relate to cingulate AD pathology, and given known cingulate lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, with greater cingulate GE180 relating to poorer cognitive function.
Measured: Baseline (Single scan)
Parietal GE180 Standardized Uptake Value Ratio (SUVR)
Parietal SUVR - GE180 binding potential in the parietal cortical ROI, as a marker of parietal neuroinflammation. Parietal neuroinflammation would be expected to relate to parietal lobe AD pathology, and given known parietal lobe role in visual and executive system function, is hypothesized to relate to measures of visuospatial and executive skills in particular, with greater parietal lobe GE180 relating to poorer cognitive function.
Measured: Baseline (Single scan)
Temporal GE180 Standardized Uptake Value Ratio (SUVR)
Temporal SUVR-- GE180 binding potential in the temporal cortical ROI, as a marker of temporal neuroinflammation. Temporal neuroinflammation would be expected to relate to temporal lobe AD pathology, and given known temporal lobe role in memory and language system function, is hypothesized to relate to measures of memory in particular, with greater temporal lobe GE180 relating to poorer memory and language function.
Measured: Baseline (Single scan)
Whole Brain GE180 Standardized Uptake Value Ratio (SUVR)
Whole Brain GE180- GE180 binding potential in the whole brain, as a marker of global neuroinflammation. Global neuroinflammation would be expected to relate to more widespread pathology on average, and is hypothesized to relate to global measures of cognition, including the MoCA and DRS, with greater whole brain GE180 relating to poorer cognitive function overall.
Measured: Baseline (Single scan)
Memory Composite Score (Z-score)
The memory composite score is comprised from data from two gold-standard clinical measures of verbal and nonverbal memory (Rey Auditory Verbal Learning Test, delayed recall score; Brief Visuospatial Memory Test, Revised, delayed recall score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better memory function, a lower value is indicative of worse memory function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Measured: Baseline (Pre-scan)
Executive Function Composite Score (Z-score)
The executive function composite score is comprised from data from two gold-standard clinical measures of set-shifting and inhibition (Trail Making Test, part B; Delis Kaplan Executive Functioning Scale Color Word Inhibition, inhibition score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better executive function, a lower value is indicative of worse executive function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Measured: Baseline (Pre-scan)
Speed Composite Score (Z-score)
The speed composite score is comprised from data from two gold-standard clinical measures of speeded attention and psychomotor speed (Trail Making Test, part A; Symbol Digit Modalities Test, oral version). The raw score for the Symbol Digit Modalities Test, oral version is converted directly to a z-score based on published normative data. The Trail making Test, part A is corrected for age based on published normative data, resulting in a T-score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better speed function, a lower value is indicative of worse speed function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Measured: Baseline (Pre-scan)
Language Composite Score (Z-score)
The language composite score is comprised from data from two gold-standard clinical measures of confrontation naming and semantic fluency (Boston Naming Test; Animal Naming Test). The raw score for the Animal Naming Test is converted directly to a z-score based on published normative data. The Boston Naming Test is corrected for age based on published normative data, resulting in a scaled score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better language function, a lower value is indicative of worse language function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Measured: Baseline (Pre-scan)
Dementia Rating Score
DRS- The Dementia Rating Scale is a comprehensive, but relatively brief assessment of overall cognitive functioning. The measure consists of items testing memory, attention, executive skills, and visuospatial skill, for a total of 144 points. A score of less than 124 is indicative of dementia level cognitive functioning. A higher score indicates a better outcome.
Measured: Baseline (Pre-scan)
Montreal Cognitive Assessment Score (MoCA)
MoCA -The Montreal Cognitive Assessment is a brief screening tool, originally designed to detect patients with MCI in a memory disorders clinic [10]. Standard administration consists of 12 individual tasks grouped into seven cognitive domains (visuospatial/executive, naming; attention, language, abstraction, memory, and orientation). Task performance is summed generating both domain and a total score. An education correction of one point is added to the total score for individuals with 12 years of education or less. Scores range from 0-30, with a score of 26 or less indicating cognitive impairment.
Measured: Baseline (Pre-scan)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2018
- Study start13 Dec 2018
- Primary completion29 Sep 2019
- Study completion29 Sep 2019
Why it stopped: GE180 has limited Blood - brain barrier permeation, reducing its utility in neuroinflammation. COVID19 created supply chain issues, impacting enrollment.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (15)Papers the sponsor has linked to this study.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- All participants will receive one Flutriciclamide (18F-GE180) PET scan.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Aaron Ritter, MD
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Aaron Ritter, MD, The Cleveland Clinic
- Investigators
- Aaron R Ritter, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03702816
- Sponsor's protocol ID
- 15-888
- Status last verified
- Apr 2023
- First submitted
- 1 Oct 2018
- Last updated
- 24 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 25833819Kim 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.
PubMed 16953112Ji 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.
PubMed 24303218Benavides 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.
PubMed 2891401Fan 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.
PubMed 27261523Chauveau 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.
PubMed 18828015Boutin 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.
PubMed 25351507Liu 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.
PubMed 26609163Calsolaro 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.
PubMed 27179961Edison 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.
PubMed 18786637Owen 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.
PubMed 22008728Yokokura 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.
PubMed 20844871Dickens 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.
PubMed 24516258Turkheimer 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.
PubMed 26551697Rizzo 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.
PubMed 24667911
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Relationship Between Neuropsychological Testing and MRI, PET and Blood Biomarkers in Neurodegenerative Disease (COBRE - Project 1): AIM 2
- ClinicalTrials.gov ID
- NCT03702816
- Acronym / sponsor ID
- 15-888
- Conditions
- Alzheimer Disease, Parkinson Disease, Inflammation
- Keywords
- neuroinflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: GE180 has limited Blood - brain barrier permeation, reducing its utility in neuroinflammation. COVID19 created supply chain issues, impacting enrollment.
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Aaron Ritter, MDUniversity, hospital or other
- Study start
- 13 Dec 2018 (actual)
- Primary completion
- 29 Sep 2019 (actual)
- Study completion
- 29 Sep 2019 (actual)
- First posted
- 11 Oct 2018 (actual)
- Results
- Posted 24 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- All participants will receive one Flutriciclamide (18F-GE180) PET scan.
| Arm | Type | Receives |
|---|---|---|
| Alzheimer's Disease | Experimental | Drug: GE180 PET ScanAlzheimer's Disease GE180 PET Scan |
| Parkinson's Disease | Experimental | Drug: GE180 PET ScanParkinson's Disease GE180 PET Scan |
| Control | Experimental | Drug: GE180 PET ScanControl Group GE180 PET Scan |
| Mild Cognitive Impairment | Experimental | Drug: GE180 PET ScanMild Cognitive Impairment GE180 PET Scan |
Who may qualify
- Ages
- 55 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Be enrolled in CNTN
- Aged 55 to 90
- Available study partners
- Willing and able to participate in longitudinal follow-up study
- For MCI patients, fit criteria based in Movement Disorders Task Force or NIA
Key exclusion criteria (6 listed)
- Significant neurological disorders other than AD or PD;
- Unstable medical conditions
- History of major psychiatric diseases
- MRI evidence of infarction or other focal lesion or multiple lacunes
- Clinically significant abnormalities in B12 or TSH
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GE180 PET ScanAlso: Flutriciclamide (F18-GE180)GE180 PET Scan | Drug | Alzheimer's Disease, Control, Mild Cognitive Impairment, Parkinson's Disease |
Primary outcome
Frontal GE180 Standardized Uptake Value Ratio (SUVR)
Time frame: Baseline (Single scan)
Frontal SUVR- GE180 binding potential in the frontal cortical ROI, as a marker of frontal neuroinflammation. Frontal neuroinflammation would be expected to relate to frontal lobe AD pathology, and given known frontal lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, and also to memory and language dysfunction, as these have executive components. Greater frontal lobe GE180 is expected to relate to poorer cognitive function.
Cingulate GE180 Standardized Uptake Value Ratio (SUVR)
Time frame: Baseline (Single scan)
Cingulate SUVR- GE180 binding potential in the cingulate ROI, as a marker of cingulate neuroinflammation. Cingulate neuroinflammation would be expected to relate to cingulate AD pathology, and given known cingulate lobe role in executive system function, is hypothesized to relate to measures of executive function in particular, with greater cingulate GE180 relating to poorer cognitive function.
Parietal GE180 Standardized Uptake Value Ratio (SUVR)
Time frame: Baseline (Single scan)
Parietal SUVR - GE180 binding potential in the parietal cortical ROI, as a marker of parietal neuroinflammation. Parietal neuroinflammation would be expected to relate to parietal lobe AD pathology, and given known parietal lobe role in visual and executive system function, is hypothesized to relate to measures of visuospatial and executive skills in particular, with greater parietal lobe GE180 relating to poorer cognitive function.
Temporal GE180 Standardized Uptake Value Ratio (SUVR)
Time frame: Baseline (Single scan)
Temporal SUVR-- GE180 binding potential in the temporal cortical ROI, as a marker of temporal neuroinflammation. Temporal neuroinflammation would be expected to relate to temporal lobe AD pathology, and given known temporal lobe role in memory and language system function, is hypothesized to relate to measures of memory in particular, with greater temporal lobe GE180 relating to poorer memory and language function.
Whole Brain GE180 Standardized Uptake Value Ratio (SUVR)
Time frame: Baseline (Single scan)
Whole Brain GE180- GE180 binding potential in the whole brain, as a marker of global neuroinflammation. Global neuroinflammation would be expected to relate to more widespread pathology on average, and is hypothesized to relate to global measures of cognition, including the MoCA and DRS, with greater whole brain GE180 relating to poorer cognitive function overall.
Memory Composite Score (Z-score)
Time frame: Baseline (Pre-scan)
The memory composite score is comprised from data from two gold-standard clinical measures of verbal and nonverbal memory (Rey Auditory Verbal Learning Test, delayed recall score; Brief Visuospatial Memory Test, Revised, delayed recall score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better memory function, a lower value is indicative of worse memory function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Executive Function Composite Score (Z-score)
Time frame: Baseline (Pre-scan)
The executive function composite score is comprised from data from two gold-standard clinical measures of set-shifting and inhibition (Trail Making Test, part B; Delis Kaplan Executive Functioning Scale Color Word Inhibition, inhibition score). The raw score for each individual assessment is corrected for age based on published normative data for each test. These adjusted scores (T scores and/or scaled scores) are converted to z-scores, then the two z-scores are averaged together to create the composite score. A higher value is indicative of better executive function, a lower value is indicative of worse executive function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Speed Composite Score (Z-score)
Time frame: Baseline (Pre-scan)
The speed composite score is comprised from data from two gold-standard clinical measures of speeded attention and psychomotor speed (Trail Making Test, part A; Symbol Digit Modalities Test, oral version). The raw score for the Symbol Digit Modalities Test, oral version is converted directly to a z-score based on published normative data. The Trail making Test, part A is corrected for age based on published normative data, resulting in a T-score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better speed function, a lower value is indicative of worse speed function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Language Composite Score (Z-score)
Time frame: Baseline (Pre-scan)
The language composite score is comprised from data from two gold-standard clinical measures of confrontation naming and semantic fluency (Boston Naming Test; Animal Naming Test). The raw score for the Animal Naming Test is converted directly to a z-score based on published normative data. The Boston Naming Test is corrected for age based on published normative data, resulting in a scaled score, which is then converted to a z-score. Then the two z-scores are averaged together to create the composite score. A higher value is indicative of better language function, a lower value is indicative of worse language function. A z-score of 0 represents the sample mean. Composite Z-scores do not have direct clinical relevance.
Dementia Rating Score
Time frame: Baseline (Pre-scan)
DRS- The Dementia Rating Scale is a comprehensive, but relatively brief assessment of overall cognitive functioning. The measure consists of items testing memory, attention, executive skills, and visuospatial skill, for a total of 144 points. A score of less than 124 is indicative of dementia level cognitive functioning. A higher score indicates a better outcome.
Montreal Cognitive Assessment Score (MoCA)
Time frame: Baseline (Pre-scan)
MoCA -The Montreal Cognitive Assessment is a brief screening tool, originally designed to detect patients with MCI in a memory disorders clinic [10]. Standard administration consists of 12 individual tasks grouped into seven cognitive domains (visuospatial/executive, naming; attention, language, abstraction, memory, and orientation). Task performance is summed generating both domain and a total score. An education correction of one point is added to the total score for individuals with 12 years of education or less. Scores range from 0-30, with a score of 26 or less indicating cognitive impairment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 25833819Maphis 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.
- Background: PubMed 16953112Kim 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.
- Background: PubMed 24303218Ji 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.
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- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aaron R Ritter, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GE180 PET Scan in people with Alzheimer Disease and Parkinson Disease, run by Aaron Ritter, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Frontal GE180 Standardized Uptake Value Ratio (SUVR) (time frame: Baseline (Single scan)). The study lists 11 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03702816, which also lists 15 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.