NCT03958630

PET Imaging of Neuroinflammation in Neurodegenerative Diseases Via a Novel Translocator Protein (TSPO) Radioligand

Terminated Phase 1 Results posted Last updated 1 May 2024

What this trial tests

Phase 1 trial testing 11C-ER176 in Dementia in 13 participants. Terminated before completion.

Timeline

3 July 2019

Primary endpoint
27 May 2021

4 December 2023

Quick facts

Lead sponsor	National Institute of Mental Health (NIMH)
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	diagnostic
Enrollment	13
Start date	3 July 2019
Primary completion	27 May 2021
Estimated completion	4 December 2023
Sites	1 location across United States

Drugs / interventions tested

• 11C-ER176 — full drug profile →
• 11C-PIB — full drug profile →
• Positron Emission Tomography (PET) Scan

Conditions studied

• Dementia — all drugs for Dementia →

Sponsor

National Institute of Mental Health (NIMH)

Who can join

18 and older, any sex, with Dementia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Standard Uptake Value Ratio Compared to the Cerebellum (SUVR) Area Under the Curve (AUC) (60-90min) Primary · Up to 90 minutes during scan

Participants underwent brain positron emission tomography (PET) scan with \[11C\]ER176 and standard uptake value (SUV) was measured over 90 minutes and divided by SUV of the cerebellum to determine difference of \[11C\]ER176 brain uptake

Dorsolateral Prefrontal Cortex

Group	Value	95% CI
Healthy Volunteers	1.154816988	± 0.1068451736460
Subjects With Frontotemporal Dementia (FTD)	1.243023793	± 0.20560563
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	0.936561195	± 0.190544723

Dorsomedial Prefrontal Cortex

Group	Value	95% CI
Healthy Volunteers	0.996700383	± 0.071340712
Subjects With Frontotemporal Dementia (FTD)	0.989731836	± 0.093928709
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	0.905523672	± 0.048246962

Orbitofrontal Lobe

Group	Value	95% CI
Healthy Volunteers	1.217485758	± 0.088415727
Subjects With Frontotemporal Dementia (FTD)	1.267286508	± 0.045403115
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	1.047192088	± 0.146706043

Perisylvian Cortex, Left

Group	Value	95% CI
Healthy Volunteers	1.143352336	± 0.102185733
Subjects With Frontotemporal Dementia (FTD)	1.132367538	± 0.049940532
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	1.029305407	± 0.066022192

Perisylvian Cortex, Right

Group	Value	95% CI
Healthy Volunteers	1.090685411	± 0.071228603
Subjects With Frontotemporal Dementia (FTD)	1.112003017	± 0.09381086
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	0.941024006	± 0.055892402

Parietal Lobe, Left

Group	Value	95% CI
Healthy Volunteers	1.073048863	± 0.083878696
Subjects With Frontotemporal Dementia (FTD)	1.034142945	± 0.01253728
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	0.918176888	± 0.114668223

Parietal Lobe, Right

Group	Value	95% CI
Healthy Volunteers	1.020202657	± 0.069903326
Subjects With Frontotemporal Dementia (FTD)	1.031347183	± 0.03211946
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	0.848570905	± 0.190475917

Medial Temporal Lobe, Left

Group	Value	95% CI
Healthy Volunteers	1.08451324	± 0.07643309
Subjects With Frontotemporal Dementia (FTD)	1.064745227	± 0.093063402
Subjects With Chromosome 9 Open Reading Frame 72 (C9ORF72)	1.032603069	± 0.036960689

Sponsor's own description

Background:

Aging-related progressive neurological disorders include frontotemporal dementia, Lou Gehrig s disease, and Alzheimer s disease. Little is known about what causes these disorders. Brain inflammation may be involved. Researchers want to see if scans using radioactive drugs can show brain inflammation.

Objective:

To see if the drug \[11C\]ER176 can show inflammation in the brain in people with certain progressive neurological disorders compared to healthy adults. Also to find genes that might be associated with or cause these disorders.

Eligibility:

People ages 18 and older with an aging-related neurological disorder, and healthy adults

Design:

Participants will be screened with a medical history, physical exam, neurological exam, psychiatric history, and blood tests.

Participants will have 2-5 visits for the first session. They will have 2 PET scans and 1 MRI scan. They may have 3 more sessions: 6 months to about 18 months later, 1 year after that, and about 30 months to 5 years after the first visit. There may be up to 20 total visits.

For the scans, participants will lie on a bed that slides into the scanners. For the PET scans, a strap will fix their head in place. A radioactive drug will be injected through a catheter. A needle will guide a thin plastic tube into an arm vein. Additional catheters may be put in place to draw blood. Each PET will take 2 hours. The MRI will take 30 60 minutes.

At each session, participants will have a brief interview, medical history, physical exam, blood and urine tests, heart tests, and memory and thinking tests. They may donate blood for DNA tests.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Novel PET Imaging of Inflammatory Targets and Cells for the Diagnosis and Monitoring of Giant Cell Arteritis and Polymyalgia Rheumatica.
   van der Geest KSM, Sandovici M, Nienhuis PH, Slart RHJA, et al · · 2022 · cited 21× · PMID 35733858 · DOI 10.3389/fmed.2022.902155
2. Novel Tracers and Radionuclides in PET Imaging.
   Mason C, Gimblet GR, Lapi SE, Lewis JS. · · 2021 · cited 10× · PMID 34392925 · DOI 10.1016/j.rcl.2021.05.012