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MIcroglial Colony Stimulating Factor-1 Receptor (CSF1R) in Alzheimer's Disease | Clinical Trials | Clareo Health

TERMINATEDPHASE1

MIcroglial Colony Stimulating Factor-1 Receptor (CSF1R) in Alzheimer's Disease

A Randomised, Placebo-controlled, Single-blind Study to Characterise the Biomarker Effects of the Colony Stimulating Factor-1 (CSF-1) Receptor Antagonist JNJ-40346527 in Participants With Mild Cognitive Impairment

NCT04121208•University of Oxford

View on ClinicalTrials.gov

Summary

A phase 1 randomised, placebo-controlled, single-blind study to characterise the biomarker effects of the CSF-1 receptor antagonist JNJ-40346527 in participants with mild cognitive impairment. A maximum of 54 participants will be recruited to the two part study. The first part of the study will identify whether it is possible to identify biomarkers that may be used in future studies with JNJ-40346527 and part 2 will investigate a minimal efficacious JNJ-40346527 dose.

Detailed Description

Alzheimer's disease (AD) is a slow, progressive disease that profoundly affects memory and everyday function. There are treatments available that can help manage symptoms, but at present there is no cure, and no treatment that is effective at slowing the progression of AD. AD can begin to cause brain damage decades before symptoms such as memory loss become apparent. The trial will investigate the effect of the drug JNJ-40346527 on CSF-1R (colony stimulating factor-1 receptor), which is a protein on the outside of cells present in the brain. CSF-1R is responsible for the regulation of various cells, including microglial cells. Recent research suggests that reducing numbers of these microglial cells may be beneficial in slowing the progression of Alzheimer's disease. The Investigators want to see how well JNJ-40346527 is able to block CSF-1R, and in turn suppress these microglial cells. The study is designed to investigate whether or not it is possible to identify changes in levels of proteins which interact with CSF-1R, and changes in the activity or number of affected microglial cells present in the brain. This evidence may provide useful "biomarkers", measures of change in the body, which the Investigators could track to see how the drug is working. These "biomarkers" could then be used in further larger studies to more thoroughly test the benefits of the drug JNJ-40346527. The present study is not designed to test whether or not this drug can slow the progression of Alzheimer's disease. If biomarkers are identified in the study, further studies will be designed to test whether JNJ-40346527 can slow or prevent the progression of Alzheimer's disease.

Eligibility

Age

50 - 99 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Any gender over and including 50 years old.
•Willing and able to provide informed consent.
•Clinical Dementia Rating (Scale) (CDR) Global Score = 0.5.
•Self and/or study partner report and impairment on objective cognitive tasks (performance on Hopkin's verbal learning task-revised (HVLT-R) - delay recall and/or free recall \> 1 standard deviation (SD) below mean for age/education level).
•Study Partner available, that spends at least 4 hours per week with the participant. The Study Partner must be willing and able to assist with the CDR interview, and will be provided with their own Information Sheet and Informed Consent form.
•Able to read and write in English and with minimum 7 years of formal education.
•Be considered eligible according to the following Tuberculosis (TB) screening criteria:
•1. Have no history of latent or active TB at screening. An exception is made for participants who have a history of latent TB (defined for the purpose of this study as having had a positive result from either the tuberculin skin test or the QuantiFERON-TB® Gold test prior to screening) and documentation of having completed an adequate treatment regimen for latent TB within 1 year prior to the first administration of study agent. Adequate treatment for latent TB is defined according to local country guidelines for immunocompromised patients. If no local guidelines for immunocompromised patients exist, United States (US) guidelines must be followed. It is the responsibility of the Investigator to verify the adequacy of previous anti-TB treatment and provide appropriate documentation.
•2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
•3. Have had no recent (within approximately 3 months) close contact with a person with active TB or if there has been such contact, have been evaluated by a physician specialising in TB and found not to have evidence of, or require treatment for latent TB.
+10 more criteria

Exclusion Criteria

•Research participants who fulfil diagnostic criteria for any type of dementia (e.g. Alzheimer Dementia, Frontotemporal Dementia (FTD), Diffuse Lewy Body Dementia (DLBD), Vascular Dementia (VAD), etc) CDR ≥1.
•Known carriers of a presenilin 1 (PSEN1), presenilin 2 (PSEN2) or Amyloid Precursor Protein (APP) mutation associated with Autosomal Dominant AD or any other neurodegenerative disease.
•Prohibited or restricted concomitant medication as detailed in Section 10.1.7.
•Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre-manifest Huntington's disease, multiple sclerosis, Parkinson's disease, Down syndrome, active alcohol/drug abuse or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder. To quantify abuse is to define this as history of drug or alcohol abuse according to Diagnostic and Statistical Manual of Mental Disorders (5th Edition) (DSM-V) criteria within 6 months before screening or positive test result for alcohol and/or drugs of abuse at screening/admission.
•History of latent or active infection of one of the following infectious diseases at screening: Listeria infection, Histoplasma, Coccidioides, Paracoccidioides, Pneumocystis, nontuberculous mycobacteria, Blastomyces, Aspergillus, cytomegalovirus generalised or Herpes zoster infection
•Any cancer or history of cancer in the preceding 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
•Any conditions that are clinically significant and may deem the participant's participation in an investigational trial unsafe, e.g., symptomatic cardiovascular disease (including re-vascularisation procedures within the previous year), severe renal or hepatic failure, any clinically relevant abnormalities in blood parameters included in local routine assessments, severe loss of vision, hearing or communicative ability, conditions preventing co-operation or completing the required assessments in the trial, as judged by the Investigator.
•Any contraindications for Lumbar Puncture.
•Any evidence of intracranial pathology which may affect cognition including but not limited to brain tumours (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), history of or recovering haemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Research participants with an MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.
•Participation in a clinical trial with an Investigational Medicinal Product (IMP) in the last 30 days or 90 days in case of biologics.
+2 more criteria

Locations (3)

Cambridgeshire and Peterborough NHS Foundation Trust

Cambridge, United Kingdom

South London and Maudsley Hospital NHS Foundation Trust

London, United Kingdom

Oxford Health NHS Trust

Oxford, United Kingdom

Key Dates

Start Date

April 7, 2021

Primary Completion Date

February 18, 2022

Completion Date

February 18, 2022

Last Updated

May 9, 2024

Enrollment

ACTUAL participants

Conditions

Alzheimer DiseaseMild Cognitive Impairment

Interventions

JNJ-40346527

DRUG

Placebo

OTHER

Sense4Safety Intervention

NCT07220668

Mild Cognitive Impairment

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RECRUITINGEARLY_PHASE1

Psilocybin for Depression in People With Mild Cognitive Impairment or Early Alzheimer's Disease

NCT04123314

Depressive SymptomsDepression+2 more

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RECRUITING

Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: May 9, 2024Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

MIcroglial Colony Stimulating Factor-1 Receptor (CSF1R) in Alzheimer's Disease

Inclusion Criteria

Exclusion Criteria

Sense4Safety Intervention

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