Modulating ApoE Signalling to Reduce Brain Inflammation, deLirium and postopErative Cognitive Dysfunction

Last updated on July 2021

Recruitment

Recruitment Status: Recruiting
Estimated Enrollment: Same as current

Summary

Conditions

Postoperative Cognitive Dysfunction
Postoperative Delirium

Type

Interventional

Phase

Phase 2

Design

Allocation: RandomizedIntervention Model: Parallel AssignmentIntervention Model Description: Investigators will enroll 201 patients total in this phase 2 escalating dose study, with escalating CN-105 doses occurring in three successive groups of 67 patients each. In each group of 67 patients, 50 will receive a given dose of CN-105 and 17 will receive placebo.Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Masking Description: Participants will be randomized to receive either CN-105 or placebo after they consent to participate in the trial. Participants will be enrolled in 1 of 3 dose cohorts of 67 subjects each. An independent statistician will prepare dose stratified mixed block size randomization lists in a 3 to 1 ratio to achieve the desired distribution of drug and placebo. In each block of 67 trial participants, 50 will receive CN-105 and 17 will receive placebo, in a double-blind fashion. CN-105 and placebo will be prepared in identical bags labelled simply with the trial participant's number (1-201) to keep all trial staff and clinicians blinded to randomization. Only the investigational pharmacist will have the randomization list for each participant showing what dose of CN-105 or placebo will be administered. To minimize bias, investigators conducting the laboratory assays on the CSF and blood samples will be blinded to trial group assignment during the course of the trial.Primary Purpose: Prevention

Participation Requirements

Age: Between 60 years and 125 years
Gender: Both males and females

Description

This research study will evaluate the effectiveness and estimate the feasibility of administering an investigational drug called 'CN-105' (the study drug), to prevent postoperative cognitive decline, delirium (serious confusion) and underlying brain inflammatory and brain activity changes in adults 60 years and older undergoing surgery. The word "investigational" means the study drug is still being tested in research studies and is not approved by the U.S. Food and Drug Administration (FDA). It is hoped that CN-105 will block signaling via a gene known as ApoE4, the most common gene implicated in late life Alzheimer's disease. Depending on when patients enroll in this study, participants will receive either a placebo or a progressively higher dose of CN-105 until the safest and best tolerated dose is reached. The study drug is given via IV (intravenous, meaning through a vein) infusion in the hospital. Study drug infusions will be given up to 4 days after surgery. Participants will also perform memory and thinking tests, as well as complete a survey and functional assessments, both prior to surgery and again 6 weeks after surgery. Each of those research visits will last about 1 hour. Additionally, the investigators will collect a blood sample and a cerebrospinal fluid (CSF) sample prior to the participant's surgery, 24 hours after surgery, and again 6 weeks after surgery. To obtain the CSF (cerebrospinal fluid) sample, investigators will perform a lumbar (the lower part of the spinal column) puncture. During surgery, investigators will also record participant brain waves from the scalp using an EEG (electroencephalography) monitor. An electroencephalography monitor reads the electrical activity of the brain in different places using a cap with sensors that is worn on the head. Although previous studies have not found any associations between the study drug and any serious medical problems, investigators will monitor its effect on wound healing and postoperative infections. Benefits of this study include the possibility of fewer problems in thinking and memory after surgery if this study drug works as hoped. Risks of participation in this study include headache, infection/discomfort from the lumbar puncture, discomfort from the blood draw, and minor skin irritation or redness from the EEG and heart rate monitor procedures.

Tracking Information

NCT #: NCT03802396
Collaborators: Not Provided
Investigators: Principal Investigator: Miles Berger, MD, PhD Duke University