Taking Brain Monitoring to the Next Level (HDBRAIN)

• ClinicalTrials.gov Identifier: NCT04246320
• Recruitment Status: Completed
• First Posted: January 29, 2020
• Last Update Posted: January 19, 2023
• Sponsor: University of California, Los Angeles
• Information provided by (Responsible Party): Rajesh Kumar, PhD, University of California, Los Angeles

Tracking Information

• First Submitted Date: January 23, 2020
• First Posted Date: January 29, 2020
• Last Update Posted Date: January 19, 2023
• Actual Study Start Date: January 30, 2020
• Actual Primary Completion Date: August 13, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 27, 2020)

• Postoperative cognitive dysfunction [ Time Frame: Preoperatively (within 15 days of surgery) ]
  Montreal Cognitive Assessment (MoCA) test
• Postoperative cognitive dysfunction [ Time Frame: postoperatively at discharge (within 2 weeks of surgery). ]
  Montreal Cognitive Assessment (MoCA) test
• Postoperative cognitive dysfunction [ Time Frame: 6 months after surgery. ]
  Montreal Cognitive Assessment (MoCA) test
• Postoperative Delirium [ Time Frame: Daily for up to 3 days postoperatively ]
  Confusion Assessment Method (CAM-ICU)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: May 16, 2022)

• Examining brain changes [ Time Frame: Typically less than 15 days before surgery, when the patient comes for the preoperative evaluation, postoperatively at up to 48 hours after surgery, and 6 months post surgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Examining brain changes II [ Time Frame: postoperatively within 2 weeks of surgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Examining brain changes III [ Time Frame: 6 months post surgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Blood anti-inflammatory biomarkers [ Time Frame: pre-operatively (within 15 days before surgery) ]
  Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects
• Blood anti-inflammatory biomarkers [ Time Frame: post-operatively (within 2 days of surgery) ]
  Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects

Original Secondary Outcome Measures (submitted: January 27, 2020)

• Examining brain changes [ Time Frame: Typically less than 15 days before surgery, when the patient comes for the preoperative evaluation, postoperatively at up to 48 hours after surgery, and 6 months post surgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Examining brain changes II [ Time Frame: postoperatively within 2 weeks ofsurgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Examining brain changes III [ Time Frame: 6 months post surgery ]
  Using non-invasive magnetic resonance imaging based diffusion tensor imaging
• Blood anti-inflammatory biomarkers [ Time Frame: pre-operatively (within 15 days before surgery) ]
  Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects
• Blood anti-inflammatory biomarkers [ Time Frame: post-operatively (within 2 days of surgery) ]
  Assess blood inflammatory biomarkers (Il6, Il10, TNFa, IL1b, HMGB1) in OSA subjects and non-OSA subjects

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Taking Brain Monitoring to the Next Level
• Official Title: Taking Brain Monitoring to the Next Level
• Brief Summary: This one arm clinical study will assess the impact of a goal directed therapy intervention, aiming at optimizing depth of anesthesia and intraoperative blood pressure on the incidence of postoperative cognitive dysfunction and delirium relative to a standardized anesthetic plan. We will enroll 60 patients and will measure the neurocognitive status (MoCA test) of patients before and after surgery (at discharge, within 2 weeks after surgery and 6 months after surgery) to determine the relative impact of anesthetic care on the development of postoperative delirium and cognitive decline. All patients will have a brain scan (fMRI) before and after surgical intervention. Patients will also be asked to participate in an optional blood draw which will take place during their brain imaging visit and post operatively (within 2 days after surgery).

Detailed Description

This study will test the hypothesis that a goal directed therapy intervention, which optimizes depth of anesthesia and intraoperative blood pressure can decrease the incidence of postoperative neurocognitive dysfunction

Subjects will be recruited for the study and the protocol explained. In addition to standard American Society of Anesthesiologists (ASA) monitoring, we will monitor continuous non-invasive blood pressure and 4 lead electroencephalogram (EEG) channels. Patients will receive standardized anesthesia care in addition to a goal directed therapy hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).

Neurocognitive testing: In order to assess general cognitive function, the Montreal Cognitive Assessment test will be used. Cognitive function will be measured preoperatively and postoperatively at discharge, 1 month and 6 months after surgery. For delirium measurement, we will administer daily the Confusion Assessment Method (CAM-ICU) for up to 3 days.

The Montreal Cognitive Assessment (MoCA) is a screening tool to assess mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, visuoconstructionals skills, conceptual thinking, calculations, and orientation. Time to administer the MoCA is approximately 10 minutes. The total possible score is 30 points; a score of 26 or above is considered normal.

The Wide Range Assessment of Memory and Learning (WRAML2) is a broad-based memory battery that provides a flexible measure of memory functioning and learning and takes approximately 45-60 minutes to administer. This assessment will be conducted at the first MRI visit and at the 6 month follow up.

The Confusion Assessment Method for the ICU (CAM-ICU) screens for the development of delirium and assesses four features: 1) acute change or fluctuation in mental status from baseline, 2) inattention, 3) altered level of consciousness, and 4) disorganized thinking. The CAM-ICU is positive, and the patient is considered to have delirium, if features 1 and 2 and either feature 3 or 4 are present.

Brain imaging: The timing of pre-operative brain imaging will be as allowed by patient factors and scanner availability, typically less than 15 days before surgery, when the patient comes for the preoperative evaluation, and postoperatively within 2 weeks after surgery.

Optional Blood Draws: Patients will be asked to provide 2 optional blood samples, drawn the day of their brain imaging visit and post-operatively (within 2 days). These samples will be used to asses blood inflammatory biomarkers in obstructive sleep apnea (OSA) subjects and non-OSA subjects between baseline and post-surgery.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention

Condition

• Postoperative Cognitive Dysfunction
• Postoperative Delirium
• Obstructive Sleep Apnea

Intervention

Other: Goal directed therapy (GDT)

Goal directed therapy (GDT) hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).

Study Arms

Experimental: Intervention

Patients monitored and receiving a standard anesthesia plan in addition of a goal directed therapy (GDT) hemodynamic management (MAP > 60 mmHg) and processed EEG-guided anesthesia (PSI targeted between 30-50).

Intervention: Other: Goal directed therapy (GDT)

Publications *

• Joosten A, Rinehart J, Bardaji A, Van der Linden P, Jame V, Van Obbergh L, Alexander B, Cannesson M, Vacas S, Liu N, Slama H, Barvais L. Anesthetic Management Using Multiple Closed-loop Systems and Delayed Neurocognitive Recovery: A Randomized Controlled Trial. Anesthesiology. 2020 Feb;132(2):253-266. doi: 10.1097/ALN.0000000000003014.
• Vacas S, Cannesson M. Noninvasive Monitoring and Potential for Patient Outcome. J Cardiothorac Vasc Anesth. 2019 Aug;33 Suppl 1(Suppl 1):S76-S83. doi: 10.1053/j.jvca.2019.03.045. No abstract available.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 17, 2023): 7
• Original Estimated Enrollment (submitted: January 27, 2020): 60
• Actual Study Completion Date: August 13, 2022
• Actual Primary Completion Date: August 13, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 45-75 years old,
• undergoing abdominal, orthopedic, gynecological, or urological surgery
• expected to stay in hospital for at least 24hours

Exclusion Criteria:

• Substantial hearing impairment or inability to understand English, since there needs to be neurocognitive testing done
• status post craniotomy
• severe dementia

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 45 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04246320
• Other Study ID Numbers: HDBRAIN 16-001040
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rajesh Kumar, PhD, University of California, Los Angeles
• Original Responsible Party: Susana Vacas, MD, PhD, University of California, Los Angeles, Assistant Professor-in-Residence
• Current Study Sponsor: University of California, Los Angeles
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Rajesh Kumar, PhD; University of California, Los Angeles
• Principal Investigator: Susana Vacas, M.D., Ph.D.; Massachusetts General Hospital

• PRS Account: University of California, Los Angeles
• Verification Date: January 2023