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Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

Primary Purpose

Cognition Disorders

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cardiopulmonary bypass machine
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cognition Disorders focused on measuring Postoperative Cognitive Decline, Deep Hypothermic Circulatory Arrest, Cardiovascular Surgical Procedures, Functional Magnetic Resonance Imaging, Small Ubiquitin-Related Modifier Proteins

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy

Exclusion Criteria:

  • < 18 years of age
  • History of symptomatic cerebrovascular disease, eg, prior stroke with residual deficit
  • Alcoholism (> 2 drinks/day)
  • Psychiatric illness (any clinical diagnoses requiring therapy)
  • Drug abuse (any illicit drug use in the past 3 months)
  • Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal)
  • Severe pulmonary insufficiency (requiring home oxygen therapy)
  • Renal failure (serum creatinine > 2.0 mg/dL)
  • Claustrophobic fear
  • Unable to read and thus unable to complete the cognitive testing
  • Pregnant women
  • Patients who score < 24 on a baseline Mini Mental State Examination (MMSE) or ≥ 27 on the baseline Center for Epidemiological Studies Depression (CES-D) scale
  • Patients who have pre-existing unsafe implants for 3 Tesla magnetic resonance imaging (MRI).
  • Patients who have received chemotherapy in the last 12 months.
  • Patients with COVID-19 diagnosis within the past 12 months

Sites / Locations

  • Emory Saint Joseph's Hospital
  • Duke University Health System
  • Penn Presbyterian Medical Center
  • Baylor Scott & White Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Deep Hypothermia

Low Hypothermia

Moderate Hypothermia

Arm Description

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius

Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius

Outcomes

Primary Outcome Measures

Change in short-term cognition as measured by continuous cognitive score
To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 4 weeks.

Secondary Outcome Measures

Change in SUMO 2/3 levels
Change in long-term cognition as measured by continuous cognitive score
To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 1 year.
Incidence of delirium
Confusion Assessment Method (CAM)
Change in neurological function as measured by NIHSS
Change in neuronal metabolism
Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate
Change in resting-state functional connectivity
For the rs-fMRI data, the analyses of primary interest will be the spontaneous, low-frequency fluctuations in the blood oxygen level dependent (BOLD) data of the Default Mode, Salience, and Executive Control Networks.
Change in Duke Activity Status Index score
Change in depression score
Measured by the Center for Epidemiological Studies Depression Scale (CES-D).
Change in anxiety score
Measured by State Trait Anxiety Inventory (STA-I).
Change in SF-36 score
Change in employment status

Full Information

First Posted
July 6, 2016
Last Updated
February 23, 2023
Sponsor
Duke University
Collaborators
Emory Healthcare, University of Pennsylvania, National Institutes of Health (NIH), Baylor Scott and White Health, National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT02834065
Brief Title
Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
Official Title
Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
July 28, 2016 (Actual)
Primary Completion Date
January 2022 (Actual)
Study Completion Date
February 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Emory Healthcare, University of Pennsylvania, National Institutes of Health (NIH), Baylor Scott and White Health, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
In this study the investigator will randomize 273 subjects to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during aortic arch surgery with circulatory arrest. The primary purpose of this study is to determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest in participants.
Detailed Description
Purpose of the Study: Determine the effect of deep vs low vs moderate hypothermia on neurocognitive function, brain functional connectivity, and leukocyte SUMOylation patterns after surgical circulatory arrest. Hypothesis: Deep hypothermia is superior to moderate hypothermia in reducing postoperative cognitive decline and preserving brain functional connectivity and that low hypothermia is non-inferior to deep hypothermia. Design and Procedures: 273 informed and consenting patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy will be randomized to deep (<20°C), low (20.1°C-24°C), or moderate (24.1°C-28°C) hypothermia during circulatory arrest. Cognitive testing using a standard battery will occur preoperatively (baseline), at 4 weeks, and at 1 year after surgery. Neuroimaging procedures before surgery, and at 4 weeks and 1 year after surgery will consist of high-resolution anatomic, resting-state fMRI (rs-fMRI) and magnetic resonance spectroscopy (MRS) sequences. To characterize leukocyte activation, whole blood will be drawn at 5 time points: at baseline (prior to surgery), before circulatory arrest, 10 minutes after reperfusion, 10 minutes after CPB, and 4 hours after CPB.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cognition Disorders
Keywords
Postoperative Cognitive Decline, Deep Hypothermic Circulatory Arrest, Cardiovascular Surgical Procedures, Functional Magnetic Resonance Imaging, Small Ubiquitin-Related Modifier Proteins

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
273 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Deep Hypothermia
Arm Type
Active Comparator
Arm Description
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius
Arm Title
Low Hypothermia
Arm Type
Active Comparator
Arm Description
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius
Arm Title
Moderate Hypothermia
Arm Type
Active Comparator
Arm Description
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius
Intervention Type
Device
Intervention Name(s)
Cardiopulmonary bypass machine
Intervention Description
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest
Primary Outcome Measure Information:
Title
Change in short-term cognition as measured by continuous cognitive score
Description
To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 4 weeks.
Time Frame
From baseline to 4 weeks post-operatively
Secondary Outcome Measure Information:
Title
Change in SUMO 2/3 levels
Time Frame
Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass
Title
Change in long-term cognition as measured by continuous cognitive score
Description
To characterize cognitive function over time while minimizing potential redundancy in the cognitive measures, a factor analysis will be performed on the cognitive test scores from baseline. A continuous change score will be calculated by subtracting the baseline cognitive index (the mean of the domain scores from factor analysis) from the follow-up cognitive index at 1 year.
Time Frame
From baseline to 1 year post-operatively
Title
Incidence of delirium
Description
Confusion Assessment Method (CAM)
Time Frame
Up to post-operative day 3
Title
Change in neurological function as measured by NIHSS
Time Frame
Assessed at baseline, post-op day 4, 4 weeks
Title
Change in neuronal metabolism
Description
Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate
Time Frame
From baseline to 4 weeks
Title
Change in resting-state functional connectivity
Description
For the rs-fMRI data, the analyses of primary interest will be the spontaneous, low-frequency fluctuations in the blood oxygen level dependent (BOLD) data of the Default Mode, Salience, and Executive Control Networks.
Time Frame
From baseline to 4 weeks post-operatively
Title
Change in Duke Activity Status Index score
Time Frame
From baseline to 4 weeks postoperatively
Title
Change in depression score
Description
Measured by the Center for Epidemiological Studies Depression Scale (CES-D).
Time Frame
From baseline to 4 weeks postoperatively
Title
Change in anxiety score
Description
Measured by State Trait Anxiety Inventory (STA-I).
Time Frame
From baseline to 4 weeks postoperatively
Title
Change in SF-36 score
Time Frame
From baseline to 1 year postoperatively
Title
Change in employment status
Time Frame
From baseline to 1 year postoperatively

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who are scheduled for elective proximal aortic reconstructive surgery (ascending aorta + aortic valve or root) with concomitant proximal hemi- or total arch replacement via median sternotomy Exclusion Criteria: < 18 years of age History of symptomatic cerebrovascular disease, eg, prior stroke with residual deficit Alcoholism (> 2 drinks/day) Psychiatric illness (any clinical diagnoses requiring therapy) Drug abuse (any illicit drug use in the past 3 months) Hepatic insufficiency (liver function tests > 1.5 times the upper limit of normal) Severe pulmonary insufficiency (requiring home oxygen therapy) Renal failure (serum creatinine > 2.0 mg/dL) Claustrophobic fear Unable to read and thus unable to complete the cognitive testing Pregnant women Patients who score < 24 on a baseline Mini Mental State Examination (MMSE) or ≥ 27 on the baseline Center for Epidemiological Studies Depression (CES-D) scale Patients who have pre-existing unsafe implants for 3 Tesla magnetic resonance imaging (MRI). Patients who have received chemotherapy in the last 12 months. Patients with COVID-19 diagnosis within the past 12 months
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joseph P Mathew, MD, MHSc, MBA
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Emory Saint Joseph's Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Penn Presbyterian Medical Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Baylor Scott & White Research Institute
City
Plano
State/Province
Texas
ZIP/Postal Code
75093
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

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