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Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

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ClinicalTrials.gov Identifier: NCT02834065
Recruitment Status : Recruiting
First Posted : July 15, 2016
Last Update Posted : July 9, 2019
Sponsor:
Collaborators:
Emory Healthcare
University of Pennsylvania
National Institutes of Health (NIH)
Baylor Scott & White
Information provided by (Responsible Party):
Duke University

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.

Condition or disease Intervention/treatment Phase
Cognition Disorders Device: Cardiopulmonary bypass machine Not Applicable

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 273 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
Actual Study Start Date : July 2016
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Deep Hypothermia
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature ≤20 degrees Celsius
Device: Cardiopulmonary bypass machine
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest

Active Comparator: Low Hypothermia
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 20.1 - 24.0 degrees Celsius
Device: Cardiopulmonary bypass machine
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest

Active Comparator: Moderate Hypothermia
Initiation of circulatory arrest using the cardiopulmonary bypass machine at temperature 24.1 - 28 degrees Celsius
Device: Cardiopulmonary bypass machine
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest




Primary Outcome Measures :
  1. Change in short-term cognition as measured by continuous cognitive score [ Time Frame: From baseline to 4 weeks post-operatively ]
    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 :
  1. 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 ]
  2. Change in long-term cognition as measured by continuous cognitive score [ Time Frame: From baseline to 1 year post-operatively ]
    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.

  3. Incidence of delirium [ Time Frame: Up to post-operative day 3 ]
    Confusion Assessment Method (CAM)

  4. Change in neurological function as measured by NIHSS [ Time Frame: Assessed at baseline, post-op day 4, 4 weeks ]
  5. Change in neuronal metabolism [ Time Frame: From baseline to 4 weeks ]
    Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate

  6. Change in resting-state functional connectivity [ Time Frame: From baseline to 4 weeks post-operatively ]
    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.

  7. Change in Duke Activity Status Index score [ Time Frame: From baseline to 4 weeks postoperatively ]
  8. Change in depression score [ Time Frame: From baseline to 4 weeks postoperatively ]
    Measured by the Center for Epidemiological Studies Depression Scale (CES-D).

  9. Change in anxiety score [ Time Frame: From baseline to 4 weeks postoperatively ]
    Measured by State Trait Anxiety Inventory (STA-I).

  10. Change in SF-36 score [ Time Frame: From baseline to 1 year postoperatively ]
  11. Change in employment status [ Time Frame: From baseline to 1 year postoperatively ]


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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). 14) patients who have received chemotherapy in the last 12 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02834065


Contacts
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Contact: Tiffany Bisanar, RN, BSN 919-681-0866 tiffany.bisanar@duke.edu
Contact: Bonita Bunk, RN 919-684-0861 bonita.funk@duke.edu

Locations
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United States, Georgia
Emory Saint Joseph's Hospital Recruiting
Atlanta, Georgia, United States, 30342
Contact: Michele Fielding, RN, BSN       mfield@emory.edu   
Principal Investigator: Edward P Chen, MD         
United States, North Carolina
Duke University Health System Recruiting
Durham, North Carolina, United States, 27710
United States, Pennsylvania
Penn Presbyterian Medical Center Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Marisa Konig, RN, MSN       marisa.konig@uphs.upenn.edu   
Principal Investigator: Wilson Y Szeto, MD         
United States, Texas
Baylor Scott & White Research Institute Recruiting
Plano, Texas, United States, 75093
Contact: Amanda Fenlon       amanda.fenlon@bswhealth.org   
Principal Investigator: Michael DiMaio, MD         
Principal Investigator: William Brinkman, MD         
Sponsors and Collaborators
Duke University
Emory Healthcare
University of Pennsylvania
National Institutes of Health (NIH)
Baylor Scott & White
Investigators
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Principal Investigator: Joseph P Mathew, MD, MHSc, MBA Duke University Health System

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Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT02834065     History of Changes
Other Study ID Numbers: Pro00064962
First Posted: July 15, 2016    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Duke University:
Postoperative Cognitive Decline
Deep Hypothermic Circulatory Arrest
Cardiovascular Surgical Procedures
Functional Magnetic Resonance Imaging
Small Ubiquitin-Related Modifier Proteins

Additional relevant MeSH terms:
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Cognition Disorders
Hypothermia
Neurocognitive Disorders
Mental Disorders
Body Temperature Changes
Signs and Symptoms