Clinical trial NCT02834065: Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
Official title: Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognition Disorders
Keywords: Postoperative Cognitive Decline
Deep Hypothermic Circulatory Arrest
Cardiovascular Surgical Procedures
Functional Magnetic Resonance Imaging
Small Ubiquitin-Related Modifier Proteins
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Emory Healthcare
name: University of Pennsylvania
name: National Institutes of Health (NIH)
name: Baylor Scott and White Health
name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2016-07-15
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in short-term cognition as measured by continuous cognitive score
timeFrame: From baseline to 4 weeks post-operatively
Secondary outcomes:
measure: Change in SUMO 2/3 levels
timeFrame: Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass
measure: Change in long-term cognition as measured by continuous cognitive score
timeFrame: From baseline to 1 year post-operatively
measure: Incidence of delirium
timeFrame: Up to post-operative day 3
measure: Change in neurological function as measured by NIHSS
timeFrame: Assessed at baseline, post-op day 4, 4 weeks
measure: Change in neuronal metabolism
timeFrame: From baseline to 4 weeks
measure: Change in resting-state functional connectivity
timeFrame: From baseline to 4 weeks post-operatively
measure: Change in Duke Activity Status Index score
timeFrame: From baseline to 4 weeks postoperatively
measure: Change in depression score
timeFrame: From baseline to 4 weeks postoperatively
measure: Change in anxiety score
timeFrame: From baseline to 4 weeks postoperatively
measure: Change in SF-36 score
timeFrame: From baseline to 1 year postoperatively
measure: Change in employment status
timeFrame: From baseline to 1 year postoperatively
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Saint Joseph's Hospital
state: Georgia
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
city: Philadelphia
country: United States
facility: Penn Presbyterian Medical Center
state: Pennsylvania
city: Plano
country: United States
facility: Baylor Scott & White Research Institute
state: Texas
Study officials:
affiliation: Duke Health
name: Joseph P Mathew, MD, MHSc, MBA
role: PRINCIPAL_INVESTIGATOR
References: