Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

Cognition Disorders Clinical Trial

Official title:

Cognitive Effects of Body Temperature During Hypothermic Circulatory Arrest

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02834065
• Other study ID #: Pro00064962
• Secondary ID: 1R01HL130443-01A
• Status: Completed
• Phase: N/A
• Start date: July 28, 2016
• Est. completion date: February 2023

Study information

• Verified date: February 2023
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: February 2023
• Est. primary completion date: January 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cognition Disorders
• Hypothermia

Intervention

Device:
• Cardiopulmonary bypass machine
Routinely used cardiopulmonary bypass machine (standard of care) will be used to initiate circulatory arrest

Locations

Country	Name	City	State
United States	Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Duke University Health System	Durham	North Carolina
United States	Penn Presbyterian Medical Center	Philadelphia	Pennsylvania
United States	Baylor Scott & White Research Institute	Plano	Texas

Sponsors (6)

Lead Sponsor	Collaborator
Duke University	Baylor Scott and White Health, Emory Healthcare, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	From baseline to 4 weeks post-operatively
Secondary	Change in SUMO 2/3 levels		Pre-incision, before circulatory arrest, 10 minutes after reperfusion, 10 minutes after cardiopulmonary bypass, 4 hrs after cardiopulmonary bypass
Secondary	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.	From baseline to 1 year post-operatively
Secondary	Incidence of delirium	Confusion Assessment Method (CAM)	Up to post-operative day 3
Secondary	Change in neurological function as measured by NIHSS		Assessed at baseline, post-op day 4, 4 weeks
Secondary	Change in neuronal metabolism	Magnetic resonance spectra (metabolic peaks) of myoinositol, creatine, choline and N-acetyl aspartate	From baseline to 4 weeks
Secondary	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.	From baseline to 4 weeks post-operatively
Secondary	Change in Duke Activity Status Index score		From baseline to 4 weeks postoperatively
Secondary	Change in depression score	Measured by the Center for Epidemiological Studies Depression Scale (CES-D).	From baseline to 4 weeks postoperatively
Secondary	Change in anxiety score	Measured by State Trait Anxiety Inventory (STA-I).	From baseline to 4 weeks postoperatively
Secondary	Change in SF-36 score		From baseline to 1 year postoperatively
Secondary	Change in employment status		From baseline to 1 year postoperatively