Effect of Raised CBF During CEA on Cognition in DM Patients

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine if we can reduce the incidence of cognitive dysfunction - difficulty in performing certain pencil-paper, memory, finger dexterity and thinking type of tasks called neuropsychometric tests - in patients with adult onset diabetes mellitus (DM) undergoing surgery on the carotid artery (CEA). We hypothesize that cognitive dysfunction can be decreased in patients with type II DM by augmenting cerebral blood flow with a shunt during carotid endarterectomy compared to patients with Type II DM who are treated with conventional management in which a shunt is placed only if the electroencephalogram (EEG) indicates cerebral ischemia.

Detailed Description
-----------------
Based on previous clinical studies, we have found that patients with diabetes mellitus (DM) who are having carotid endarterectomy (CEA) have a four-fold higher incidence of cognitive dysfunction, 1 day and 1 month after surgery, than a control group of elderly diabetic patients having spine surgery. We hypothesize that this increased incidence is due to sub-cortical ischemia associated with the clamping of the ipsilateral carotid artery, because intra-operatively we rarely see EEG changes, or a significant number of emboli upon clamping or unclamping the carotid artery, or new cortical lesions of ischemia by MRI after surgery. In order to decrease cognitive dysfunction in patients with DM, we propose to randomize them to either i) have a shunt placed across the surgical site assuming it is surgically feasible or ii) be treated by conventional management during which time a shunt is placed only in the unlikely event of significant cortical ischemia determined by EEG, which occurs in about 5% of all cases. The purpose of this study is to determine if patients with adult-onset diabetes mellitus having the surgical procedure called carotid endarterectomy benefit from increasing blood flow to the brain with a shunt. A shunt is a tube inserted below and above the surgical area at the time when the carotid artery is clamped to allow the surgeon to work in a bloodless field and to supplement blood flow to the brain. Benefit is measured after surgery by comparing performance on a battery of cognitive tests, which test your ability to perform pencil-paper, memory and finger dexterity tests, to performance before surgery. Patients in the shunt group whom the surgeon at the time of surgical exposure considers too technically difficult to shunt, will not have a shunt inserted but will be treated statistically as if they were shunted (intention to treat). Follow-up evaluations will be performed 1 day, and 1 and 6 months after surgery so that the long-term effect of shunting can be evaluated. Cerebral injury will be determined in two ways. First, all patients will be evaluated using a battery of neuropsychometric tests before and after surgery. Patients admitted to the Irving Clinical Research Center (CRC) will have their tests 1 day before, and 1 day, and 1 and 6 months after surgery. Those coming into the hospital on the day of surgery, Same Day, will be evaluated on the day of surgery. They will be evaluated 1 day, and 1 and 6 months after surgery. Preoperative neurological and neuropsychological evaluation will be performed. The neuropsychometric tests are not intended to be diagnostic of specific neuropsychiatric disorders, but rather are designed to demonstrate general neuropsychological pathology. These tests can be divided into four types: (1) an evaluation of language, (2) an evaluation of speed of mental processing, (3) an evaluation of ability to learn using a list of words, and (4) an evaluation of visual perception requiring a patient to copy a complex figure. Before the battery is administered we will assess each patient's level of pain while sitting and standing using a 10 point Visual Analog Scale and gauge their mood with a series called the Wong/Baker Faces Rating scale. Patients having spine surgery may have significant pain before surgery which might impair their performance. We will also be measuring Quality of Life (QOL) in all enrolled patients. This will be done using two well-known examinations (Telephone Interview for Cognitive Status (TICS) and Centers for Disease Control and Prevention Health-Related Quality-of-Life 14Item Measure (CDC HRQOL14)) and a series of questions investigating how well patients are able to perform activities of daily living (ADLs) and instrumental activities of daily living (IADLs). These tests will be given at two time points, once before the surgery and then one month after surgery. We will look for changes in quality of life that may correlate with neuropsychometric test performance. Second, peripheral serum samples will be drawn before induction, before crossclamping the carotid artery, 15 minutes after crossclamping the carotid artery and 24 hours after surgery. Since the purpose of this study is to determine if a change in conventional management will improve patient's ability to perform our battery of neuropsychometric tests, we will randomly assign patients to either receive a shunt prophylactically if the surgeon determines that it is technically safe, even if conventional management does not indicate its necessary, or a shunt only if it is indicated by EEG, conventional management. Subjects in the prophylactic group will receive a shunt even when by standard criteria they would not need to receive one. Randomization will be performed in blocks of four patients each using a randomization table. Using block randomization we will increase the probability of an equal number of patients shunted or not shunted. The surgeon will be told which group the patient has been randomized into after induction and prior to clamping the carotid artery.

Official Title
-----------------
Effect of Augmentation of Cerebral Blood Flow on Neuropsychometric Performance After Carotid Endarterectomy in Type II Diabetic Patients

Conditions
-----------------
Carotid Artery Disease, Carotid Artery Stenosis, Diabetes, Cognitive Dysfunction

Intervention / Treatment
-----------------
* Procedure: Carotid endarterectomy
* Device: Shunt


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ability to speak English no history of permanent neurological impairment, Axis I psychiatric diagnosis or drug abuse scheduled for elective carotid endarterectomy for treatment of carotid artery stenosis diagnosed with diabetes mellitus or HbA1c value greater than 10% Exclusion Criteria: younger than 18 yrs

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional Shunt<br>Patients with diabetes mellitus (DM) undergoing carotid endarterectomy will receive a shunt only if it is indicated by EEG, by conventional management. | Procedure: Carotid endarterectomy<br>* When a shunt is inserted to increase blood flow to the brain<br>Device: Shunt<br>* A tube inserted below and above the surgical area at the time when the carotid artery is clamped to allow the surgeon to work in a bloodless field and to supplement blood flow to the brain.<br>|
| Experimental: Prophylactic Shunt<br>Patients with diabetes mellitus (DM) undergoing carotid endarterectomy will receive a shunt even when by standard criteria they would not need to receive one. | Procedure: Carotid endarterectomy<br>* When a shunt is inserted to increase blood flow to the brain<br>Device: Shunt<br>* A tube inserted below and above the surgical area at the time when the carotid artery is clamped to allow the surgeon to work in a bloodless field and to supplement blood flow to the brain.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Improved Neuropsychometric Changes | Battery of neuropsychometric tests to evaluate a variety of cognitive functions. | Post-operatively at 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Carotid Endarterectomy, Neuropsychological tests, Stroke, Transient ischemia, Hypoperfusion, Ischemia