The Heart-Mind Connection: Evaluating the Association Between Ceramides and Cognitive Decline in Coronary Artery Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2014 by Sunnybrook Health Sciences Centre
Sponsor:
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT01625754
First received: May 24, 2012
Last updated: December 19, 2014
Last verified: December 2014
  Purpose

Many studies have shown that those with coronary artery disease (CAD) have a more rapid decline in memory than expected and that they are at an increased risk of developing dementia. It is not understood how memory decline is linked to CAD; however, it has recently been discovered that certain byproducts of fat breakdown involved in the development of CAD, called ceramides, can harm brain cells. In the present study the investigators will recruit 129 CAD patients from a cardiac rehabilitation facility and measure memory performance and blood ceramide concentrations at baseline, 3 months and 6 months. The investigators will also measure important blood messengers of inflammation and assess whether they are associated with ceramide production. In addition, relationships between ceramides and other aspects of brain function, such as thinking speed and the ability to plan and sort information will be explored.


Condition Intervention
Coronary Artery Disease
Behavioral: Exercise

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: The Heart-Mind Connection: Evaluating the Association Between Ceramides and Cognitive Decline in Coronary Artery Disease

Resource links provided by NLM:


Further study details as provided by Sunnybrook Health Sciences Centre:

Primary Outcome Measures:
  • Change in Verbal memory [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Verbal memory will be assessed using the California Verbal Learning Test, 2nd Edition (CVLT-II)


Secondary Outcome Measures:
  • Neuropsychiatric battery [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    The neuropsychiatric assessment battery recommended by NINDS-CSN harmonized standards will be conducted

  • Montreal Cognitive Assessment (MoCA) [ Time Frame: Baseline, 3 months, 6 months ] [ Designated as safety issue: No ]
    The MoCA will be used to assess global cognition


Biospecimen Retention:   Samples With DNA

Whole blood for ApoE4 genotyping


Estimated Enrollment: 129
Study Start Date: November 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Cardiac rehabilitation
This study recruits individuals that are currently participating in a cardiac rehabilitation exercise program.
Behavioral: Exercise
All individuals will be prescribed an exercise regimen according to their cardiac rehabilitation program

Detailed Description:

Coronary artery disease (CAD) affects about 19.8% of Canadians over the age of 65 and significantly affects quality of life. Of particular importance, cognitive impairment, ranging from cognitive complaints to vascular dementia, is frequently part of the clinical presentation of CAD. Our own prospective pilot data suggest that 22.5% of CAD patients attending cardiac rehabilitation (CR) have evidence of cognitive impairment with lower verbal memory performance, a marker of hippocampal function, predicting poorer CR outcomes. The pathophysiological mechanisms that may contribute to cognitive decline in those with CAD have not been fully elucidated.

Ceramides are metabolites of sphingomyelin, lipid species enriched in the outer leaflet of the plasma membrane and cell organelles of all tissues. Higher peripheral blood concentrations of ceramides have been associated with the development and progression of CAD. We propose to use a specific and sensitive electrospray ionization-tandem mass spectrometry (ESI-MS/MS) assay to measure concentrations of ceramide species from human plasma and elucidate the relationship between ceramides and the change in verbal memory performance over 6 months in 129 subjects with CAD undergoing CR.

We hypothesize that higher plasma concentrations of the long chain ceramide species C22:0 and C24:0 will be associated with decline in verbal memory performance and overall cognitive performance as assessed by a standardized battery of cognitive tests recommended for the investigation of vascular cognitive impairment. We also hypothesize that changes in the plasma concentration of TNF-α (tumor necrosis factor-alpha) will be associated with changes in plasma concentrations of C22:0 and C24:0 over 6 months.

This study aims to clarify the significance of a novel mechanism involving ceramides and the propagation of inflammatory signals from the periphery to the brain in mediating neurodegeneration associated with CAD.

  Eligibility

Ages Eligible for Study:   50 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients with coronary artery disease participating in a cardiac rehabilitation exercise program

Criteria

Inclusion Criteria:

  • 50-75 years of age
  • speak and understand English
  • evidence of CAD based on at least 1 of the following:
  • previous hospitalization for myocardial infarction
  • angiographic evidence of ≥ 50% blockage in ≥ 1 major coronary artery
  • a prior revascularization procedure
  • no recent (last 4 weeks) hospitalization for cardiac events such as acute myocardial infarction, unstable angina, congestive heart failure, ventricular arrhythmias, coronary revascularization, or Canadian Cardiovascular Society Class 4 angina

Exclusion Criteria:

  • Type I diabetes
  • hypothyroidism, Parkinson's disease, any diagnosis of dementia including Alzheimer's disease, inflammatory disease (irritable bowel syndrome, Crohn's, arthritis, etc.), Huntington's chorea, brain tumour, other conditions that may affect cognitive performance such as history of epilepsy, subdural hematoma, traumatic brain injury, and clinical stroke, progressive supranuclear paralysis, Killip Class III or IV states, multiple sclerosis, severely disrupted liver/ kidney/ lung function
  • use of hypnotics, antipsychotics, antidepressants, and anticholinergic medication
  • premorbid psychiatric diagnosis of schizophrenia or bipolar disorder
  • significant cognitive impairment (MMSE ≤ 24)
  • diagnosis of any current Axis I disorder other than depression, phobias or nicotine abuse/dependence
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625754

Contacts
Contact: Maisha Khan, BSc (416) 480-6100 ext 3185 mkhan@sri.utoronto.ca
Contact: Abby Li, MSc, CCRP (416) 480-6100 ext 3185 abby.li@sunnybrook.ca

Locations
Canada, Ontario
Toronto Rehabilitation Institute - Cardiac Rehab Recruiting
Toronto, Ontario, Canada, M4G 1R7
Contact: Paul Oh, MD         
Sponsors and Collaborators
Sunnybrook Health Sciences Centre
Investigators
Principal Investigator: Krista Lanctôt, PhD Sunnybrook Health Sciences Centre
Principal Investigator: Nathan Herrmann, MD Sunnybrook Health Sciences Centre
  More Information

No publications provided by Sunnybrook Health Sciences Centre

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT01625754     History of Changes
Other Study ID Numbers: 279-2011
Study First Received: May 24, 2012
Last Updated: December 19, 2014
Health Authority: Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee

Keywords provided by Sunnybrook Health Sciences Centre:
Ceramides
Lipids

Additional relevant MeSH terms:
Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Arterial Occlusive Diseases
Arteriosclerosis
Cardiovascular Diseases
Heart Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on July 28, 2015