Treating Depression in Coronary Artery Disease With Omega-3 Fatty Acids

NCT00981383 | Completed Phase 3 DMC

• 1 other identifier: CAROTID-2009
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

Depressive disorders are common in patients with Coronary Artery Disease (CAD), occurring in up to 47% of patients. Left untreated, these symptoms not only have a strong negative impact on quality-of-life, but also increase risk of future cardiac events and death. Unfortunately, about 64% of CAD patients do not respond to current antidepressant treatments. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are two omega-3 (ω-3) fatty acids found in fatty fish that are important for brain function. Recent evidence showed that depressed CAD patients have lower levels of EPA and DHA than non-depressed CAD patients. This information, taken together with the known roles of ω-3 fatty acids in brain function, suggests that deficiencies may contribute to depression. However, it is unknown if increasing consumption of ω-3 fatty acids would alleviate depression and improve quality of life. While intake of adequate levels of ω-3 fatty acids is difficult to obtain through diet, concentrated supplements containing EPA and DHA that are safe, readily available, and inexpensive are now obtainable in Canada. CAROTID (CAD Randomized Omega-3 Trial In Depression) will randomize patients with CAD, with and without depressive symptoms, after 6 months of cardiac rehabilitation and usual care to receive either ω-3 fatty acid supplements or placebo daily during their final 6 months of cardiac rehabilitation. The investigators hypothesize that CAD patients randomized to receive ω-3 fatty acid supplements will show greater improvement in depressive symptoms and quality-of-life over time. The investigators will also evaluate possible improvements in other important determinants of quality of life: memory and other cognitive abilities.

Conditions

Coronary Artery Disease; Depression

Keywords

Fatty Acids, Omega-3

Outcome Measures

Primary Outcomes (1)

• Hamilton Rating Scale of Depression (HAM-D)

  Baseline, Week 4, Week 8, Week 12

Secondary Outcomes (2)

• Medical Outcomes Study health survey 36-item Short Form (SF-36)

  Baseline, Week 4, Week 8, Week 12

• Beck Depression Inventory-II (BDI-II)

  Baseline, Week 4, Week 8, Week 12

Study Arms (2)

Treatment

EXPERIMENTAL

Omega-3 Fatty Acid Supplement, 1.9 g ω-3 FAs daily

Dietary Supplement: Omega-3 Fatty Acid Supplement

Placebo

PLACEBO COMPARATOR

Matching placebo, less than 0.12 g ω-3 FAs daily

Other: Placebo

Interventions

Omega-3 Fatty Acid Supplement DIETARY_SUPPLEMENT

3 capsules (3x1g) fish oil-derived concentrated ethyl esters, providing 1.9 g omega-3 fatty acids (1.2 g EPA and 0.6 g DHA, with 0.1 g other omega-3 fatty acids)

Treatment

Placebo OTHER

3 capsules (3x1g) of 50/50 soybean/corn oil blend containing less than 0.12 g of omega-3 fatty acids with negligible EPA and DHA

Placebo

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Language (speaks and understands English)
• Between 45-80 years old
• Stable coronary artery disease (based on no hospitalization for cardiac events for at least 7 weeks prior)
• Angiographic documentation of presence and extent of coronary artery disease (number of vessels involved, extent of stenosis, etc.)
• Written, informed consent

You may not qualify if:

• Significant acute medical illness (sepsis, autoimmune condition, drug overdose, uncontrolled diabetes, severely disturbed liver, kidney or lung function, anemia, hypothyroidism)
• Clinically significant cognitive impairment (Mini-Mental State Examination \< 24)
• Other neurologic conditions (Parkinson's disease, Huntington's chorea, history of epilepsy, birth trauma, significant traumatic brain injury, clinical stroke, progressive supranuclear paralysis, brain tumour, subdural hematoma, multiple sclerosis)
• Canadian Cardiovascular Society Class 4 (indicating unstable angina)
• Ventricular tachycardia and/or implantable cardioverter defibrillator
• Killip class greater than II (indicates high risk of mortality in post-myocardial infarction group)
• Premorbid or concurrent psychiatric diagnoses of schizophreniform or bipolar depressive disorders, current ethanol or substance abuse or any premorbid psychiatric condition requiring hospitalization
• Current use of a concentrated omega-3 fatty acid supplement, or contraindication to soybean/corn oil
• Pregnant women
• Women who become pregnant during the course of the study will be excluded immediately.
• Women of childbearing potential must be using an approved method of birth control.
• Allergies or hypersensitivity to fish
• Pre-existing bleeding disorder
• History of electroconvulsive therapy.
• Suicidal ideation or a history of suicidal ideation/attempts (determined during SCID-I at screening/baseline visits)

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Toronto Rehabilitation Institute: collaborator

Study Sites (2)

Toronto Rehabilitation Institute

Toronto, Ontario, M4G 1R7, Canada

Location

Trillium Health Centre - West Toronto

Toronto, Ontario, M9C1A5, Canada

Location

Related Publications (3)

• Mazereeuw G, Herrmann N, Oh PI, Ma DW, Wang CT, Kiss A, Lanctot KL. Omega-3 Fatty Acids, Depressive Symptoms, and Cognitive Performance in Patients With Coronary Artery Disease: Analyses From a Randomized, Double-Blind, Placebo-Controlled Trial. J Clin Psychopharmacol. 2016 Oct;36(5):436-44. doi: 10.1097/JCP.0000000000000565.

  PMID: 27529771 RESULT

• Chan P, Suridjan I, Mohammad D, Herrmann N, Mazereeuw G, Hillyer LM, Ma DWL, Oh PI, Lanctot KL. Novel Phospholipid Signature of Depressive Symptoms in Patients With Coronary Artery Disease. J Am Heart Assoc. 2018 May 5;7(10):e008278. doi: 10.1161/JAHA.117.008278.

  PMID: 29730646 DERIVED

• Mazereeuw G, Herrmann N, Xu H, Blanchard AP, Figeys D, Oh PI, Bennett SA, Lanctot KL. Platelet activating factors are associated with depressive symptoms in coronary artery disease patients: a hypothesis-generating study. Neuropsychiatr Dis Treat. 2015 Sep 4;11:2309-14. doi: 10.2147/NDT.S87111. eCollection 2015.

  PMID: 26379437 DERIVED

MeSH Terms

Conditions

Coronary Artery Disease; Depression

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Behavioral Symptoms; Behavior

Study Officials

• Krista Lanctôt, PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

• Nathan Herrmann, MD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 10, 2009
• First Posted: September 22, 2009
• Study Start: June 1, 2010
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2016
• Last Updated: April 28, 2017

Record last verified: 2017-04

Locations

CA (2)