OCEAN: Omega 3 for Treatment of Depression in Patients With Heart Failure

• Sponsor: Wei Jiang (Other)
• Overall Status: Completed
• CT.gov ID: NCT02057406
• Collaborator: National Institute of Mental Health (NIMH) (NIH)
• Enrollment: 108
• Locations: 3
• Arms: 3
• Actual Duration (Months): 31.1
• Patients Per Site: 36
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Omega 3 supplements will improve depressive symptoms to a greater extent than placebo in heart failure patients with moderate to severe major depressive disorder.

Condition or Disease	Intervention/Treatment	Phase
Depression	Drug: 2:1 EPA/DHA; Drug: High EPA; Other: Placebo	Phase 3

Detailed Description

The primary objective of this study is to determine whether (Hypothesis 1a) and how (Hypothesis 1b) the two omega 3 supplements will reduce depressive symptoms in heart failure (HF) patients with moderate-to-severe major depressive disorder (MDD).

Hypothesis 1a: Omega 3 supplements will improve depressive symptoms to a greater extent than placebo; Hypothesis 1b: Pure eicosapentaenoic acid (EPA) will be superior to the EPA: docosahexaenoic acid (DHA) 2:1 in depression improvement.

Study Design

• Study Type: Interventional
• Actual Enrollment: 108 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Omega 3 for Comorbid Depression and Heart Failure Treatment
• Actual Study Start Date: May 1, 2014
• Actual Primary Completion Date: May 19, 2016
• Actual Study Completion Date: Dec 2, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 2:1 EPA/DHA 400/200 EPA/DHA fish oil 2 grams	Drug: 2:1 EPA/DHA; 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams; Other Names: 400 EPA/200 DHA 2 grams
Active Comparator: High EPA Almost pure EPA 2 grams	Drug: High EPA; Other Names: An almost pure Eicosapentaenoic acid 2 grams
Placebo Comparator: Placebo Matched placebo corn oil capsules	Other: Placebo; Other Names: Matched placebo corn oil capsules

Outcome Measures

Primary Outcome Measures

1. Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores. [Week 12]

   Endpoint HAMD scores are mean values adjusted for age, race, sex, treatment site, and the baseline HAMD value. The range for the HAMD scores is 0 to 52 with higher scores indicating a greater severity of depressive symptoms.

2. Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values. [Week 12]

   Endpoint EPA values are mean values adjusted for age, race, sex, treatment site, and the baseline EPA value. Red blood cell/plasma EPA values are expressed as a percent of total identified fatty acids.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult male and female patients, age greater than or equal to 21 years

• Diagnosis of Major Depressive Disorder determined by the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria with a Hamilton Depression Rating Scale Score greater than or equal to 18*

• New York Heart Association Class greater than or equal to II

• For patients with with left ventricular ejection fraction greater than 40 %, abnormal brain natriuretic peptide and/or previous hospitalization due to heart failure is also required

• For inpatients, the Hamilton Depression Rating Scale scores need to be remain at 18 or above for two weeks following the discharge

Exclusion Criteria:

• Significant cognitive impairment, indicated as a Mini-Mental State Examination (MMSE) total score of 23 or lower

• History of alcohol or other drug dependence within the past 90 days

• Severe physical disability (visual, sensory, or motor) that may interfere with psychiatric assessment

• History or presence of psychoses, bipolar disorder, and/or severe personality disorders

• Life-threatening comorbidity with the likelihood of 50% mortality in one year

• Active suicidal ideations

• Current use of antipsychotic medications or psychotropic medications except Selective Serotonin Reuptake Inhibitors (SSRIs) and /or benzodiazepine

• Female patients who have a positive pregnancy test or are lactating. If female patients are of childbearing potential, they must use an effective and accepted means of contraception, such as oral contraceptives or a double-barrier method (condom and diaphragm) to protect against pregnancy

• Documented history of hypersensitivity or intolerance to omega 3 products; or use of omega 3 supplement for greater than or equal to 3 months at an equivalent or greater dose of the proposed study

• Treatment with electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within 90 days*

• Uncorrected hypothyroidism or hyperthyroidism

• Treatment with any investigational agent within 1 month before randomization

• Acute coronary syndrome, i.e., Myocardial Infarction (MI) or unstable angina, revascularization procedure within the preceding month, or planned cardiac surgery within 3 months postrandomization

• The exclusion of patients who received ECT or TMS within 90 days is adopted from other depression-intervention trials and meant to eliminate confounders. It is believed that the effects of ECT on mood and cognition may last for a couple of months, and duration of TMS effects is poorly known and may be similar to the ECT intervention.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27514
2	Duke University Medical Center	Durham	North Carolina	United States	27710
3	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Wei Jiang
• National Institute of Mental Health (NIMH)

Investigators

• Principal Investigator: Wei Jiang, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wei Jiang, Professor, Duke University
• ClinicalTrials.gov Identifier: NCT02057406
• Other Study ID Numbers: Pro00043654; R34MH097034-01A1
• First Posted: Feb 7, 2014
• Last Update Posted: May 14, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Heart Failure; Depression; Depressive Disorder

Study Results

Participant Flow

Arm/Group Title	2:1 EPA/DHA	High EPA	Placebo
Arm/Group Description	400/200 EPA/DHA fish oil 2 grams 2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid (DHA) fish oil 2 grams	Almost pure EPA 2 grams High EPA	Matched placebo corn oil capsules Placebo
Period Title: Overall Study
STARTED	36	36	36
COMPLETED	35	33	32
NOT COMPLETED	1	3	4

Baseline Characteristics

Arm/Group Title	2:1 EPA/DHA	High EPA	Placebo	Total
Arm/Group Description	400/200 EPA/DHA fish oil 2 grams 2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams	Almost pure EPA 2 grams High EPA	Matched placebo corn oil capsules Placebo	Total of all reporting groups
Overall Participants	36	36	36	108
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.73 (16.14)	58.10 (10.16)	57.91 (11.68)	57.92 (12.79)
Sex: Female, Male (Count of Participants)
Female	15 41.7%	20 55.6%	23 63.9%	58 53.7%
Male	21 58.3%	16 44.4%	13 36.1%	50 46.3%
Race/Ethnicity, Customized (Count of Participants)
White	23 63.9%	15 41.7%	20 55.6%	58 53.7%
Black	13 36.1%	19 52.8%	16 44.4%	48 44.4%
Other	0 0%	2 5.6%	0 0%	2 1.9%
Region of Enrollment (participants) [Number]
United States	36 100%	36 100%	36 100%	108 100%
Treatment Site (Count of Participants)
Duke Unviersity Medical Center	12 33.3%	13 36.1%	13 36.1%	38 35.2%
Thomas Jefferson University	12 33.3%	10 27.8%	10 27.8%	32 29.6%
University of North Carolina	12 33.3%	13 36.1%	13 36.1%	38 35.2%
Hamilton Depression Rating Scale (HDRS) Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	22.2 (3.78)	22.67 (4.24)	23.56 (4.53)	22.82 (4.19)
Red Blood Cell/Plasma EPA (percentage of total fatty acids) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of total fatty acids]	0.48 (0.2)	0.51 (0.24)	0.49 (0.28)	0.49 (0.24)

Outcome Measures

1. Primary Outcome

Title	Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores.
Description	Endpoint HAMD scores are mean values adjusted for age, race, sex, treatment site, and the baseline HAMD value. The range for the HAMD scores is 0 to 52 with higher scores indicating a greater severity of depressive symptoms.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	2:1 EPA/DHA	High EPA	Placebo
Arm/Group Description	400/200 EPA/DHA fish oil 2 grams 2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams	Almost pure EPA 2 grams High EPA	Matched placebo corn oil capsules Placebo
Measure Participants	36	36	36
Mean (Standard Error) [units on a scale]	15.1 (0.9)	15.7 (0.9)	14.9 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2:1 EPA/DHA, Placebo
	Comments	The model used post-treatment HAMD values as the dependent variable and included age, race, sex, treatment site, and the baseline HAMD value as covariates. This analysis was conducted under intention-to-treat (ITT) in which the missing HAMD endpoint values were imputed using 50 imputations.
	Type of Statistical Test	Superiority
	Comments	The EPA/DHA arm versus placebo at Week 12.
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High EPA, Placebo
	Comments	The model used post-treatment HAMD values as the dependent variable and included age, race, sex, treatment site, and the baseline HAMD value as covariates. This analysis was conducted under intention-to-treat (ITT) in which the missing HAMD endpoint values were imputed using 50 imputations.
	Type of Statistical Test	Superiority
	Comments	High EPA group versus placebo group at Week 12.
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	ANCOVA
	Comments

2. Primary Outcome

Title	Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values.
Description	Endpoint EPA values are mean values adjusted for age, race, sex, treatment site, and the baseline EPA value. Red blood cell/plasma EPA values are expressed as a percent of total identified fatty acids.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The numbers at baseline reflect the total number of patients who provided samples for the assay of omega 3 percentage of total fatty acids. The numbers at endpoint reflect the total number of patients included in the intention to treat analysis.

Arm/Group Title	2:1 EPA/DHA	High EPA	Placebo
Arm/Group Description	400/200 EPA/DHA fish oil 2 grams 2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams	Almost pure EPA 2 grams High EPA	Matched placebo corn oil capsules Placebo
Measure Participants	36	36	36
Mean (Standard Error) [percentage of total fatty acids]	1.52 (0.15)	1.86 (0.15)	0.56 (0.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2:1 EPA/DHA, High EPA, Placebo
	Comments	The model used post-treatment EPA values as the dependent variable and included age, race, sex, treatment site, and the baseline EPA value as covariates. This analyses was conducted under intention-to-treat (ITT) in which the missing EPA endpoint values were imputed using 50 imputations.
	Type of Statistical Test	Superiority
	Comments	Active supplements (2:1 EPA/DHA and High EPA combined) versus placebo at Week 12.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2:1 EPA/DHA, High EPA
	Comments	The model used post-treatment EPA values as the dependent variable and included age, race, sex, treatment site, and the baseline EPA value as covariates. This analyses was conducted under intention-to-treat (ITT) in which the missing EPA endpoint values were imputed using 50 imputations.
	Type of Statistical Test	Superiority
	Comments	2:1 EPA/DHA versus High EPA at Week 12.
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	ANCOVA
	Comments

Adverse Events

Time Frame	Adverse events (AEs) were systematically monitored from enrollment, randomization, at the 12 week intervention and up until 30 days after study drug discontinuation. For patients who terminated from the study before the completion of the 12 week active intervention phase, a 30 day follow-up for AEs was ascertained.
Arm/Group Title	2:1 EPA/DHA		High EPA		Placebo
Arm/Group Description	400/200 EPA/DHA fish oil 2 grams 2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams		Almost pure EPA 2 grams High EPA		Matched placebo corn oil capsules Placebo
All Cause Mortality
	2:1 EPA/DHA		High EPA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)		0/36 (0%)		1/36 (2.8%)
Serious Adverse Events
	2:1 EPA/DHA		High EPA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/36 (11.1%)		5/36 (13.9%)		7/36 (19.4%)
Cardiac disorders
Heart Failure Exacerbation	2/36 (5.6%)	2	3/36 (8.3%)	4	6/36 (16.7%)	7
Cardiac Arrest	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Arrhythmia	1/36 (2.8%)	1	0/36 (0%)	0	1/36 (2.8%)	2
Chest Pain	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Chest Pain on Exertion	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Vascular disorders
Hypertensive Urgency	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Mild Stroke	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Other (Not Including Serious) Adverse Events
	2:1 EPA/DHA		High EPA		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/36 (19.4%)		6/36 (16.7%)		10/36 (27.8%)
Cardiac disorders
Chest Pain	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Hypotension	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Arrhythmia	1/36 (2.8%)	1	0/36 (0%)	0	1/36 (2.8%)	1
Syncope	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Heart failure exacerbation	0/36 (0%)	0	1/36 (2.8%)	1	1/36 (2.8%)	1
Eye disorders
Cataract Removal	2/36 (5.6%)	2	0/36 (0%)	0	0/36 (0%)	0
Gastrointestinal disorders
Non-Cardiac Chest Pain	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Dehydration	1/36 (2.8%)	1	0/36 (0%)	0	1/36 (2.8%)	1
Nausea	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Infections and infestations
Bacteremia	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Bacterial Infection	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Infection	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Influenza A	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Metabolism and nutrition disorders
Diabetes Mellitus	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Musculoskeletal and connective tissue disorders
Knee Pain	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Right Lower Back/Flank Pain	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Nerve Pain	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Arm Pain	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Lumbar Burst Fracture, With Acute Exacerbation	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Neck Pain	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Back pain	1/36 (2.8%)	1	0/36 (0%)	0	0/36 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute Pharyngitis	0/36 (0%)	0	0/36 (0%)	0	1/36 (2.8%)	1
Cough	0/36 (0%)	0	1/36 (2.8%)	1	0/36 (0%)	0
Skin and subcutaneous tissue disorders
Cellulitis	1/36 (2.8%)	1	0/36 (0%)	0	1/36 (2.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.