Depression
Conditions
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.
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.
Interventions
DRUG2:1 EPA/DHA
400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams
DRUGHigh EPA
OTHERPlacebo
Sponsors
National Institute of Mental Health (NIMH)
Wei Jiang
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 2:1 EPA/DHA 400/200 EPA/DHA fish oil 2 grams
2:1 EPA/DHA: 400 Eicosapentaenoic acid/200 docosahexaenoic acid fish oil 2 grams | 36 |
| High EPA Almost pure EPA 2 grams
High EPA | 36 |
| Placebo Matched placebo corn oil capsules
Placebo | 36 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 |
| Overall Study | Patient transportation issues | 0 | 0 | 1 |
| Overall Study | Physician Decision | 0 | 0 | 2 |
| Overall Study | Protocol Violation | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 | 0 |
Baseline characteristics
| Characteristic | 2:1 EPA/DHA | Total | Placebo | High EPA |
|---|---|---|---|---|
| Age, Continuous | 57.73 years STANDARD_DEVIATION 16.14 | 57.92 years STANDARD_DEVIATION 12.79 | 57.91 years STANDARD_DEVIATION 11.68 | 58.10 years STANDARD_DEVIATION 10.16 |
| Hamilton Depression Rating Scale (HDRS) Score | 22.2 units on a scale STANDARD_DEVIATION 3.78 | 22.82 units on a scale STANDARD_DEVIATION 4.19 | 23.56 units on a scale STANDARD_DEVIATION 4.53 | 22.67 units on a scale STANDARD_DEVIATION 4.24 |
| Race/Ethnicity, Customized Black | 13 Participants | 48 Participants | 16 Participants | 19 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized White | 23 Participants | 58 Participants | 20 Participants | 15 Participants |
| Red Blood Cell/Plasma EPA | 0.48 percentage of total fatty acids STANDARD_DEVIATION 0.2 | 0.49 percentage of total fatty acids STANDARD_DEVIATION 0.24 | 0.49 percentage of total fatty acids STANDARD_DEVIATION 0.28 | 0.51 percentage of total fatty acids STANDARD_DEVIATION 0.24 |
| Region of Enrollment United States | 36 participants | 108 participants | 36 participants | 36 participants |
| Sex: Female, Male Female | 15 Participants | 58 Participants | 23 Participants | 20 Participants |
| Sex: Female, Male Male | 21 Participants | 50 Participants | 13 Participants | 16 Participants |
| Treatment Site Duke Unviersity Medical Center | 12 Participants | 38 Participants | 13 Participants | 13 Participants |
| Treatment Site Thomas Jefferson University | 12 Participants | 32 Participants | 10 Participants | 10 Participants |
| Treatment Site University of North Carolina | 12 Participants | 38 Participants | 13 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 36 | 0 / 36 | 1 / 36 |
| other Total, other adverse events | 7 / 36 | 6 / 36 | 10 / 36 |
| serious Total, serious adverse events | 4 / 36 | 5 / 36 | 7 / 36 |
Outcome results
Primary
Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores.
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2:1 EPA/DHA | Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores. | 15.1 units on a scale | Standard Error 0.9 |
| High EPA | Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores. | 15.7 units on a scale | Standard Error 0.9 |
| Placebo | Endpoint Hamilton Depression Rating Scale (HAMD) Scores Adjusted for Age, Sex, Treatment Site, and Baseline HAMD Scores. | 14.9 units on a scale | Standard Error 0.9 |
Comparison: 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.p-value: 0.74ANCOVA
Comparison: 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.p-value: 0.45ANCOVA
Primary
Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values.
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
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 2:1 EPA/DHA | Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values. | 1.52 percentage of total fatty acids | Standard Error 0.15 |
| High EPA | Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values. | 1.86 percentage of total fatty acids | Standard Error 0.15 |
| Placebo | Endpoint Red Blood Cell/Plasma EPA Values Adjusted for Age, Sex, Treatment Site, and Baseline Red Blood Cell/Plasma EPA Values. | 0.56 percentage of total fatty acids | Standard Error 0.15 |
Comparison: 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.p-value: <0.0001ANCOVA
Comparison: 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.p-value: 0.12ANCOVA