Hypertriglyceridemia
Conditions
Keywords
triglycerides, hypertriglyceridemia, omega-3, n-3, eicosapentaenoic acid, EPA, docosahexaenoic acid, DHA, flow mediated dilation, fish, Moderate hypertriglyceridemia
Brief summary
The purpose of this study is to evaluate the cardiovascular and lipid effects of two doses of an omega-3 fatty acid concentrate in a group of people who normally are not treated for high lipids.
Interventions
DRUG4/day of 4g P-OM3 capsules
4/day of 4g P-OM3 capsules for 8 weeks
DRUG4/day of 1g P-OM3 capsules
4/day of 1g P-OM3 capsules for 8 weeks
DRUGCorn Oil Placebo, 4 capsules/day for 8 weeks
4 capsules per day of corn oil placebo for 8 weeks
Sponsors
Reliant Pharmaceuticals
Penn State University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* triglycerides 150-500 mg/dL * age 21-65 years * generally healthy * body mass index (BMI) 20-39 kg/m2
Exclusion criteria
* smoking * premenopausal (if female) * use of hormone replacement or oral contraceptives * use of lipid lowering or blood pressure medication * hypertension (blood pressure \> 150/95 mm Hg) * peripheral vascular disease * heart disease, diabetes, or stroke * inflammatory disease (e.g. rheumatoid arthritis or Crohn's) * elevated liver enzymes * high intake of omega-3 containing foods * allergy to adhesive or latex * use of aspirin, anticoagulants, or SSRI
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Lipid Profile | 8 weeks | Plasma/serum samples were analyzed at baseline and at the end of each 8-week treatment period to evaluate the effect of P-OM3 dose on triglycerides, HDL-C, LDL-C, and total cholesterol. |
| Flow-mediated Dilation (FMD) | 8 weeks | Effect of P-OM3 dose on FMD, which is measured as percent change in brachial artery diameter at peak dilation vs. baseline following a 5-minute occlusion period. |
| Blood Pressure | 8 weeks | Effect of P-OM3 dose on blood pressure |
| Heart Rate | 8 weeks | Effect of P-OM3 dose on heart rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C-reactive Protein (CRP) | 8 weeks | Effect of P-OM3 dose on the plasma concentration of the inflammatory marker CRP |
| Erythrocyte Fatty Acids | 8 weeks | Effect of P-OM3 dose on the percent concentration of select omega-3 fatty acids in red blood cells |
| Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | 8 weeks | Effect of P-OM3 dose on the homeostatic model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). HOMA-IR calculates an index of insulin resistance and is calculated as follows: HOMA-IR = (glucose mg/dL \* insulin mU/L) / 405. QUICKI is calculated as follows: QUICKI = 1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL)). |
| Fasting Insulin | 8 weeks | Effect of P-OM3 dose on fasting insulin |
| Cytokine Inflammatory Markers | 8 weeks | Effect of P-OM3 dose on concentrations of circulating inflammatory markers in plasma |
| Fasting Glucose | 8 weeks | Effect of P-OM3 dose on fasting glucose |
| Psychosocial Profile Questionnaires | 8 weeks | Effect of P-OM3 dose on psychosocial questionnaires: Perceived Stress Scale (PSS) * 14 questions, scored 0-4 based on how often the subject felt certain emotions * Scores: 0 to 40; higher scores indicate higher perceived stress Spielberger State Anxiety Inventory * Levels of state anxiety (situational) and trait anxiety; 40 items scored by a Likert scale * Scores: 20 to 80; higher scores indicate higher levels of anxiety Positive and Negative Affect Scales (PANAS) * Two 10-item scales; each item is rated on a Likert scale of 1 (not at all) to 5 (very much). * Scores: 10 to 50, with higher scores representing higher levels of positive or negative affect Center for Epidemiologic Studies Depression (CES-D) Scale * 20 questions about symptoms of depression in the past week * Scores: 0 to 60; higher scores indicate more symptomology. Score of 16 or higher indicates a risk for depression and should be followed by further evaluation by a qualified health professional |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 4 g P-OM3, 1 g P-OM3, Placebo 4 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 1 g/d P-OM3 for 8 weeks, followed by 4 g/d corn oil placebo for 8 weeks | 7 |
| 1 g P-OM3, 4 g P-OM3, Placebo 1 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 4 g/d P-OM3 for 8 weeks, followed by 4 g/d corn oil placebo for 8 weeks | 5 |
| Placebo, 4 g P-OM3, 1 g P-OM3 4 g/d corn oil placebo for 8 weeks, followed by 4 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 1 g/d P-OM3 for 8 weeks | 1 |
| 4 g P-OM3, Placebo, 1 g P-OM3 4 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 4 g/d corn oil placebo for 8 weeks, followed by 1 g/d P-OM3 for 8 weeks | 3 |
| 1 g P-OM3, Placebo, 4 g P-OM3 1 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 4 g/d corn oil placebo for 8 weeks, followed by 4 g/d P-OM3 for 8 weeks | 7 |
| Placebo, 1 g P-OM3, 4 g P-OM3 4 g/d corn oil placebo for 8 weeks, followed by 1 g/d prescription omega-3 fatty acid ethyl esters (P-OM3) for 8 weeks, followed by 4 g/d P-OM3 for 8 weeks | 3 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | 4 g P-OM3, 1 g P-OM3, Placebo | 1 g P-OM3, 4 g P-OM3, Placebo | Placebo, 4 g P-OM3, 1 g P-OM3 | 4 g P-OM3, Placebo, 1 g P-OM3 | 1 g P-OM3, Placebo, 4 g P-OM3 | Placebo, 1 g P-OM3, 4 g P-OM3 | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 4 Participants | 1 Participants | 3 Participants | 7 Participants | 3 Participants | 25 Participants |
| Region of Enrollment United States | 7 participants | 5 participants | 1 participants | 3 participants | 7 participants | 3 participants | 26 participants |
| Sex: Female, Male Female | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1 / 27 | 0 / 27 | 0 / 28 |
| serious Total, serious adverse events | 0 / 27 | 0 / 27 | 0 / 28 |
Outcome results
Primary
Blood Pressure
Effect of P-OM3 dose on blood pressure
Time frame: 8 weeks
Population: Two participants did not complete the study and were therefore excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Blood Pressure | Diastolic blood pressure (DBP) | 76.1 mm Hg | Standard Error 1.6 |
| 4g P-OM3 | Blood Pressure | Systolic blood pressure (SBP) | 126.3 mm Hg | Standard Error 2.2 |
| 1g P-OM3 | Blood Pressure | Diastolic blood pressure (DBP) | 77.7 mm Hg | Standard Error 1.6 |
| 1g P-OM3 | Blood Pressure | Systolic blood pressure (SBP) | 129.0 mm Hg | Standard Error 2.2 |
| Placebo | Blood Pressure | Diastolic blood pressure (DBP) | 77.8 mm Hg | Standard Error 1.6 |
| Placebo | Blood Pressure | Systolic blood pressure (SBP) | 128.4 mm Hg | Standard Error 2.2 |
Primary
Flow-mediated Dilation (FMD)
Effect of P-OM3 dose on FMD, which is measured as percent change in brachial artery diameter at peak dilation vs. baseline following a 5-minute occlusion period.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4g P-OM3 | Flow-mediated Dilation (FMD) | 5.00 % change in brachial artery diameter | Standard Error 0.5 |
| 1g P-OM3 | Flow-mediated Dilation (FMD) | 4.03 % change in brachial artery diameter | Standard Error 0.5 |
| Placebo | Flow-mediated Dilation (FMD) | 5.00 % change in brachial artery diameter | Standard Error 0.5 |
Primary
Heart Rate
Effect of P-OM3 dose on heart rate
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4g P-OM3 | Heart Rate | 67.9 beats per minute | Standard Error 1.8 |
| 1g P-OM3 | Heart Rate | 69.8 beats per minute | Standard Error 1.8 |
| Placebo | Heart Rate | 71.8 beats per minute | Standard Error 1.8 |
Primary
Lipid Profile
Plasma/serum samples were analyzed at baseline and at the end of each 8-week treatment period to evaluate the effect of P-OM3 dose on triglycerides, HDL-C, LDL-C, and total cholesterol.
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Lipid Profile | High density lipoprotein-cholesterol (HDL-C) | 43.2 mg/dL | Standard Error 1.9 |
| 4g P-OM3 | Lipid Profile | Low density lipoprotein-cholesterol (LDL-C) | 130.3 mg/dL | Standard Error 7.6 |
| 4g P-OM3 | Lipid Profile | Total Cholesterol | 207.9 mg/dL | Standard Error 7.9 |
| 4g P-OM3 | Lipid Profile | Triglycerides | 173.7 mg/dL | Standard Error 17.5 |
| 1g P-OM3 | Lipid Profile | Triglycerides | 215.3 mg/dL | Standard Error 17.5 |
| 1g P-OM3 | Lipid Profile | High density lipoprotein-cholesterol (HDL-C) | 42.7 mg/dL | Standard Error 1.9 |
| 1g P-OM3 | Lipid Profile | Total Cholesterol | 212.1 mg/dL | Standard Error 7.9 |
| 1g P-OM3 | Lipid Profile | Low density lipoprotein-cholesterol (LDL-C) | 127.6 mg/dL | Standard Error 7.6 |
| Placebo | Lipid Profile | Triglycerides | 237.3 mg/dL | Standard Error 17.5 |
| Placebo | Lipid Profile | Low density lipoprotein-cholesterol (LDL-C) | 123.3 mg/dL | Standard Error 7.6 |
| Placebo | Lipid Profile | Total Cholesterol | 209 mg/dL | Standard Error 7.9 |
| Placebo | Lipid Profile | High density lipoprotein-cholesterol (HDL-C) | 42.6 mg/dL | Standard Error 1.9 |
Comparison: Fasting triglycerides (mg/dL) were measured on two consecutive days and averaged for analysis at the end of each treatment period. The null hypothesis was that triglycerides did not differ between groups.p-value: 0.002Mixed Models Analysis
Comparison: Cholesterol values were compared as the average of two fasting values at the end of each treatment. Cholesterol values included LDL-C, HDL-C, total cholesterol, and calculated ratios.p-value: >0.05Mixed Models Analysis
Secondary
C-reactive Protein (CRP)
Effect of P-OM3 dose on the plasma concentration of the inflammatory marker CRP
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4g P-OM3 | C-reactive Protein (CRP) | 1.29 mg/L | Standard Error 0.2 |
| 1g P-OM3 | C-reactive Protein (CRP) | 1.32 mg/L | Standard Error 0.2 |
| Placebo | C-reactive Protein (CRP) | 1.45 mg/L | Standard Error 0.2 |
Secondary
Cytokine Inflammatory Markers
Effect of P-OM3 dose on concentrations of circulating inflammatory markers in plasma
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Cytokine Inflammatory Markers | Interleuken-6 (IL-6) | 0.87 pg/mL | Standard Error 0.15 |
| 4g P-OM3 | Cytokine Inflammatory Markers | Interleuken-1β (IL-1β) | 0.14 pg/mL | Standard Error 0.02 |
| 4g P-OM3 | Cytokine Inflammatory Markers | Tumor Necrosis Factor-α (TNF-α) | 1.00 pg/mL | Standard Error 0.07 |
| 1g P-OM3 | Cytokine Inflammatory Markers | Interleuken-6 (IL-6) | 0.85 pg/mL | Standard Error 0.15 |
| 1g P-OM3 | Cytokine Inflammatory Markers | Interleuken-1β (IL-1β) | 0.15 pg/mL | Standard Error 0.02 |
| 1g P-OM3 | Cytokine Inflammatory Markers | Tumor Necrosis Factor-α (TNF-α) | 1.11 pg/mL | Standard Error 0.14 |
| Placebo | Cytokine Inflammatory Markers | Interleuken-1β (IL-1β) | 0.15 pg/mL | Standard Error 0.02 |
| Placebo | Cytokine Inflammatory Markers | Tumor Necrosis Factor-α (TNF-α) | 1.20 pg/mL | Standard Error 0.14 |
| Placebo | Cytokine Inflammatory Markers | Interleuken-6 (IL-6) | 0.87 pg/mL | Standard Error 0.15 |
Secondary
Erythrocyte Fatty Acids
Effect of P-OM3 dose on the percent concentration of select omega-3 fatty acids in red blood cells
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Erythrocyte Fatty Acids | Docosahexaenoic acid (DHA) | 6.49 percentage | Standard Error 0.15 |
| 4g P-OM3 | Erythrocyte Fatty Acids | Eicosapentaenoic acid (EPA) | 2.30 percentage | Standard Error 0.09 |
| 4g P-OM3 | Erythrocyte Fatty Acids | Omega-3 Index (EPA + DHA) | 8.79 percentage | Standard Error 0.21 |
| 1g P-OM3 | Erythrocyte Fatty Acids | Docosahexaenoic acid (DHA) | 5.34 percentage | Standard Error 0.15 |
| 1g P-OM3 | Erythrocyte Fatty Acids | Eicosapentaenoic acid (EPA) | 1.15 percentage | Standard Error 0.09 |
| 1g P-OM3 | Erythrocyte Fatty Acids | Omega-3 Index (EPA + DHA) | 6.49 percentage | Standard Error 0.21 |
| Placebo | Erythrocyte Fatty Acids | Eicosapentaenoic acid (EPA) | 0.57 percentage | Standard Error 0.09 |
| Placebo | Erythrocyte Fatty Acids | Omega-3 Index (EPA + DHA) | 4.96 percentage | Standard Error 0.21 |
| Placebo | Erythrocyte Fatty Acids | Docosahexaenoic acid (DHA) | 4.39 percentage | Standard Error 0.15 |
Secondary
Fasting Glucose
Effect of P-OM3 dose on fasting glucose
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4g P-OM3 | Fasting Glucose | 99.2 mg/dL | Standard Error 1.9 |
| 1g P-OM3 | Fasting Glucose | 98.0 mg/dL | Standard Error 1.9 |
| Placebo | Fasting Glucose | 96.1 mg/dL | Standard Error 2 |
Secondary
Fasting Insulin
Effect of P-OM3 dose on fasting insulin
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4g P-OM3 | Fasting Insulin | 15.0 μIU/mL | Standard Error 1.4 |
| 1g P-OM3 | Fasting Insulin | 15.5 μIU/mL | Standard Error 1.4 |
| Placebo | Fasting Insulin | 14.6 μIU/mL | Standard Error 1.4 |
Secondary
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI)
Effect of P-OM3 dose on the homeostatic model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI). HOMA-IR calculates an index of insulin resistance and is calculated as follows: HOMA-IR = (glucose mg/dL \* insulin mU/L) / 405. QUICKI is calculated as follows: QUICKI = 1 / (log(fasting insulin µU/mL) + log(fasting glucose mg/dL)).
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | HOMA-IR | 3.64 index units | Standard Error 0.4 |
| 4g P-OM3 | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | QUICKI | 0.14 index units | Standard Error 0.002 |
| 1g P-OM3 | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | HOMA-IR | 3.75 index units | Standard Error 0.4 |
| 1g P-OM3 | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | QUICKI | 0.14 index units | Standard Error 0.002 |
| Placebo | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | HOMA-IR | 3.55 index units | Standard Error 0.4 |
| Placebo | Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI) | QUICKI | 0.14 index units | Standard Error 0.002 |
Secondary
Psychosocial Profile Questionnaires
Effect of P-OM3 dose on psychosocial questionnaires: Perceived Stress Scale (PSS) * 14 questions, scored 0-4 based on how often the subject felt certain emotions * Scores: 0 to 40; higher scores indicate higher perceived stress Spielberger State Anxiety Inventory * Levels of state anxiety (situational) and trait anxiety; 40 items scored by a Likert scale * Scores: 20 to 80; higher scores indicate higher levels of anxiety Positive and Negative Affect Scales (PANAS) * Two 10-item scales; each item is rated on a Likert scale of 1 (not at all) to 5 (very much). * Scores: 10 to 50, with higher scores representing higher levels of positive or negative affect Center for Epidemiologic Studies Depression (CES-D) Scale * 20 questions about symptoms of depression in the past week * Scores: 0 to 60; higher scores indicate more symptomology. Score of 16 or higher indicates a risk for depression and should be followed by further evaluation by a qualified health professional
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 4g P-OM3 | Psychosocial Profile Questionnaires | CES-D | 3.4 scores on a scale | Standard Error 2.9 |
| 4g P-OM3 | Psychosocial Profile Questionnaires | Negative Scale (PANAS) | 11.7 scores on a scale | Standard Error 2.4 |
| 4g P-OM3 | Psychosocial Profile Questionnaires | Positive Scale (PANAS) | 34.1 scores on a scale | Standard Error 2.2 |
| 4g P-OM3 | Psychosocial Profile Questionnaires | Perceived Stress Scale (PSS) | 23.2 scores on a scale | Standard Error 2.2 |
| 4g P-OM3 | Psychosocial Profile Questionnaires | Spielberger State Anxiety Inventory | 46.2 scores on a scale | Standard Error 1.5 |
| 1g P-OM3 | Psychosocial Profile Questionnaires | Negative Scale (PANAS) | 13.3 scores on a scale | Standard Error 2.5 |
| 1g P-OM3 | Psychosocial Profile Questionnaires | Positive Scale (PANAS) | 35.0 scores on a scale | Standard Error 2.4 |
| 1g P-OM3 | Psychosocial Profile Questionnaires | Perceived Stress Scale (PSS) | 23.7 scores on a scale | Standard Error 2.4 |
| 1g P-OM3 | Psychosocial Profile Questionnaires | CES-D | 3.3 scores on a scale | Standard Error 3.1 |
| 1g P-OM3 | Psychosocial Profile Questionnaires | Spielberger State Anxiety Inventory | 46.5 scores on a scale | Standard Error 1.6 |
| Placebo | Psychosocial Profile Questionnaires | Spielberger State Anxiety Inventory | 45.0 scores on a scale | Standard Error 1.6 |
| Placebo | Psychosocial Profile Questionnaires | CES-D | 2.2 scores on a scale | Standard Error 3 |
| Placebo | Psychosocial Profile Questionnaires | Perceived Stress Scale (PSS) | 22.3 scores on a scale | Standard Error 2.3 |
| Placebo | Psychosocial Profile Questionnaires | Negative Scale (PANAS) | 11.9 scores on a scale | Standard Error 2.4 |
| Placebo | Psychosocial Profile Questionnaires | Positive Scale (PANAS) | 35.2 scores on a scale | Standard Error 2.3 |