Hypertriglyceridemia
Conditions
Brief summary
The objectives of this study are to assess the effects of 4 g/d prescription omega-3 acid ethyl esters (POM3), compared with a placebo, on indices of insulin sensitivity and secretion, as well as aspects of the fasting and postprandial lipid and lipoprotein profiles, in subjects with hypertriglyceridemia.
Detailed description
This trial will utilize a randomized, double-blind, two-period crossover design. At Visit 2 (Week 0), subjects meeting all entry criteria will be randomized to one of two treatment sequences: placebo or POM3 for the first 6 week phase followed by the study product they did not receive during the first phase (POM3 or placebo) for the second 6 weeks. There will be a 2-week washout period between treatment phases.
Interventions
DRUGPOM3
4 g/day
DRUGPlacebo
matching placebo capsule, 4 g/day
Sponsors
GlaxoSmithKline
Provident Clinical Research
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Men and postmenopausal women, ages 18-79 years. * Fasting, triglyceride (TG) level in the borderline high to high range. * Fasting, low density lipoprotein cholesterol (LDL-C) below the very high range while on no lipid altering therapy or while taking stable-dose statin therapy * Provide written informed consent and authorization for protected health information
Exclusion criteria
* Use of any lipid-altering medications, which cannot be stopped, except stable dose statin therapy. * Use of any omega-3 fatty acid ethyl ester medications or dietary supplements with \>1.0 g/d of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a combination of EPA and DHA * coronary heart disease (CHD) or a CHD risk equivalent * Body mass index over 45 kg per square meter * Allergy or sensitivity to omega-3 fatty acids, corn or corn products (e.g., corn oil), D-alpha tocopherol (vitamin E) or any ingredients in the study drug * Certain muscle, liver, kidney, lung or gastrointestinal conditions * Poorly controlled hypertension * Certain medications * Active cancers treated within prior 2 years (except non-melanoma skin cancer)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Treatments in Liquid Meal Tolerance Test (LMTT) Matsuda Insulin Sensitivity Index (MISI). | End of Treatment Intervention Period I (week 6) and End of Treatment Intervention Period II (week 14) | Liquid meal tolerance test (LMTT) = two 8 oz servings of Ensure (Abbott Nutrition) + study product followed by blood sample collection at -5, -1, 30, 60, 90, 120, 180, and 240 min, where t = 0 was start of liquid meal consumption. MISI calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | End of Treatment Intervention Period I (week 6) and End of Treatment Intervention Period II (week 14) | Insulin secretion index = total area under the curve from 0 to 120 min post-meal for plasma insulin divided by total area under the curve from 0 to 120 min post-meal for plasma glucose. Disposition index = MISI x insulin secretion index |
Countries
United States
Participant flow
Recruitment details
Recruitment was conducted using the research clinic database and print advertisements. First subject screened in May 2010 and screening ended in August 2010.
Participants by arm
| Arm | Count |
|---|---|
| Prescription Omega-3 Acid Ethyl Esters (POM3)/Placebo POM3 for the first six weeks of treatment. Placebo for the second six weeks of treatment | 11 |
| Placebo/Prescription Omega-3 Acid Ethyl Esters (POM3) Placebo for the first six weeks of treatment. POM3 for the second six weeks of treatment | 12 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo/Prescription Omega-3 Acid Ethyl Esters (POM3) | Prescription Omega-3 Acid Ethyl Esters (POM3)/Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 8 Participants | 17 Participants |
| Age, Continuous | 60.0 years STANDARD_DEVIATION 1.7 | 47.9 years STANDARD_DEVIATION 5 | 54.2 years STANDARD_DEVIATION 2.8 |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 8 Participants | 3 Participants | 11 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 23 | 7 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Difference Between Treatments in Liquid Meal Tolerance Test (LMTT) Matsuda Insulin Sensitivity Index (MISI).
Liquid meal tolerance test (LMTT) = two 8 oz servings of Ensure (Abbott Nutrition) + study product followed by blood sample collection at -5, -1, 30, 60, 90, 120, 180, and 240 min, where t = 0 was start of liquid meal consumption. MISI calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin)
Time frame: End of Treatment Intervention Period I (week 6) and End of Treatment Intervention Period II (week 14)
Population: Per protocol population in which subjects with poor compliance, protocol violations, and without at least one post-randomization outcome data point during each treatment intervention period were removed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control | Difference Between Treatments in Liquid Meal Tolerance Test (LMTT) Matsuda Insulin Sensitivity Index (MISI). | 3.2 Index value |
| Prescription Omega-3 Acid Ethyl Esters | Difference Between Treatments in Liquid Meal Tolerance Test (LMTT) Matsuda Insulin Sensitivity Index (MISI). | 3.3 Index value |
Comparison: An evaluable sample of 19 subjects provided 80% power (5% alpha-level, 2-tailed) to detect a 2.1 unit difference between control and active in MISI, assuming a 3.0 unit standard deviation (SD). Repeated measures ANOVA was used to assess responses to treatment. Initial repeated measures models contained terms of treatment period, and sequence as fixed effects, with subject modeled as random effect; models were reduced until only significant terms or treatment remained.p-value: 0.959ANOVA
Secondary
Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index.
Insulin secretion index = total area under the curve from 0 to 120 min post-meal for plasma insulin divided by total area under the curve from 0 to 120 min post-meal for plasma glucose. Disposition index = MISI x insulin secretion index
Time frame: End of Treatment Intervention Period I (week 6) and End of Treatment Intervention Period II (week 14)
Population: Per protocol population excluding subjects with poor compliance and protocol violations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Control | Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | Disposition index | 2.4 Index value | Standard Error 0.25 |
| Control | Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | Insulin secretion index | 0.73 Index value | Standard Error 0.09 |
| Prescription Omega-3 Acid Ethyl Esters | Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | Insulin secretion index | 0.66 Index value | Standard Error 0.09 |
| Prescription Omega-3 Acid Ethyl Esters | Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | Disposition index | 2.1 Index value | Standard Error 0.2 |
p-value: 0.037ANOVA
p-value: 0.073ANOVA