The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)

The purpose of this study is to conduct a multicenter randomized, double-blind, placebo-controlled clinical trial, evaluating the effects and change of lipid metabolism, especially of triglyceride after omega-3 administration in type 2 diabetes patients with hypertriglyceride.

In the present study, patients with type 2 diabetes and hypertriglyceride will be enrolled from multiple centers in China. Randomization was computer generated and stratified by center. After screening, eligible subjects will be randomly assigned into one of the following two groups: Omega-3 fatty acids capsules ( 2pills bid) and placebo capsules (2pills bid).

Blood, feces and urine samples will be collected before and after treatment. Triglycerides (TG), total cholesterol (TC), LDL-C, HDL-C, HbA1C, fasting plasma glucose (FPG), postprandial plasma glucose (PPG) will be measured. Blood metabolomics profiles of lipids, amino acids, bile acids, the change of gut microbiota, and pharmacogenomic components and parameters will be evaluated too.

Sample Size Calculation:

The primary clinical endpoint involves comparing changes in triglyceride (TG) levels between the placebo group and the omega-3 treatment group after a 12-week intervention. According to literature reports \[Borthwick L J. The effects of an omega-3 ethyl ester concentrate on blood lipid concentrations in patients with hyperlipidaemia\[J\]. Clinical drug investigation, 1998, 15(5): 397-404\], following 12 weeks of n-3 or placebo-controlled treatment, patients with hypertriglyceridemia exhibited a 9.1±24.8% increase in the placebo group and a 28.3±19.1% decrease in the omega-3 treatment group (4g/day). Based on this data, we conservatively estimate no change in TG in the placebo group for this trial, while anticipating a 10% reduction in the omega-3 treatment group. With a combined standard deviation (SD) of 30%, α=0.05, β=0.2, we calculate the sample size based on the mean difference between the two groups, resulting in N1=N2=143 cases.

Taking into account actual follow-up rates from preliminary research, we adjusted the estimated dropout rate from 20% to 5% and recalculated the sample size. Consequently, we plan to enroll 300 cases, with 150 in each of the omega-3 treatment and placebo groups, respectively.

Eligibility Criteria:
Inclusion Criteria:

1. Diagnosed type 2 diabetes defined as WHO (1999) diagnostic criteria ; Both Genders Eligible;
2. Men or women aged 20 to 75 years;
3. Stable dosage of oral anti-diabetic medicine ,stable glycemia control(HbA1c\<7.5%), unchanged antidiabetic therapy during the trial;
4. Hypertriglycerides (3.4mmol/L≤mean fasting blood triglycerides\<22.60mmol/L, and not receiving any lipid lowering therapy for 3 days continuously or accumulated 7 days within 6 weeks before screening).

Exclusion Criteria:

1. Uncontrolled blood pressure (defined as systolic blood pressure\>180mmHg or diastolic blood pressure\>100mmHg);
2. Other diseases affecting lipid and glucose metabolism: hyperthyroidism，cushing syndrome ect;
3. Receiving insulin treatment in 6 months before recruitment;
4. Diagnosed heart failure, defined as New York Heart Association class III or IV;
5. Histories of acute or chronic pancreatitis，or cholelithiasis （except those received cholecystectomy）
6. Significant impaired liver function (defined as alanine transaminase (ALT)\> 3 times upper limit of normal), or active liver disease;
7. PLT\<60×10\^9/L，Hb\<100g/L；
8. Impaired renal function (defined as serum creatinine\> 135 mmol/L（1.5 mg/dL, male) and \> 110 mmol/L （1.3 mg/dL,female）；
9. Recorded history of malignant tumor in the past 2 years;
10. Histories of acute cerebrovascular accident within 6 months;
11. Pregnancy;
12. Known history of allergy to fish, shellfish and omega-3 fatty acids, or ineffective treatment of omega-3 fatty acids;
13. Simultaneous participation in any other clinical trial of an active pharmacologic agent within 30 days;
14. Other situations that interfere with the subject's ability to comply with study instructions;
15. Any other condition that investigators believe would interfere with the subject's ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the subject at undue risk.