Clinical trial NCT03120299: The Effect of Omega-3 FA on Hypertriglyceridemia in Patients With T2DM(OCEAN)
Official title: The Effect of Omega-3 Fatty Acids on Hypertriglyceridemia in Patients With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Hypertriglyceridemia
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2017-04-19
Enrollment: 309
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Primary outcomes:
measure: Change in serum triglycerides from baseline
timeFrame: 12 weeks
measure: Change in blood metabolomics profile of lipid species from baseline
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in serum metabolomics profile of bile acids from baseline
timeFrame: 12 weeks
measure: Change in serum metabolomics profile of amino acid species from baseline
timeFrame: 12 weeks
measure: Change in Gut microbiome from baseline
timeFrame: 12 weeks
measure: Change in fasting glucose levels from baseline
timeFrame: 12 weeks
measure: Change in 2-hour postprandial glucose levels from baseline
timeFrame: 12 weeks
measure: Change in HbA1c from baseline
timeFrame: 12 weeks
measure: Change in Non-HDL-C from baseline
timeFrame: 12 weeks
measure: Change in serum total Cholesterol from baseline
timeFrame: 12 weeks
measure: Change in serum VLDL-c from baseline
timeFrame: 12 weeks
measure: Change in serum HDL-c from baseline
timeFrame: 12 weeks
measure: Change in serum LDL-c from baseline
timeFrame: 12 weeks
measure: Change in LDL-C/HDL-C from baseline
timeFrame: 12 weeks
measure: Change in serum Apo B from baseline
timeFrame: 12 weeks
measure: Change in serum AST from baseline
timeFrame: 12 weeks
measure: Change in serum ALT from baseline
timeFrame: 12 weeks
measure: Change in serum inflammation markers from baseline
timeFrame: 12 weeks
measure: Change in liver fat content from baseline
timeFrame: 12 weeks
measure: Change in Ankle-Brachial Index from baseline
timeFrame: 12 weeks
measure: Change in Brachial-ankle pulse wave velocity from baseline
timeFrame: 12 weeks
measure: Change in enrichment of fish oil in red blood cell from baseline
timeFrame: 12 weeks
measure: Pharmacogenomics analysis
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin hospital, Shanghai Jiao-Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Ruijin Hospital
name: Guang Ning, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: