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

Phase 4CompletedNCT03120299

Shanghai Jiao Tong University School of Medicine309 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

309

Conditions

Type 2 Diabetes Mellitus Hypertriglyceridemia

Interventions

Omega-3 fatty acidDRUG

Omega-3 fatty acids capsules, 1 gram gel capsule, 2 capsules orally administered twice a day for 12 weeks

PlacebosDRUG

Matching placebo capsules, 1 gram gel capsule, 2 capsules orally administered twice a day for 12 weeks

Eligibility

Sex: ALLMin age: 20 YearsMax age: 75 Years

Medical Language ↔ Plain English

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.

Locations (1)

Ruijin hospital, Shanghai Jiao-Tong University School of Medicine

Shanghai, Shanghai Municipality, China

Outcomes

Primary Outcomes

Change in serum triglycerides from baseline

With aid of autoanalyser, the investigators will measure the serum triglycerides in blood samples before and after treatment.

Time frame: 12 weeks

Change in blood metabolomics profile of lipid species from baseline

With aid of LC/MS and GC/MS, the investigators will measure blood metabolomics profile of lipid species before and after treatment. The metabolomics measurement will help to detect the profile of all kinds of lipids species. The composition change of all these biological molecular induced by the treatment is our major interest rather than single molecular quantification.

Time frame: 12 weeks

Secondary Outcomes

Change in serum metabolomics profile of bile acids from baseline

With aid of LC/MS and GC/MS technique, the investigators will measure the blood metabolomics molecular profile of bile acids in blood samples before and after treatment.

Time frame: 12 weeks

Change in serum metabolomics profile of amino acid species from baseline

With aid of LC/MS and GC/MS technique, the investigators will measure the blood metabolomics molecular profile of amino acid species before and after treatment.

Time frame: 12 weeks

Change in Gut microbiome from baseline

With aid of quantitative real-time PCR technique, the investigators will measure gut microbiome in fecal samples before and after treatment.

Time frame: 12 weeks

Change in fasting glucose levels from baseline

With aid of autoanalyser, the investigators will measure fasting glucose levels before and after treatment.

Data from ClinicalTrials.gov

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