Omega-3 Fatty Acids and Insulin Sensitivity

Insulin Resistance Clinical Trial

Official title:

Dietary Omega-3 Fatty Acids as a Therapeutic Strategy in Insulin Resistant Humans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01686568
• Other study ID #: 12-004590
• Secondary ID: KL2TR000136U24DK
• Status: Completed
• Phase: Phase 3
• First received: September 11, 2012
• Last updated: June 16, 2015
• Start date: December 2012
• Est. completion date: June 2015

Study information

• Verified date: June 2015
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study is being done to understand the effects of dietary omega-3 fats on insulin sensitivity in adult men and women.

Description:

Dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), which include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil, prevent insulin resistance in rodents, but data in humans is ambiguous. No existing studies have systematically evaluated the influence of n-3 PUFAs on insulin sensitivity and beta cell function in insulin resistant, non-diabetic humans. The Investigators hypothesize that 6 months of oral supplementation of purified EPA/DHA (3.9g/day) will significantly improve hepatic and peripheral insulin sensitivity and beta cell responsiveness in insulin-resistant, non-diabetic individuals. Based on recent work in mice, the investigators also hypothesize that EPA/DHA will increase the content and function of mitochondria in skeletal muscle, measured using a combination of in vivo and in vitro methods. Overall, the investigators hypothesize that EPA+DHA supplementation will improve hepatic and peripheral insulin sensitivity in insulin resistant humans, and this improvement will be associated with mitochondrial biogenesis and attenuated lipid accumulation in skeletal muscle and liver.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: June 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

1. Age 18-65 years

2. Insulin resistant (Homeostasis Model Assessment (HOMA) Insulin Resistance (IR) =2.6)

Exclusion criteria:

1. Current use of omega-3 nutritional supplements

2. Fasting plasma glucose =126 mg/dL

3. Active coronary artery disease

4. Participation in structured exercise (>2 times per week for 30 minutes or longer)

5. Smoking

6. Medications known to affect muscle metabolism (e.g., beta blockers, corticosteroids, tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, anticoagulants)

7. Renal failure (serum creatinine > 1.5mg/dl)

8. Chronic active liver disease (AST>144 IU/L and alanine transaminase (ALT)>165 IU/L)

9. Anti-coagulant therapy (warfarin/heparin)

10. International normalized ratio (INR) >3

11. Use of systemic glucocorticoids

12. Chronic use of NSAIDS or aspirin

13. Pregnancy or breastfeeding

14. Alcohol consumption greater than 2 glasses/day

15. Hypothyroidism

16. Fish or shellfish allergy

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Insulin Resistance

Intervention

Drug:
• Omega-3
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
• placebo

Locations

Country	Name	City	State
United States	Mayo Clinic in Rochester	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Mayo Clinic	National Center for Advancing Translational Science (NCATS), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (1)

Lalia AZ, Johnson ML, Jensen MD, Hames KC, Port JD, Lanza IR. Effects of Dietary n-3 Fatty Acids on Hepatic and Peripheral Insulin Sensitivity in Insulin-Resistant Humans. Diabetes Care. 2015 Jul;38(7):1228-37. doi: 10.2337/dc14-3101. Epub 2015 Apr 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up	A 2-stage insulin clamp will be performed with titration of dextrose to maintain euglycemia. D2 glucose will be infused to evaluate hepatic glucose production at baseline and in response to insulin. Hyperinsulinemic-euglycemic clamp technique: The plasma insulin concentration is acutely raised and maintained by a continuous infusion of insulin. Meanwhile, the plasma glucose concentration is held constant at basal levels by a variable glucose infusion. When the steady-state is achieved, the glucose infusion rate (GIR) equals glucose uptake by all the tissues in the body and is therefore a measure of tissue insulin sensitivity.	Baseline, after 6 months of treatment	No
Secondary	Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up	Following consumption of a mixed meal, beta cell function will be evaluated from serial measurements of C-peptide. C-peptide was measured using a two-side immunometric assay using electrochemiluminescence detection.	baseline, after 6 months of treatment	No
Secondary	Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up	Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.	Baseline, after 6 months of treatment	No