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Insulin ResistancePhase 3NCT01686568

Omega-3 Fatty Acids and Insulin Sensitivity

A Phase 3 study testing Omega-3 in people with Insulin Resistance, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Insulin Resistance
What is being tested?
Omega-3
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
31 participants
Where
1 siteUnited States
Study dates
21 Dec 2012to 8 Jun 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • Age 18-65 years
  • Insulin resistant (Homeostasis Model Assessment (HOMA) Insulin Resistance (IR) ≥2.6)

Who cannot join

  • Current use of omega-3 nutritional supplements
  • Fasting plasma glucose ≥126 mg/dL
  • Active coronary artery disease
  • Participation in structured exercise (>2 times per week for 30 minutes or longer)
  • Smoking
  • Medications known to affect muscle metabolism (e.g., beta blockers, corticosteroids, tricyclic-antidepressants, benzodiazepines, opiates, barbiturates, anticoagulants)
Show all 16Show fewer
  • Renal failure (serum creatinine > 1.5mg/dl)
  • Chronic active liver disease (AST>144 IU/L and alanine transaminase (ALT)>165 IU/L)
  • Anti-coagulant therapy (warfarin/heparin)
  • International normalized ratio (INR) >3
  • Use of systemic glucocorticoids
  • Chronic use of NSAIDS or aspirin
  • Pregnancy or breastfeeding
  • Alcohol consumption greater than 2 glasses/day
  • Hypothyroidism
  • Fish or shellfish allergy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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

Read the detailed 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.

A sub-study was added in which participants receiving dietary omega-3 fatty acids or placebo supplements underwent abdominal subcutaneous adipose tissue biopsies to measure the content of total, pro- (M1) and anti- (M2) inflammatory macrophages (immunohistochemistry), crown-like structures (immunohistochemistry), and senescent cells (β-galactosidase staining), as well as a two-step euglycemic, pancreatic clamp with a stable-isotope labeled precursor ((U-13C)palmitate) infusion to determine the insulin concentration needed to suppress palmitate flux by 50% (IC50(palmitate)f).

Being tested
Omega-3, placebo
Medical subject headings
Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Omega-3Drug

    Also called Essential fatty acids, Omega-3 fatty acids, Omega-3 polyunsaturated fatty acids, PUFAs

    Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.

  • placeboDrug

Study groups in NCT01686568
Study groupRoleWhat they receive
Omega-3ExperimentalPatients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Receives: Drug: Omega-3
PlaceboPlacebo comparatorPatients in this group will be supplemented with placebo capsules containing ethyl oleate.
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, after 6 months of treatment

Secondary outcomes (6)

  1. 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.

    Measured: baseline, after 6 months of treatment

  2. 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.

    Measured: Baseline, after 6 months of treatment

  3. Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)

    Sensitivity of adipose tissue lipolysis to insulin suppression, was calculated as the insulin concentration needed to suppress palmitate appearance rates (ie, flux) by 50% (IC50(palmitate)f).

    Measured: approximately after 6 months of treatment

  4. Senescent Cells

    Tissue burden of senescent cells, which was measured by staining for senescence-associated B-galactosidase activity and expressed as the number per 100 nucleated positive cells.

    Measured: approximately after 6 months of treatment

  5. Immunohistochemistry Assessments of Macrophage Burden

    One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess macrophage burden (total (CD68), M1 (CD14) and M2 (CD206) macrophages per 100 adipocytes).

    Measured: approximately after 6 months of treatment

  6. Macrophage Crown-like Structures

    Macrophages surrounding dying or dead adipocytes form crown-like structures (CLSs). One week after the pancreatic clamp study, participants were provided a standardized meal before an overnight fast. The next morning an abdominal adipose tissue biopsy was collected, and the samples were analyzed for adipocyte size. Immunohistochemistry was used to assess the number of crown-like structures per 10 images.

    Measured: approximately after 6 months of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Sep 2012 (estimated)
  2. Study start21 Dec 2012
  3. Primary completion30 Oct 2014
  4. Study completion8 Jun 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01686568
Sponsor's protocol ID
12-004590
Other IDs
KL2TR000136, U24DK100469, DK50456, DK40484, 5T32DK007352, 5UL1TR000135
Status last verified
Jan 2017
First submitted
11 Sep 2012
Last updated
3 Mar 2017
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 25852206

  • Hames KC, Morgan-Bathke M, Harteneck DA, Zhou L, Port JD, Lanza IR, Jensen MD. Very-long-chain omega-3 fatty acid supplements and adipose tissue functions: a randomized controlled trial. Am J Clin Nutr. 2017 Jun;105(6):1552-1558. doi: 10.3945/ajcn.116.148114. Epub 2017 Apr 19.

    PubMed 28424185

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Omega-3 in people with Insulin Resistance, run by Mayo Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Jul 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up (time frame: Baseline, after 6 months of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01686568, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2017.

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