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Omega-3 Fatty Acids and Insulin Sensitivity

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ClinicalTrials.gov Identifier: NCT01686568
Recruitment Status : Completed
First Posted : September 18, 2012
Results First Posted : July 10, 2015
Last Update Posted : March 3, 2017
Sponsor:
Collaborators:
National Center for Advancing Translational Science (NCATS)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Building Interdisciplinary Research Careers in Women's Health
Information provided by (Responsible Party):
Ian R. Lanza, Mayo Clinic

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Insulin Resistance
Interventions Drug: Omega-3
Drug: placebo
Enrollment 31
Recruitment Details Participants were recruited from the Mayo Clinic in Rochester, Minnesota.
Pre-assignment Details  
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description Patients in this group will receive oral supplementation with EPA + Docosahexaenoic acid (DHA) (3.9grams/day) for 6 months. Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Period Title: Main Study
Started 16 15
Completed 14 11
Not Completed 2 4
Reason Not Completed
Withdrawal by Subject             1             3
Noncompliance with protocol             0             1
Liver enzymes above range of exclusion             1             0
Period Title: Sub-Study
Started 14 11
Completed 12 9
Not Completed 2 2
Reason Not Completed
Not consented for sub-study             2             2
Arm/Group Title Omega-3 Placebo Total
Hide Arm/Group Description Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. Patients in this group will be supplemented with placebo capsules containing ethyl oleate. Total of all reporting groups
Overall Number of Baseline Participants 14 11 25
Hide Baseline Analysis Population Description
Baseline characteristics were reported for participants who received treatment and did not withdraw from the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 11 participants 25 participants
35.3  (2.9) 32.6  (2.5) 34.1  (9.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 11 participants 25 participants
Female
9
  64.3%
9
  81.8%
18
  72.0%
Male
5
  35.7%
2
  18.2%
7
  28.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 14 participants 11 participants 25 participants
14 11 25
1.Primary Outcome
Title Insulin Sensitivity by Hyperinsulinemic-euglycemic Clamp at Baseline and 6 Month Follow up
Hide Description 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.
Time Frame Baseline, after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 14 11
Mean (Standard Error)
Unit of Measure: mg/kg FFM/min
Baseline 10.92  (1.04) 10.39  (0.76)
6 Month Follow Up 10.16  (1.02) 10.80  (0.73)
2.Secondary Outcome
Title Beta Cell Function From Insulin Secretion Following Ingestion of a Mixed Meal at Baseline and 6 Month Follow up
Hide Description 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.
Time Frame baseline, after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 14 11
Mean (Standard Error)
Unit of Measure: nmol/L
Baseline 537.17  (45.33) 488.90  (45.47)
6 Month Follow Up 561.33  (48.21) 504.39  (35.93)
3.Secondary Outcome
Title Mitochondrial Function Determined by Muscle Biopsy at Baseline and 6 Month Follow up
Hide Description Measurements of oxygen consumption in isolated mitochondria will be performed using a polarographic oxygen electrode.
Time Frame Baseline, after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 14 11
Mean (Standard Error)
Unit of Measure: pmol/s/mg tissue
Baseline 496.81  (26.54) 564.86  (42.10)
6 Month Follow Up 406.38  (40.39) 495.12  (39.79)
4.Secondary Outcome
Title Insulin Concentration Needed to Suppress Palmitate Appearance Rates (IC50(Palmitate)f)
Hide Description 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).
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The number of subjects analyzed for this outcome measure for the placebo arm was 8 instead of 9. One subject did not have blood drawn for this outcome measure.
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 8
Median (Inter-Quartile Range)
Unit of Measure: µU/mL
Baseline
22
(13 to 24)
25
(22 to 33)
Post-intervention
18
(16 to 29)
19
(14 to 46)
5.Secondary Outcome
Title Senescent Cells
Hide Description 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.
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 9
Mean (Standard Deviation)
Unit of Measure: number positive cells/100 total cells
Baseline 4  (3) 4  (3)
Post-intervention 4  (3) 4  (2)
6.Secondary Outcome
Title Immunohistochemistry Assessments of Macrophage Burden
Hide Description 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).
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 9
Mean (Standard Deviation)
Unit of Measure: macrophages per 100 adipocytes
Total (CD68) baseline 31  (8) 33  (5)
Total (CD68) post intervention 33  (8) 31  (5)
M1 (CD14) baseline 11  (6) 13  (4)
M1 (CD14) post intervention 14  (6) 12  (5)
M2 (CD206) baseline 28  (5) 29  (7)
M2 (CD206) post intervention 29  (9) 29  (5)
7.Secondary Outcome
Title Macrophage Crown-like Structures
Hide Description 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.
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 9
Median (Inter-Quartile Range)
Unit of Measure: crown-like structures per 10 images
Baseline
0
(0 to 1)
1
(0 to 3)
Post-intervention
0
(0 to 1)
1
(0 to 2)
8.Post-Hoc Outcome
Title EPA and DHA Concentrations in Plasma
Hide Description Post hoc analyses were conducted to test whether EPA and DHA concentrations in plasma in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 9
Mean (Standard Error)
Unit of Measure: percentage of total free fatty acid
EPA Baseline 0.95  (0.22) 1.2  (0.27)
EPA Post-Intervention 6.0  (0.92) 1.1  (0.19)
DHA Baseline 0.89  (0.23) 1.2  (0.39)
DHA Post-Intervention 3.5  (0.84) 0.90  (0.18)
9.Post-Hoc Outcome
Title EPA and DHA Concentrations in Adipose Tissue
Hide Description Post hoc analyses were conducted to test whether EPA and DHA concentrations in subcutaneous abdominal adipose tissue in response to intervention explained variation in outcome measures of adipose tissue lipolysis insulin sensitivity and inflammatory markers post-intervention.
Time Frame approximately after 6 months of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description:
Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months.
Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
Overall Number of Participants Analyzed 12 9
Mean (Standard Error)
Unit of Measure: percentage of total free fatty acid
EPA baseline 0.06  (0.00) 0.07  (0.01)
EPA Post-Intervention 0.19  (0.02) 0.07  (0.01)
DHA Baseline 0.14  (0.01) 0.15  (0.01)
DHA Post-Intervention 0.28  (0.02) 0.16  (0.02)
Time Frame 6 months
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Omega-3 Placebo
Hide Arm/Group Description Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. Patients in this group will be supplemented with placebo capsules containing ethyl oleate.
All-Cause Mortality
Omega-3 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Omega-3 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)   0/11 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Omega-3 Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/14 (0.00%)   0/11 (0.00%) 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Dr. Ian R. Lanza
Organization: Mayo Clinic
Phone: 507-255-8147
EMail: lanza.ian@mayo.edu
Layout table for additonal information
Responsible Party: Ian R. Lanza, Mayo Clinic
ClinicalTrials.gov Identifier: NCT01686568     History of Changes
Other Study ID Numbers: 12-004590
KL2TR000136 ( U.S. NIH Grant/Contract )
U24DK100469 ( U.S. NIH Grant/Contract )
DK50456 ( Other Grant/Funding Number: Minnesota Obesity Center )
DK40484 ( Other Grant/Funding Number: Minnesota Obesity Center )
5T32DK007352 ( U.S. NIH Grant/Contract )
5UL1TR000135 ( U.S. NIH Grant/Contract )
First Submitted: September 11, 2012
First Posted: September 18, 2012
Results First Submitted: June 16, 2015
Results First Posted: July 10, 2015
Last Update Posted: March 3, 2017