Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| KL2TR000136 | U.S. NIH Grant/Contract | View source | |
| U24DK100469 | U.S. NIH Grant/Contract | View source | |
| DK50456 | Other Grant/Funding Number | Minnesota Obesity Center | |
| DK40484 | Other Grant/Funding Number | Minnesota Obesity Center | |
| 5T32DK007352 | U.S. NIH Grant/Contract | View source | |
| 5UL1TR000135 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Center for Advancing Translational Sciences (NCATS) | NIH |
| National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) | NIH |
| Building Interdisciplinary Research Careers in Women's Health |
Not provided
Not provided
Not provided
Not provided
This study is being done to understand the effects of dietary omega-3 fats on insulin sensitivity in adult men and women.
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).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Omega-3 | Experimental | Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. |
|
| Placebo | Placebo Comparator | Patients in this group will be supplemented with placebo capsules containing ethyl oleate. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Omega-3 | Drug | Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Not provided
Inclusion criteria:
Exclusion criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Ian Lanza, PhD | Mayo Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mayo Clinic in Rochester | Rochester | Minnesota | 55905 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25852206 | Result | 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. | |
| 28424185 | Derived | 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. |
Not provided
Not provided
Not provided
Participants were recruited from the Mayo Clinic in Rochester, Minnesota.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Omega-3 | Patients in this group will receive oral supplementation with EPA + Docosahexaenoic acid (DHA) (3.9grams/day) for 6 months. |
| FG001 | Placebo | Patients in this group will be supplemented with placebo capsules containing ethyl oleate. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Main Study |
|
| |||||||||||||||||||||
| Sub-Study |
|
Baseline characteristics were reported for participants who received treatment and did not withdraw from the study.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Omega-3 | Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. |
| BG001 | Placebo | Patients in this group will be supplemented with placebo capsules containing ethyl oleate. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Error | mg/kg FFM/min | Baseline, after 6 months of treatment |
|
6 months
Not provided
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Omega-3 | Patients in this group will receive oral supplementation with EPA+DHA (3.9grams/day) for 6 months. |
Not provided
Not provided
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Ian R. Lanza | Mayo Clinic | 507-255-8147 | lanza.ian@mayo.edu |
Not provided
| ID | Term |
|---|---|
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D006946 | Hyperinsulinism |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D004281 | Docosahexaenoic Acids |
| D005228 | Fatty Acids, Essential |
| D015525 | Fatty Acids, Omega-3 |
| C405603 | Omacor |
| ID | Term |
|---|---|
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| placebo | Drug |
|
| 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 |
| 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). | approximately after 6 months of treatment |
| 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. | approximately after 6 months of treatment |
| 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). | approximately after 6 months of treatment |
| 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. | approximately after 6 months of treatment |
| Liver enzymes above range of exclusion |
|
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Placebo | Patients in this group will be supplemented with placebo capsules containing ethyl oleate. |
|
|
| 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. | Posted | Mean | Standard Error | nmol/L | baseline, after 6 months of treatment |
|
|
|
| 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. | Posted | Mean | Standard Error | pmol/s/mg tissue | Baseline, after 6 months of treatment |
|
|
|
| Secondary | 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). | 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. | Posted | Median | Inter-Quartile Range | µU/mL | approximately after 6 months of treatment |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | number positive cells/100 total cells | approximately after 6 months of treatment |
|
|
|
| Secondary | 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). | Posted | Mean | Standard Deviation | macrophages per 100 adipocytes | approximately after 6 months of treatment |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | crown-like structures per 10 images | approximately after 6 months of treatment |
|
|
|
| Post-Hoc | EPA and DHA Concentrations in Plasma | 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. | Posted | Mean | Standard Error | percentage of total free fatty acid | approximately after 6 months of treatment |
|
|
|
| Post-Hoc | EPA and DHA Concentrations in Adipose Tissue | 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. | Posted | Mean | Standard Error | percentage of total free fatty acid | approximately after 6 months of treatment |
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| EG001 | Placebo | Patients in this group will be supplemented with placebo capsules containing ethyl oleate. | 0 | 11 | 0 | 11 |
Not provided
Not provided
Not provided
| D005231 |
| Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |
| M1 (CD14) baseline |
|
| M1 (CD14) post intervention |
|
| M2 (CD206) baseline |
|
| M2 (CD206) post intervention |
|
| DHA Baseline |
|
| DHA Post-Intervention |
|
| DHA Baseline |
|
| DHA Post-Intervention |
|