Clinical Trials Logo

Clinical Trial Summary

In this project, investigators explored the role of the particles that carry "bad cholesterol" in the blood (termed LDL) that are known to promote heart disease, in the promotion of type 2 diabetes (T2D) in humans. In specific, they investigated how these particles may induce the activation of an immune pathway in human fat tissue leading to multiple anomalies that favors T2D. They also explored whether omega-3 fatty acids, which are the type of fat found in fish oils can counterbalance the negative effects of LDL in fat tissue, thus providing a natural way to help reduce the risk for T2D in subjects with elevated blood LDL. To do so, 41 subjects who were free of disease or medication affecting metabolism were enrolled at the Montreal Clinical Research Institute between 2013 and 2019 and were placed on an intervention with omega-3 fatty acids supplementation for 12 weeks (2.7 g/day, Triple Strength Omega-3 from Webbers Naturals). Investigators examined the effects of LDL and omega-3 on risk factors for T2D before and after the intervention in the whole body and specifically in fat tissue biopsies taken from the hip region. Eighty percent of the subjects who were enrolled into the study completed the intervention.


Clinical Trial Description

Diabetes-attributed deaths, mostly type 2 diabetes (T2D), total more than 40,000 per year, out of which 80% are secondary to cardiovascular disease and stroke. Research from the investigators' lab and others suggests that elevated atherogenic apoB-lipoproteins, mostly low-density lipoproteins (LDL) may not be a mere consequence of T2D but also a cause. They reported that high numbers of apoB-lipoproteins (apoB) induce subcutaneous white adipose tissue (WAT) dysfunction and predict several risk factors for T2D in humans. However, mechanisms underlying LDL-induced abnormalities and nutritional approaches to target them remain unexplored. Strong evidence implicates a specific innate immunity system, the NLRP3 inflammasome/ interleukin 1 beta (IL-1β) pathway in WAT dysfunction and associated T2D risk factors in mice and humans (NLRP3 for Nucleotide-binding domain and Leucine-rich repeat Receptor, containing a Pyrin domain 3). Preliminary evidence from the investigator's lab and their collaborator (Dr Maya Saleh, at McGill University) indicated that native apoB-lipoproteins activate the NLRP3 inflammasome leading to IL-1β secretion in murine bone marrow derived macrophages. On the other hand, fish-oil derived omega-3 fatty acids, eicosapentaenoic and docosahexaenoic acids (EPA and DHA), were reported to inhibit the NLRP3 inflammasome/ IL-1β pathway in immune cells. Thus, the central hypothesis of this trial was that apoB-lipoproteins act as metabolic danger-associated molecular patterns that activate the NLRP3 inflammasome in WAT leading to WAT dysfunction and associated risks for T2D in humans. This can be treated by EPA and DHA supplementation. The specific hypotheses examined in 2 parts of this trial, at baseline and post-intervention, were: Part A: At baseline (mechanisms): Primary hypothesis: 1. Compared to subjects with low plasma apoB, subjects with high plasma apoB have higher WAT NLRP3 inflammasome activity indicated by higher WAT IL-1β secretion. Secondary hypotheses: 2. WAT IL-1β secretion is associated with risk factors for T2D (WAT dysfunction, systemic inflammation, postprandial hypertriglyceridemia, insulin resistance and hyperinsulinemia). 3. Ex vivo, subjects' native LDL prime and/or activate the NLRP3 inflammasome in subjects' own WAT. Part B: Post-intervention (treatment of the baseline mechanisms): Primary hypothesis: 1. Compared to subjects with low plasma apoB, twelve-week supplementation with EPA and DHA induces a greater reduction in WAT IL-1β secretion in subjects with high plasma apoB eliminating baseline group-differences. Secondary hypotheses: 2. Compared to subjects with low plasma apoB, twelve-week supplementation with EPA and DHA induces a greater reduction in risk factors for T2D in subjects with high plasma apoB. 3. Twelve-week supplementation with EPA and DHA reduces the baseline associations of WAT IL-1β secretion with risk factors for T2D 4. Ex vivo, EPA and DHA inhibit LDL-induced priming and/or activation of subjects' WAT NLRP3 inflammasome. Forty-one subjects (34% men) were enrolled in the study, of whom 33 subjects completed the 12-week omega-3 intervention (drop out/exclusion rate = 20%). For statistical analysis, subjects were stratified into 2 groups based on baseline median plasma apoB per sex. The 2 groups with high plasma apoB and low plasma apoB were characterized and compared for the primary and secondary outcomes at baseline and following the omega-3 intervention. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04496154
Study type Interventional
Source Institut de Recherches Cliniques de Montreal
Contact
Status Completed
Phase N/A
Start date September 5, 2013
Completion date February 24, 2020

See also
  Status Clinical Trial Phase
Completed NCT05219994 - Targeting the Carotid Bodies to Reduce Disease Risk Along the Diabetes Continuum N/A
Completed NCT04056208 - Pistachios Blood Sugar Control, Heart and Gut Health Phase 2
Completed NCT02284893 - Study to Evaluate the Efficacy and Safety of Saxagliptin Co-administered With Dapagliflozin in Combination With Metformin Compared to Sitagliptin in Combination With Metformin in Adult Patients With Type 2 Diabetes Who Have Inadequate Glycemic Control on Metformin Therapy Alone Phase 3
Completed NCT04274660 - Evaluation of Diabetes and WELLbeing Programme N/A
Active, not recruiting NCT05887817 - Effects of Finerenone on Vascular Stiffness and Cardiorenal Biomarkers in T2D and CKD (FIVE-STAR) Phase 4
Active, not recruiting NCT05566847 - Overcoming Therapeutic Inertia Among Adults Recently Diagnosed With Type 2 Diabetes N/A
Recruiting NCT06007404 - Understanding Metabolism and Inflammation Risks for Diabetes in Adolescents
Completed NCT04965506 - A Study of IBI362 in Chinese Patients With Type 2 Diabetes Phase 2
Recruiting NCT05979779 - Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Obese Subjects With Type 2 Diabetes at Risk of Nonalcoholic Steatohepatitis Phase 2
Recruiting NCT06115265 - Ketogenic Diet and Diabetes Demonstration Project N/A
Active, not recruiting NCT03982381 - SGLT2 Inhibitor or Metformin as Standard Treatment of Early Stage Type 2 Diabetes Phase 4
Completed NCT04971317 - The Influence of Simple, Low-Cost Chemistry Intervention Videos: A Randomized Trial of Children's Preferences for Sugar-Sweetened Beverages N/A
Completed NCT04023539 - Effect of Cinnamomum Zeylanicum on Glycemic Levels of Adult Patients With Type 2 Diabetes N/A
Recruiting NCT05572814 - Transform: Teaching, Technology, and Teams N/A
Enrolling by invitation NCT05530356 - Renal Hemodynamics, Energetics and Insulin Resistance: A Follow-up Study
Completed NCT03960424 - Diabetes Management Program for Hispanic/Latino N/A
Completed NCT04097600 - A Research Study Comparing Active Drug in the Blood in Healthy Participants Following Dosing of the Current and a New Formulation (D) Semaglutide Tablets Phase 1
Completed NCT05378282 - Identification of Diabetic Nephropathy Biomarkers Through Transcriptomics
Recruiting NCT06010004 - A Long-term Safety Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes Phase 3
Completed NCT03653091 - Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes N/A