Clinical Research Directory

RESOLving INflammation Through Diet for Health (RESOLVIN)

Sponsor: Mario Negri Institute for Pharmacological Research

Summary

Hyperlipidemia is the main driver of atherosclerotic cardiovascular disease (ASCVD), both through direct effects and as trigger of the chronic inflammation behind a cardiovascular health-to-disease transition. While lipid-lowering is an effective way to reduce the ASCVD risk, the residual risk remains high. In addition, a substantial proportion of ASCVD events occur in the absence of overt hyperlipidemia. Several lines of evidence ranging from experimental models to population studies and interventional clinical trials support chronic inflammation as the causal residual risk of CVD. The CVD risk-associated lipid classes contain fatty acids that can be liberated and metabolized into both inflammation-promoting as well as inflammation-resolving drivers, providing the rationale for focusing on this balance in the present project. Above all, the omega-3 fatty acid class can resolve inflammation but the potential impact is currently largely underestimated in CVD preventive recommendations. As cardiovascular preventive measures ease the burden placed on the individual, population, and on the health care system, it is critical to raise public awareness for chronic inflammation as a causative and modifiable cardiovascular risk factor and to provide tools for how to control and monitor it. As an alternative to marine sources, principally eicosapentaenoic acid (EPA) and less docosahexaenoic acid (DHA) can be endogenously produced from alpha-linolenic acid (ALA) found in plant oils. Secondarily the possibility to increase the consumption of vegetable oil may possibly decrease the environmental impacts of an intensive fishing and consecutive marine system imbalance. The overarching objective of CARE-IN-HEALTH is to assess if PUFAs may contribute to the resolution of the chronic lipid-driven/-regulated vascular inflammation in order to develop and test, in a real-life setting, tools for use in health care and by citizens to stay healthy by an adequate resolution of the chronic inflammation. The primary objective of the present study is to compare the effect on a lipid/inflammation-derived risk score of diets supplemented with polyunsaturated fatty acids (PUFA) of animal or vegetal origin with a nonenriched diet. The secondary objectives are a) to assess the acceptance of supplementation of diet with animal-derived or plant-derived PUFAs; b) to improve circulating lipid, inflammatory glycemic profile based on serial measurements of circulating biomarkers by means of PUFA supplementation. The study aims to identify a blueprint for how to control lipid-driven chronic inflammation by simple dietary interventions. Study population Participants to be considered for eligibility in the trial are adults aged \>55 y, of both sexes (\>=40% women), at moderate to high cardiovascular risk. The inclusion criteria are: Eligible participants will be at moderate to high SCORE2, SCORE2-OP and SCORE2-Diabetes risk level. Non-eligible subjects will be those with: * cardiovascular disease, * established atherosclerotic vascular disease involving the coronary, peripheral, carotid, or aortic territories (identified by computerized tomography (CT) of coronary arteries, MRI, carotid or peripheral ultrasound imaging), * chronic treatment with n-3 PUFA containing products (i.e., Vazkepa) or fibrates, * a condition that interferes with the possibility to follow the dietary intervention, such as fish allergy or being a vegan, * significant liver dysfunction, * participation in another intervention clinical study. Participants will be centrally randomized by a web-based system to one of the 3 diets: 1) supplementation with 4 grams n-3 PUFAs (containing 2262.5 mg DHA plus 1739.1 mg EPA), 2) diet enriched with n-3 PUFAs of vegetable origin (Camelina Sativa Oil) + vitamin E 24 mg, and 3) regular uncontrolled diet + vitamin E 24 mg. The daily intake of 10 grams of ALA for participants randomized to Camelina Sativa Oil is equivalent to approximately 1500 mg of n-3 PUFAs. Fish oil and Camelina Sativa oil will be administered as liquid oils for the duration of 12 weeks. The addition of vitamin E is aimed at supplementing the same amount of this vitamin to participants. Eligible participants will undergo a clinical visit when also a blood sample will be taken at baseline and at 12 weeks follow-up. The main analysis will be performed according to a per protocol approach, therefore only participants compliant with study treatments will be included in the analysis. Primary objective: to compare the effect on a lipid/inflammation-derived risk score, based on circulating molecules, of diets enriched with PUFA of animal or vegetal origin with a non-enriched diet. Secondary objectives: a) to assess the acceptance of supplementation of diet with animal-derived or plant-derived PUFAs; b) to improve circulating lipidic/glycemic inflammatory profile. All 324 participants enrolled in the trial will have blood samples taken twice (at baseline and 12 weeks),

Official title: RESOLving INflammation Through Diet for Health Multicenter, Prospective Randomized, Controlled and Open- Label to Examine the Impact of a Diet Enriched in Omega 3 Fatty Acids of Animal and Vegetal Origin on Circulating Lipid-driven Pro-/Antiinflammatory Balance in Subjects at Moderate to High Cardiovascular Risk.

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