RESOLving INflammation Through Diet for Health (RESOLVIN)

NCT07331103 | Recruiting DMC

• 2 other identifiers: HORIZON-HLTH-2022-STAYHLTH-02HORIZON-HLTH-2022- STAYHLTH-02
• Study Type: interventional
• Target: 324
• Locations: 1 country
• Sites: 5

Brief 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),

Conditions

Cardiovascualr Disease; Inflammation; n-3 Polyunsatured Fatty Acids (n-3 PUFA); Lipids

Keywords

ASCVD; n-3 polyunsatured fatty acids; lipid driven/regulated vascular inflammation; n-3 PUFA; DHA; EPA; ALA

Outcome Measures

Primary Outcomes (2)

• the effect on a lipidomic/inflammation- derived risk score based on plasma biomarkers

  to compare the effect on a lipid/inflammation-derived risk scoremoderate= 50-69 years: 5 to 10%; \>70 years: 7.5 to \<15%; high=50-69 years: \>10%; 70 years \>15%), based on circulating molecules, of diets enriched with PUFA of animal or vegetal origin with a non-enriched diet.

  up to 12 weeks

• Primary objective

  The primary endpoint is to compare the effect on a lipidomic/inflammation-derived risk score based on plasma biomarkers, of diets with supplementation with PUFA of animal or vegetal origin with a non-enriched diet.

  18 months

Study Arms (3)

Fish oil

ACTIVE COMPARATOR

A total daily volume of 23.19 mL/day of fish oil.

Dietary Supplement: Fish Oil

Camelina Sativa Oil

ACTIVE COMPARATOR

a total volume of 30 mL/day + Vitamin E 24 mg.

Dietary Supplement: Camelina oil

Control

ACTIVE COMPARATOR

regular non-enriched diet + Vitamin E 24 mg

Dietary Supplement: Vitamin E

Interventions

Fish Oil DIETARY_SUPPLEMENT

2262.5 mg DHA plus 1739.1 mh EPA

Fish oil

Camelina oil DIETARY_SUPPLEMENT

10g/day of ALA for a total volume of 30 mL/day

Camelina Sativa Oil

Vitamin E DIETARY_SUPPLEMENT

a dose of 24 mg for the control group

Control

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are subjects \>55 y old from both sexes (\>=40% women) with moderate to high cardiovascular risk (ANNEX 1: SCORE2, SCORE2-OP and SCORE2-Diabetes assessment).

You may not qualify if:

• 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),
• 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.

Sponsors & Collaborators

• Mario Negri Institute for Pharmacological Research: lead

Study Sites (5)

Dr. Antonella Todesca

Avellino, AV, 83036, Italy

NOT YET RECRUITING

Dr. Tommaso Reginato

Arese, MI, 20044, Italy

RECRUITING

Istituto di Ricerche Farmacologiche Mario Negri

Milan, MI, 20156, Italy

RECRUITING

Dr. Giosafatte Zappia

Paderno Dugnano, MI, 20037, Italy

NOT YET RECRUITING

Ospedale Madonna delle Grazie Matera

Matera, MT, 75100, Italy

NOT YET RECRUITING

Related Publications (5)

• Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Lancet. 1999 Aug 7;354(9177):447-55.

  PMID: 10465168 BACKGROUND

• Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, Fonseca F, Nicolau J, Koenig W, Anker SD, Kastelein JJP, Cornel JH, Pais P, Pella D, Genest J, Cifkova R, Lorenzatti A, Forster T, Kobalava Z, Vida-Simiti L, Flather M, Shimokawa H, Ogawa H, Dellborg M, Rossi PRF, Troquay RPT, Libby P, Glynn RJ; CANTOS Trial Group. Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease. N Engl J Med. 2017 Sep 21;377(12):1119-1131. doi: 10.1056/NEJMoa1707914. Epub 2017 Aug 27.

  PMID: 28845751 BACKGROUND

• Tunon J, Badimon L, Bochaton-Piallat ML, Cariou B, Daemen MJ, Egido J, Evans PC, Hoefer IE, Ketelhuth DFJ, Lutgens E, Matter CM, Monaco C, Steffens S, Stroes E, Vindis C, Weber C, Back M. Identifying the anti-inflammatory response to lipid lowering therapy: a position paper from the working group on atherosclerosis and vascular biology of the European Society of Cardiology. Cardiovasc Res. 2019 Jan 1;115(1):10-19. doi: 10.1093/cvr/cvy293.

  PMID: 30534957 BACKGROUND

• Visseren FLJ, Mach F, Smulders YM, Carballo D, Koskinas KC, Back M, Benetos A, Biffi A, Boavida JM, Capodanno D, Cosyns B, Crawford C, Davos CH, Desormais I, Di Angelantonio E, Franco OH, Halvorsen S, Hobbs FDR, Hollander M, Jankowska EA, Michal M, Sacco S, Sattar N, Tokgozoglu L, Tonstad S, Tsioufis KP, van Dis I, van Gelder IC, Wanner C, Williams B; ESC National Cardiac Societies; ESC Scientific Document Group. 2021 ESC Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2021 Sep 7;42(34):3227-3337. doi: 10.1093/eurheartj/ehab484. No abstract available.

  PMID: 34458905 BACKGROUND

• Back M, Yurdagul A Jr, Tabas I, Oorni K, Kovanen PT. Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities. Nat Rev Cardiol. 2019 Jul;16(7):389-406. doi: 10.1038/s41569-019-0169-2.

  PMID: 30846875 BACKGROUND

MeSH Terms

Conditions

Inflammation

Interventions

Fish Oils; Vitamin E

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Oils; Lipids; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jennifer Meessen, phD

  Laboratory Clinical Research in Brain and Cardiovascular Injury Istituto di Ricerche Farmacologiche Mario Negri IRCCS

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marianna Cerrato, phD

CONTACT

+39 023901414617; marianna.cerrato@marionegri.it

Antonella Vasamì, High school diploma

CONTACT

+39 023901414450; antonella.vasami@marionegri.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Multicenter, prospective randomized, controlled and open- label

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: January 9, 2026
• Study Start: November 26, 2025
• Primary Completion: March 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (5)