The Effect of Oral SPM Supplementation on INflammation-induced Vascular Ageing in Obese Hypertensive Patients

Обзор

Cardiovascular risk factors such as obesity, diabetes, high blood pressure, high cholesterol, or smoking are associated with an increased risk of events such as myocardial infarction, stroke, or peripheral artery disease. Lifestyle and dietary measures, as well as pharmacological treatments, can help correct these risk factors. However, several studies have shown that even with optimal treatment, individuals at high risk still face a residual cardiovascular risk. This phenomenon is primarily attributed to the development of vascular lesions, meaning damage within the blood vessels. These lesions are largely due to inflammation, an activated immune state that is more pronounced in overweight individuals and significantly contributes to vascular damage, potentially shortening the lifespan of those with cardiovascular disease. Although anti-inflammatory therapies have proven effective in reducing this risk, they may interfere with tissue repair and the immune system. For this reason, it is essential to identify strategies that promote the resolution of inflammation without compromising these vital processes. Specialized pro-resolving mediators (SPMs) are compounds derived from omega-3 and omega-6 polyunsaturated fatty acids, which are naturally found in various foods such as fish. These mediators help limit the infiltration of inflammatory cells and initiate the repair of damaged tissues. This type of dietary supplement is already available over the counter, but its health benefits have not been extensively studied. Experimental animal studies have shown that restoring inflammation resolution through SPMs can prevent-or even reverse-cardiovascular damage and inflammation by directly acting on vascular cells and modulating the immune system. However, human data on the role of SPMs and inflammation resolution in vascular disease remain very limited. The investigators hypothesize that in individuals at high cardiovascular risk (due to obesity and hypertension), increasing circulating levels of SPMs through oral supplementation (as a dietary supplement) would improve vascular function, metabolic profile, and inflammatory and immune cell responses. In doing so, this may help reduce the residual risk of cardiovascular disease. The objective of this research is to assess whether a supplement enriched with SPMs can facilitate the resolution of inflammation, which is essential for restoring vascular function and thereby supporting the body's natural tissue repair mechanisms. To address the research question, the study plans to include 60 individuals with obesity and hypertension, all presenting a high cardiovascular risk, recruited from healthcare facilities located in France. This research is publicly funded by the French National Research Agency (Agence Nationale de la Recherche) through the European research project RESPIN-VAR, co-funded by ERA4Health and the European Union.

Вмешательства

• Пищевая добавка Oral SPM-enriched marine oil (LIPINOVA)
  LIPINOVA is an oral dietary supplement provided by Solutex, consisting of marine oil enriched in specialized pro-resolving mediator (SPM) precursors. Each daily dose (3 g/day) includes 1500 mg of omega-3 free fatty acids and a minimum of 520 mcg of SPM precursors (17-HDHA, 18-HEPE, 14-HDHA). The supplement is administered orally in 6 softgel capsules per day (3 after breakfast, 3 after dinner) over 12 weeks. It is used to investigate its effect on vascular function and inflammation in patients w
• Пищевая добавка Placebo
  Placebo capsules provided by Solutex, identical in appearance to LIPINOVA, contain refined olive oil with no active omega-3 fatty acids or SPM precursors. The placebo is administered orally in 6 softgel capsules per day (3 after breakfast, 3 after dinner) for 12 weeks, following a randomized, double-blind, crossover design. It serves as a control to evaluate the effects of SPM-enriched marine oil on vascular and inflammatory parameters in patients with obesity-related hypertension.

Первичные конечные точки

• Flow-mediated dilation (FMD) [Срок оценки: FMD will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 14 (after a wash-out period of 2 weeks ± 2 days), Week 26 (after a second administration period of 12 weeks ± 2 days)]

Вторичные конечные точки (12)

• Shear rate area under the curve (SR-AUC) [Срок оценки: These parameters will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 14 (after a wash-out period of 2 weeks ± 2 days), Week 26 (after a second administration period of 12 weeks ± 2 days)]
• Difference after 12 -week- intervention with oral SPM supplementation or placebo in arterial stiffness [Срок оценки: These parameters will be measured at Week 0 (baseline), Week 12 (after a first administration period of 12 weeks ± 2 days) , Week 14 (after a wash-out period of 2 weeks ± 2 days), Week 26 (after a second administration period of 12 weeks ± 2 days)]
• Change from initiation to the end of the 12 -week- intervention in endothelial injury [Срок оценки: These parameters will be measured at Week 0 (baseline), Week 12, Week 14, Week 26.]
• Change from initiation to the end of the 12 -week- intervention immune cell profile [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Insulin sensitivity [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Change in Body Fat Mass [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Change in Lipid profile [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Safety assessement by Liver function markers [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Safety assessement by Renal function markers [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Safety assessement by Coagulation markers [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• SPM levels [Срок оценки: These parameters will be measured at Week 0, Week12, Week14, Week26]
• Questionnaires about perceptions and expectations about oral supplements for cardiovascular disease prevention [Срок оценки: Week 0 and Week 26]

Критерии участия

Критерии включения

• Age between 18 and 85 years,.
• Hypertension controlled under pharmacological or non-pharmacological treatment, defined as office BP< 140/90 mmHg at the Inclusion visit,
• BMI > 30 kg/m²,
• Stable antihypertensive treatment one month before inclusion (V1),
• Signed informed consent,
• Social security affiliation.

Критерии исключения

• Secondary hypertension on the basis of medical history,
• History of stroke in the previous 6 months on the basis of medical history,
• Myocardial infarction in the previous 6 months on the basis of medical history,
• Severe hepatic insufficiency on the basis of medical history,
• Chronic kidney disease (DFG < 30 ml/min 1.73 according to MDRD method),
• Pregnancy or breast feeding,
• Regular treatment with NO-donors or phosphodiesterase inhibitors,
• Inability to comply with protocol requirements,
• Patient under tutorship or / guardianship or/ safeguard of justice, and incapable to give informed consent,
• Patient on AME (state medical aid),
• Participation in another interventional study involving human participants ,
• Allergy to the ultrasound gel,
• Hypersensitivity , allergy, or idiosyncratic reaction to omega-3 acids, fish or soya allergies.
• Chronic inflammatory diseases, on the basis of medical history,
• Chronic anti-inflammatory treatment administered within the past month preceding the Inclusion visit,
• Any supplementation with omega-3 or omega-6 polyunsaturated fatty acids within the past month,
• Life expectancy less than one year.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Франция · 1 центр

• Service de Pharmacologie - UF Pharmacologie Clinique — Paris

Идентификаторы

NCT: NCT07038252 · APHP241105 · 2025-A00108-41

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗