Functional Milk Supplementation to Reduce In-Stent Restenosis in STEMI Patients (SMASOEA Trial)

Official title

Effects of Functional Bovine Milk Supplementation on Coronary In-Stent Restenosis and Major Adverse Cardiovascular Events in STEMI Patients Undergoing Primary PCI: A Randomized, Double-Blind, Controlled Trial

Overview

This randomized, double-blind, controlled clinical trial will evaluate the effects of daily supplementation with functionalized bovine milk, enriched with bioactive peptides and optimized lipid profile, on coronary in-stent restenosis and major adverse cardiovascular events (MACE) in patients with first ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) and drug-eluting stent (DES) implantation. Participants will be randomly assigned to receive either functionalized milk or an isocaloric non-functional milk for 12 months, in addition to standard secondary prevention care. The primary endpoint is the incidence of in-stent restenosis at 12 months, assessed by coronary computed tomography angiography (CCTA). Secondary endpoints include MACE occurrence, metabolic and inflammatory biomarkers, oxidative stress markers, serum sirtuins, metabolomic profiles, and myocardial injury evaluated by cardiac positron emission tomography (PET). The study aims to determine whether functionalized milk can improve cardiovascular outcomes and modulate pathophysiological mechanisms after STEMI.

Detailed description

Coronary artery disease remains a leading cause of morbidity and mortality worldwide. Despite advances in percutaneous coronary intervention (PCI) and the use of drug-eluting stents (DES), in-stent restenosis (ISR) continues to occur, driven by neointimal hyperplasia, vascular inflammation, and metabolic dysregulation. Nutritional interventions with specific bioactive compounds may offer an innovative adjunct to secondary prevention strategies.

This investigator-initiated, randomized, double-blind, controlled trial will assess whether functionalized bovine milk (FM) - standardized to contain a defined profile of bioactive peptides with antihypertensive, anti-thrombotic, anti-inflammatory, antioxidant, and plaque-stabilizing properties - can reduce ISR incidence and improve cardiovascular outcomes in patients with a first ST-elevation myocardial infarction (STEMI) treated with PCI and DES.

A total of 140 eligible patients will be randomized 1:1 to receive FM or an isocaloric non-functional milk (NFM) for 12 months, in addition to guideline-directed secondary prevention care. Both products will be organoleptically matched, blinded by coded packaging, and supplied in equal volumes.

The primary endpoint is the proportion of patients with ISR at 12 months, as measured by coronary computed tomography angiography (CCTA). Secondary endpoints include the composite of major adverse cardiovascular events (MACE: cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure), changes in insulin secretion and sensitivity, systemic inflammatory markers (hsCRP, IL-6, TNF-α), oxidative stress parameters, serum sirtuins, and metabolomic/lipidomic profiles obtained through LC-MS and GC-MS. Myocardial injury and viability will also be quantified by cardiac positron emission tomography (PET) at baseline and at study completion.

Adherence will be monitored through dietary records, packaging return counts, and optional biochemical markers. An independent Data Safety Monitoring Board (DSMB) will oversee patient safety and trial conduct. The study is powered to detect a 50% relative reduction in ISR (from 30% to 15%) with 80% power and a two-sided alpha of 0.05.

If positive, the trial will provide robust clinical evidence for the incorporation of a standardised functional dairy product into secondary prevention dietary guidelines for post-STEMI patients, potentially addressing both residual inflammatory risk and metabolic contributors to recurrent events.

Interventions

• Dietary supplement Functional Bovine Milk
  Functional milk product enriched with standardised bioactive peptides, provided daily for 12 months.
• Dietary supplement Non-Functional Bovine Milk
  Standard bovine milk with identical caloric and macronutrient profile to the functionalized milk, without enrichment, provided daily for 12 months.

Primary outcome measures

• Incidence of In-Stent Restenosis at 12 Months [Time frame: 12 months after PCI]
• Major Adverse Cardiovascular Events (MACE) [Time frame: 12 months after PCI]

Secondary outcome measures (8)

• Change in Inflammatory Biomarkers [Time frame: 12 months after PCI]
• Change in Oxidative Stress Parameters [Time frame: 12 months after PCI]
• Change in Serum Sirtuin Levels [Time frame: 12 months after PCI]
• Metabolomic Profile Changes [Time frame: 12 months after PCI]
• Cardiac PET Imaging Parameters [Time frame: 12 months after PCI]
• Change in inflammatory markers [Time frame: 12 months after PCIr PCI]
• Change in inflammatory markers [Time frame: 12 months after PCI]
• Change in Oxidative Stress parameters [Time frame: 12 months after PCI]

Eligibility criteria

Inclusion criteria

• Age 18-80 years
• First ST-elevation myocardial infarction (STEMI) treated with percutaneous coronary intervention (PCI) and drug-eluting stent implantation within the previous 4 weeks
• Stable clinical condition at enrollment
• Willingness to adhere to study procedures and dietary supplementation for 12 months
• Signed informed consent

Exclusion criteria

• Previous myocardial infarction or coronary revascularization
• Cardiogenic shock or severe heart failure (NYHA class IV)
• Severe renal impairment (eGFR <30 mL/min/1.73m²) or dialysis
• Active malignancy or life expectancy <1 year
• Known lactose intolerance or allergy to milk proteins
• Participation in another interventional clinical trial in the last 30 days

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Italy · 1 center

• Università degli Studi della Campania "Luigi Vanvitelli" - Dipartimento di Scienze Mediche — Naples

Publications

• Astrup A, Magkos F, Bier DM, Brenna JT, de Oliveira Otto MC, Hill JO, King JC, Mente A, Ordovas JM, Volek JS, Yusuf S, Krauss RM. Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020 Aug 18;76(7):844-857. doi: 10.1016/j.jacc.2020.05.077. Epub 2020 Jun 17. PMID 32562735
• Lamarche B, et al. Dairy products and cardiovascular health: How strong is the evidence? J Am Coll Cardiol. 2016;67(12):1472-1489. doi:10.1016/j.jacc.2015.06.079. PMID: 27012404.
• Lordan R, Tsoupras A, Zabetakis I. Milk and dairy consumption: A review of cardiovascular health benefits and risks. Nutrients. 2018;10(8):993. doi:10.3390/nu10080993. PMID: 30087292.

Identifiers

NCT: NCT07176104 · SMASOEA-STEMI-FM01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗