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

Raffaele Marfella

Status: Begins enrollment this month

Conditions: ST-elevation Myocardial Infarction (STEMI); In-stent Restenosis

Treatments: Dietary Supplement: Non-Functional Bovine Milk; Dietary Supplement: Functional Bovine Milk

Study type: Interventional

Funder types: Other

Identifiers

NCT07176104

SMASOEA-STEMI-FM01

Details and patient eligibility

About

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.

Full 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.

Enrollment: 140 estimated patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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140 participants in 2 patient groups

Functional Milk Group

Experimental group

Description:

Participants will receive daily supplementation with functionalized bovine milk enriched with bioactive peptides and optimised lipid profile, in addition to guideline-directed secondary prevention therapy, for 12 months.

Treatment:

Dietary Supplement: Functional Bovine Milk

Non-Functional Milk Group

Experimental group

Description:

Participants will receive daily supplementation with an isocaloric non-functional bovine milk matched in appearance, taste, and packaging to the functionalized milk, in addition to guideline-directed secondary prevention therapy, for 12 months.

Treatment:

Dietary Supplement: Non-Functional Bovine Milk