Prospective Management of Plaque Instability With Statins and Extra Folic Acid (PROMISE)

Shanghai Jiao Tong University

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Carotid Atherosclerotic Plaque

Treatments

Drug: Atorvastatin plus folic acid

Drug: Atorvastatin

Study type

Interventional

Funder types

Other

Identifiers

NCT07680595

RX-2006-001

Details and patient eligibility

About

This is a prospective, exploratory, cohort clinical study aiming to further investigate the direct impact of folic acid on the stability of carotid atherosclerotic plaques, building upon substantial clinical evidence confirming that folic acid supplementation reduces the risk of stroke in hypertensive patients, thereby providing a basis for subsequent confirmatory randomized controlled trials. The study will enroll patients with carotid plaques who have not undergone carotid endarterectomy or stent implantation, with lesions defined-according to the Expert Consensus on Standardized Ultrasound Operation and Reporting of Carotid Atherosclerotic Plaques (2025, Shanghai)-as the presence of at least one site with a carotid intima-media thickness (cIMT) ≥ 1.5 mm or visible plaque formation. Participants will be allocated into Cohort 1 (statin therapy) and Cohort 2 (statin therapy plus folic acid); Cohort 1 will receive oral atorvastatin 20 mg daily, while Cohort 2 will receive an additional oral folic acid 5 mg daily on top of the 20 mg oral atorvastatin regimen, both for a continuous duration of 6 months. Statin therapy in both groups will be standardized and managed in accordance with current clinical guidelines, and all subjects will undergo comprehensive evaluations at baseline and after the 6-month intervention. The primary endpoint is the change in carotid plaque thickness at 6 months post-treatment, while secondary endpoints encompass changes in maximum plaque diameter, analysis of plaque composition ratio, and the regulatory effects on serum metabolic markers and the peripheral immune microenvironment, alongside continuous monitoring of treatment-related adverse events throughout the study to comprehensively evaluate overall safety and tolerability.

Enrollment

180 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Signed and dated written informed consent form (version approved by the Ethics Committee);
Voluntary participation and commitment to comply with the study protocol;
Aged 18 to 75 years, regardless of sex;
Confirmed carotid plaque by ultrasound or computed tomography angiography (CTA), defined-according to the Expert Consensus on Standardized Ultrasound Operation and Reporting of Carotid Atherosclerotic Plaques (2025, Shanghai)-as the presence of at least one lesion with a carotid intima-media thickness (cIMT) ≥ 1.5 mm or plaque formation;
Able to cooperate and complete the 6-month study follow-up, including regular imaging examinations and blood sample collections.

Exclusion criteria

History of plaque excision or interventional procedures, such as carotid endarterectomy (CEA) or carotid artery stenting (CAS);
History of severe hepatic or renal impairment, malignancies, autoimmune diseases, or psychiatric disorders;
Pregnant or lactating women;
Hypersensitivity (or allergy) to any components of the study medications;
Current or long-term regular use of any dietary supplements or medications that may significantly affect the folate metabolic cycle (e.g., vitamin B6, vitamin B12, multivitamins, etc.).