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

July 1, 2026 updated by: Ruijin Hospital

A Prospective, Exploratory, Cohort Clinical Study Comparing the Effects of Oral Statins With or Without Folic Acid on Carotid Plaque Stability.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

180

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200433
        • Recruiting
        • Shanghai Jiao Tong University Medical School Affiliated Ruijing Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Statin
Drug: Atorvastatin
Patients will receive 20 mg atorvastatin regimen for a duration of 6 months
Experimental: Statin + Folic acid
Drug: Atorvastatin plus folic acid
Patients will receive oral folic acid 5 mg daily plus 20 mg atorvastatin regimen, with both treatments continuing for a duration of 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of oral folic acid combined with statins on carotid plaque thickness
Time Frame: 6 months
Change from baseline in carotid plaque thickness at 6 months post-treatment
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To investigate the effect of oral folic acid combined with statins on the maximum diameter of carotid plaques;
Time Frame: 6 months
Changes in maximum plaque diameter
6 months
To investigate the changes in plaque composition ratios following the administration of oral folic acid combined with statins-including changes in intraplaque calcification area, fibrous cap thickness, intraplaque neovascularization, echo intensity.
Time Frame: 6 months
Plaque composition ratio: To observe post-treatment changes in intraplaque calcification area and fibrous cap thickness; to quantify intraplaque neovascularization density via contrast-enhanced ultrasound (CEUS); and to analyze changes in plaque echogenicity (grayscale values) in order to evaluate the stability of plaque components
6 months
To evaluate the impact on the proportions of peripheral blood B-cell subsets (via flow cytometry) and serum IgM/IgG titers (via ELISA)
Time Frame: 6 months
Determination of peripheral blood B-cell subset proportions (via flow cytometry) and serum IgM/IgG titers (via ELISA)
6 months
Safety and Tolerability: To monitor the incidence of adverse events (AEs) during the treatment period. This includes, but is not limited to, drug-specific safety profiles (e.g., gastrointestinal reactions, hepatic and renal dysfunction, and allergic reac
Time Frame: 6 months
Safety and tolerability: To record the incidence rate of adverse events (AEs) during the treatment period
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ruijin Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2026

Primary Completion (Estimated)

September 1, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

June 22, 2026

First Submitted That Met QC Criteria

July 1, 2026

First Posted (Actual)

July 2, 2026

Study Record Updates

Last Update Posted (Actual)

July 2, 2026

Last Update Submitted That Met QC Criteria

July 1, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RX-2006-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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