Prospective Management of Plaque Instability With Statins and Extra Folic Acid

NCT07680595 | Recruiting Phase 1

• 1 other identifier: RX-2006-001
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Carotid Atherosclerotic Plaque

Outcome Measures

Primary Outcomes (1)

• Effects of oral folic acid combined with statins on carotid plaque thickness

  Change from baseline in carotid plaque thickness at 6 months post-treatment

  6 months

Secondary Outcomes (4)

• To investigate the effect of oral folic acid combined with statins on the maximum diameter of carotid plaques;

  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.

  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)

  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

  6 months

Study Arms (2)

Statin + Folic acid

EXPERIMENTAL

Drug: Atorvastatin plus folic acid

Statin

ACTIVE COMPARATOR

Drug: Atorvastatin

Interventions

Atorvastatin plus folic acid DRUG

Patients will receive oral folic acid 5 mg daily plus 20 mg atorvastatin regimen, with both treatments continuing for a duration of 6 months

Statin + Folic acid

Atorvastatin DRUG

Patients will receive 20 mg atorvastatin regimen for a duration of 6 months

Statin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Ruijin Hospital: lead

Study Sites (1)

Shanghai Jiao Tong University Medical School Affiliated Ruijing Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

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MeSH Terms

Interventions

Atorvastatin; Folic Acid

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Central Study Contacts

Junyi Yan, M.D.

CONTACT

+8613480161737; drsunyudong@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: July 2, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: July 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF

Locations

CN (1)