L-arginine for Knee Osteoarthritis Patients

NCT ID: NCT06054633

Last Updated: 2025-06-02

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 340 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-03-20
• Study Completion Date: 2025-09-30

Brief Summary

This study will examine the pain-relief efficacy and safety of L-arginine in knee OA patients.

Detailed Description

Pain is the dominant symptom of knee osteoarthritis (KOA). The main management goal for people with KOA is to control pain without increasing treatment-related adverse effects (AEs). However, the commonly prescribed systemic analgesics have safety concerns, such as increased risk of cardiovascular and gastrointestinal AEs. Therefore, it is urgent to develop safe and effective treatment options.

L-arginine is one of the most commonly used oral nutritional supplements that has been widely used in patients with peripheral arterial disease, cystic fibrosis, and pregnant women with high risk of pre-eclampsia. The supplement has a high safety profile. Previous case-control and cross-sectional studies have found plasma L-arginine levels were lower in patients with knee OA than controls, suggesting that arginine deficiency may increase the risk of OA. The investigators previously observed an inverse dose-response relationship between levels of serum L-arginine and the risk of incident symptomatic KOA. Additionally, the investigators demonstrated that intra-articular injection of L-arginine solution relieved pain symptoms in a surgical rat model of OA. However, there is a paucity of high-quality clinical evidence on the effect of intake of L-arginine supplement on pain relief among patients with symptomatic KOA.

The investigators propose to conduct a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of oral L-arginine in patients with knee OA.

Conditions

Osteoarthritis, Knee

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Oral L-arginine

Participants in the intervention arm will receive oral L- arginine tablets, 2 g three times daily

Group Type: ACTIVE_COMPARATOR

L-arginine tablet

Intervention Type: DIETARY_SUPPLEMENT

L-arginine, 2 g, three times daily, for 12 weeks

Placebo

The control group will receive an identical inert placebo tablet, three times daily

Group Type: PLACEBO_COMPARATOR

Placebo tablet

Intervention Type: DIETARY_SUPPLEMENT

Identical inert placebo, three times daily, for 12 weeks

Interventions

L-arginine tablet

L-arginine, 2 g, three times daily, for 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

Placebo tablet

Identical inert placebo, three times daily, for 12 weeks

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

1. Age between 40 and 80 years.

2. Knee OA according to the American College of Rheumatology (ACR) clinical criteria.

3. Knee pain lasting 3 months or longer and a score of 7 or greater on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (standardized to range from 0-20).

4. Kellgren-Lawrence (KL) grade 2 or 3.

5. Willing to and able to provide written informed consent.

Exclusion Criteria

1. Any use of NSAIDs or other analgesics in the past two weeks.

2. History of injections of corticosteroids in the past three months or hyaluronic acid in the past 6 months in the index knee.

3. History of arthroscopy or open surgery in the index knee in the past 12 months.

4. History of a knee replacement in the index knee or planning to receive such a procedure within 3 months.

5. History of a severe injury in the index knee.

6. Pain in the index knee caused by inflammatory, autoimmune, neoplastic diseases or other diseases.

7. Abnormal liver or kidney functions, as defined by alanine transaminase or aspartate aminotransferase >two times the upper limit of normal, or blood urea nitrogen or serum creatinine >two times the upper limit of normal.

8. Severe respiratory diseases.

9. History of coronary artery disease and heart failure.

10. Uncontrolled hypertension or diabetes mellitus.

11. Diagnosis of malignant tumors.

12. Pregnant or contemplating pregnancy or breast-feeding.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

School of Medicine, University of Nottingham

UNKNOWN

Sponsor Role: collaborator

Memorial University of Newfoundland

OTHER

Sponsor Role: collaborator

Xiangya Hospital of Central South University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guanghua Lei, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Xiangya Hospital of Central South University

Locations

Xiangya Hospital

Changsha, Hunan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Yilun Wang, MD, PhD

Role: CONTACT

yilun_wang@csu.edu.cn

86-18692267896

Zhenglei Zhu, MD

Role: CONTACT

184890740@qq.com

86-13054173564

Facility Contacts

Guanghua Lei, Prof.

Role: primary

lei_guanghua@csu.edu.cn

86-13808429640

Other Identifiers

20230608

Identifier Type: -

Identifier Source: org_study_id