Clinical trial NCT06054633: L-arginine for Knee Osteoarthritis Patients
Official title: Efficacy and Safety of Oral L-Arginine for Pain Relief in Knee Osteoarthritis: a Randomized, Double-Blind, Placebo-Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoarthritis, Knee
Keywords: osteoarthritis
L-arginine
Pain
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
Collaborators: name: Massachusetts General Hospital
name: School of Medicine, University of Nottingham
name: Memorial University of Newfoundland
First posted: 2023-09-26
Enrollment: 340
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score.
timeFrame: Baseline, Week 12
Secondary outcomes:
measure: Change From Baseline in WOMAC pain score.
timeFrame: Baseline, Weeks 2, 4 and 8
measure: Change From Baseline in Knee pain on a visual analogue scale (VAS).
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in WOMAC total score.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Change From Baseline in WOMAC stiffness score.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in WOMAC function score.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Patient global assessment of osteoarthritis (PGA-OA) score.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in SF-12 questionnaire score.
timeFrame: Baseline, Weeks 2, 4, 8 and 12
measure: Change From Baseline in Timed Up and Go Test (TUG).
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Chair-stand Test.
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Ultrasound-assessed knee synovitis.
timeFrame: Baseline, Week 12
measure: Rescue medicine consumption.
timeFrame: Weeks 2, 4, 8 and 12
measure: Change From Baseline in Level of C-reactive protein (CRP).
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Microbiota diversity and composition.
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Incidence of adverse events and serious adverse events.
timeFrame: Weeks 2, 4, 8 and 12
Other outcomes:
measure: Change From Baseline in Short Physical Performance Battery (SPPB) scores.
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Grip strength.
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Bone mineral density (BMD).
timeFrame: Baseline, Week 12
measure: Change From Baseline in DXA-based whole-body muscle mass.
timeFrame: Baseline, Week 12
measure: Change From Baseline in DXA-based whole body fat mass.
timeFrame: Baseline, Week 12
measure: Change From Baseline in pressure pain threshold (PPT).
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in mechanical temporal summation (mTS).
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in Hospital Anxiety and Depression Scale (HADS).
timeFrame: Baseline, Weeks 4, 8 and 12
measure: Change From Baseline in PainDETECT Questionnaire (PD-Q).
timeFrame: Baseline, Weeks 4, 8 and 12
Locations:
city: Changsha
country: China
facility: Xiangya Hospital
state: Hunan
Study officials:
affiliation: Xiangya Hospital of Central South University
name: Guanghua Lei, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: