Role of L-Arginine Supplementation in the Treatment of Rheumatoid Arthritis

NCT04535427 | Unknown Phase 2

• 1 other identifier: L-ARG-RA
• Study Type: interventional
• Target: 144
• Locations: 1 country
• Sites: 1

Brief Summary

To investigate the role of L-arginine supplementation in the treatment of DMARDs-refractory moderate to severe rheumatoid arthritis

Conditions

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis; L-arginine

Outcome Measures

Primary Outcomes (1)

• The response rate of ACR20 after 24 weeks of L-arginine administration

  According to the American College of Rheumatology 20/50/70 criteria, the ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure \[most often Health Assessment Questionnaire (HAQ)\], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP).The reduction ratio of ACR20 after 24 weeks of high or low dose of L-arginine or placebo administration will be observed and documented as the measurement of primary outcome.

  Week 0+3+6+9+12+15+18+21+24+26

Secondary Outcomes (3)

• The response rate of ACR50/70 after 24 weeks of L-arginine administration

  Week 0+3+6+9+12+15+18+21+24+26

• The change of DAS28/ESR

  Week 0+3+6+9+12+15+18+21+24+26

• Numbers of participants with treatment-related adverse events

  Week 0+3+6+9+12+15+18+21+24+26

Study Arms (3)

Control

PLACEBO COMPARATOR

Participants in this arm will receive placebo per day.

Drug: Placebo

Low dose L-arginine

EXPERIMENTAL

Participants in this arm will receive 9g (3g tid) L-arginine per day.

Drug: L-arginine

High dose L-arginine

EXPERIMENTAL

Participants in this arm will receive 15g (5g tid) L-arginine per day.

Drug: L-arginine

Interventions

L-arginine DRUG

Low (3g every time, 3 times a day)or high dose (5g every time, 3 times a day) of L-arginine will be administered to the experimental groups for at least 24 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

High dose L-arginine; Low dose L-arginine

Placebo DRUG

Placebo will be administered to the control group for at least 24 weeks as an add-on treatment to the current DMARDs treatments for rheumatoid arthritis.

Control

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Chinese RA patients who are between 18 and 45 years old (inclusive) when signing the consent form, with a body mass index between 19 and 29 kg/m2 (inclusive), and weigh between 60 and 90 kg.
• The subject must be diagnosed with RA, and the judgment standard meets the 2010 American College of Rheumatology (ACR)/European Alliance Against Rheumatism (EULAR) RA classification standard;
• Active RA is defined as having ≥ 6 swollen joints and ≥ 6 tender joints at screening and baseline (based on 66/68 joints, excluding distal interphalangeal joints), and at least one of the following conditions occurs during screening: ESR ≥ 28 mm/hr, or serum CRP\> 10 mg/L;
• Positive rheumatoid factor or anti-cyclic citrulline peptide (CCP) during screening;
• Before using the study drug, the subject must have used MTX continuously for ≥ 12 weeks and have been stable for at least 8 weeks.
• mg/week dose and willing to use a stable dose throughout the study;
• Patients with moderate to severe disease activity after the current treatment of DMARDs, DAS28-ESR/CRP\>3.2;
• Subjects taking oral corticosteroids (≤ 10 mg of prednisone or equivalent) should use a stable dose for ≥ 4 weeks before screening;
• If subjects are taking non-steroidal anti-inflammatory drugs (NSAIDs) or low-efficiency analgesics, such as tramadol, neuronal cell compounds, they must use a stable dose for ≥ 2 weeks before screening.
• Considered as eligible subjects based on the following tuberculosis screening criteria:
• The subject has no history of latent or active tuberculosis before screening,
• No signs or symptoms of active tuberculosis in the history and/or physical examination,
• Have not had close contact with patients with active tuberculosis recently,
• One chest radiograph (including anteroposterior and lateral views) taken within three months before the administration of the study drug, and qualified radiologists have confirmed that there are no active tuberculosis foci or old inactivated tuberculosis foci.
• Non-smokers, or agree to smoke no more than 10 cigarettes or no more than 2 cigars per day during the entire study period. Note: According to the rules and regulations of the research center, smoking may be prohibited during hospitalization;

You may not qualify if:

• Subjects who meet any of the following criteria should not be selected for this study:
• RA patients combined with hypotension.
• RA patients combined with renal tubular acidosis and electrolyte imbalance.
• RA patients with significant gastrointestinal symptoms.
• According to the judgment of the main investigator, the subject is in a latent physical or psycho-medical state and will not be able to complete the study.
• Have had major surgery or traumatic surgery within 12 weeks before screening.
• Have received an organ transplant (except for corneal transplantation for more than three months before administration).
• Donated blood within 56 days before screening (the blood donation volume is not less than 500 mL).
• Currently suffering from malignant tumors or a history of malignant tumors.
• A history of known lymphoproliferative diseases, including lymphoma or possible signs and symptoms of lymphoproliferative diseases, such as lymphadenopathy and/or splenomegaly.
• Have a recent history of alcohol or drug abuse (within the previous 6 months).
• Positive urine toxicology screening for drugs of abuse include: cocaine, cannabidiol, phencyclidine, amphetamine, methamphetamine, benzodiazepines, barbiturates, opioids, and C Oxyphene, methaqualone, methadone and tricyclic antidepressants.
• When admitted to the research center before the study drug was administered, the urine alcohol screening or breath alcohol test results were positive.
• Have a history of latent or active granulomatous infection before screening, including histoplasmosis or coccidioidomycosis.
• Have a history of known or suspected intolerance or hypersensitivity to any biological drug treatment.

Sponsors & Collaborators

• RenJi Hospital: lead

Study Sites (1)

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine

Shanghai, China

Location

Related Publications (1)

• Hannemann N, Cao S, Eriksson D, Schnelzer A, Jordan J, Eberhardt M, Schleicher U, Rech J, Ramming A, Uebe S, Ekici A, Canete JD, Chen X, Bauerle T, Vera J, Bogdan C, Schett G, Bozec A. Transcription factor Fra-1 targets arginase-1 to enhance macrophage-mediated inflammation in arthritis. J Clin Invest. 2019 Apr 16;129(7):2669-2684. doi: 10.1172/JCI96832.

  PMID: 30990796 BACKGROUND

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Arginine

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Study Officials

• Xiaoxiang Chen, PhD

  Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiaoxiang Chen, PhD

CONTACT

0086 13801974325; xiaoxiang0721@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2020
• First Posted: September 2, 2020
• Study Start: January 1, 2021
• Primary Completion: January 1, 2023
• Study Completion: December 31, 2023
• Last Updated: September 2, 2020

Record last verified: 2020-08

Locations

CN (1)