Rheumatoid ArthritisPhase 2NCT04535427
Role of L-Arginine Supplementation in the Treatment of Rheumatoid Arthritis
A Phase 2 study testing L-arginine in people with Rheumatoid Arthritis, run by RenJi Hospital at 1 site in China.
Trial summary
To investigate the role of L-arginine supplementation in the treatment of DMARDs-refractory moderate to severe rheumatoid arthritis Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- L-arginine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2021to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- In order to be eligible for inclusion in this study, subjects must meet all of the following criteria:
- 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.
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- 10-15mg/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;
- Agree to abstain from alcohol within 48 hours before the administration of the study drug and during the study hospitalization, and agree to drink no more than 10g of alcohol per day during the rest of the study;
- Agree to limit caffeine intake, with a daily limit of five cups of tea, or three cups of coffee or six cans of cola. Do not take caffeine within 4 hours before receiving the electrocardiogram;
- Agree to fully use birth control measures to prevent pregnancy (such as birth control pills, uterine contraceptive devices, or protective measures using spermicides) for at least six months after receiving study drug treatment;
- Except for taking acetaminophen and previously taken multivitamins at the recommended dose, as well as the drugs approved by the investigator and medical monitor, the subject agreed to not use prescription drugs for 14 days before receiving the study drug treatment until the end of the study , Over-the-counter medicines, herbal medicines, proprietary Chinese medicines or "natural" medicines;
- Demonstrate a clear understanding of the research and sign an informed consent (ICF);
- Personal willingness and ability to comply with the study follow-up schedule and other requirements of the study protocol.
Who cannot join
- 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.
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- 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.
- Chest x-ray pictures taken within 3 months before the first administration of the study drug showed abnormalities suggesting malignant tumors or current active infections (including TB).
- Have nontuberculous mycobacteria or opportunistic infections (such as cytomegalovirus, pneumocystis disease, aspergillosis) within 6 months before screening.
- Have or have had a serious infection (such as sepsis, pneumonia, or pyelonephritis) or were hospitalized for infection or received fourth-generation antibiotic treatment within 2 months before screening.
- A history of chronic or recurrent infectious diseases, including but not limited to the following diseases: chronic kidney infection, chronic chest infection (for example, bronchiectasis), recurrent urinary tract infection (recurrent pyelonephritis or chronic non-dilated bladder) Inflammation), or open, draining or infectious skin wounds or ulcers.
- Serum was positive for HIV-1 or HIV-2, hepatitis B virus (HBV) or hepatitis C virus (HCV) during screening.
- Syphilis (Treponema pallidum) test (qualitative test) was positive at screening.
- The staff of the main researcher or research center and directly participate in the research or other research of the main researcher or research center, including the staff or the family members of the main researcher.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai
Xiaoxiang Chen, Doctor, 0086 13801974325, xiaoxiang0721@126.com
About this study
To investigate the role of L-arginine supplementation in the treatment of DMARDs-refractory moderate to severe rheumatoid arthritis
- Conditions
- Rheumatoid Arthritis
- Being tested
- L-arginine, Placebo
- Keywords
- Rheumatoid Arthritis, L-arginine
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | Participants in this arm will receive placebo per day. Receives: Drug: Placebo |
| Low dose L-arginine | Experimental | Participants in this arm will receive 9g (3g tid) L-arginine per day. Receives: Drug: L-arginine |
| High dose L-arginine | Experimental | Participants in this arm will receive 15g (5g tid) L-arginine per day. Receives: Drug: L-arginine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
According to the American College of Rheumatology 20/50/70 criteria, ACR50/70 are the same instruments with improvement levels defined as 50% and 70% respectively versus 20% for ACR20. The reduction ratio of ACR 50/70 after 24 weeks of high or low dose of L-arginine or placebo administration will be observed and documented as the measurement of secondary outcome.
Measured: Week 0+3+6+9+12+15+18+21+24+26
The change of DAS28/ESR
The DAS28 Scores indicate how active a patient's rheumatoid arthritis is currently, and can be trended over time. DAS stands for 'disease activity score' and the number 28 refers to the 28 joints that are examined in this assessment. The EULAR Response Criteria also allows clinicians to use DAS28 to categorize the effectiveness of a particular therapy.The formula for DAS28/ESR is (0.56*√(Tender Joint Count)+0.28*√(Swollen Joint Count)+0.7*ln(ESR)+0.014*(global health)). In this study, the change of DAS28/ESR will also be observed and documented as the measurement of secondary outcome.
Measured: Week 0+3+6+9+12+15+18+21+24+26
Numbers of participants with treatment-related adverse events
The adverse events in each group will be observed and documented during the whole procedure to show the safety of L-arginine treatment.
Measured: Week 0+3+6+9+12+15+18+21+24+26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2020
- Study start1 Jan 2021 (estimated)
- Primary completion1 Jan 2023 (estimated)
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by RenJi HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- RenJi Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Xiaoxiang Chen, PhD, Principal investigator, Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04535427
- Sponsor's protocol ID
- L-ARG-RA
- Status last verified
- Aug 2020
- First submitted
- 22 Aug 2020
- Last updated
- 2 Sep 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 30990796
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of L-Arginine Supplementation in the Treatment of Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT04535427
- Acronym / sponsor ID
- L-ARG-RA
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis, L-arginine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- RenJi HospitalUniversity, hospital or other
- Study start
- 1 Jan 2021 (estimated)
- Primary completion
- 1 Jan 2023 (estimated)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 2 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To investigate the role of L-arginine supplementation in the treatment of DMARDs-refractory moderate to severe rheumatoid arthritis
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | Drug: PlaceboParticipants in this arm will receive placebo per day. |
| Low dose L-arginine | Experimental | Drug: L-arginineParticipants in this arm will receive 9g (3g tid) L-arginine per day. |
| High dose L-arginine | Experimental | Drug: L-arginineParticipants in this arm will receive 15g (5g tid) L-arginine per day. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (22 listed)
- In order to be eligible for inclusion in this study, subjects must meet all of the following criteria:
- 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;
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-arginineLow (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. | Drug | High dose L-arginine, Low dose L-arginine |
| PlaceboPlacebo 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. | Drug | Control |
Primary outcome
The response rate of ACR20 after 24 weeks of L-arginine administration
Time frame: Week 0+3+6+9+12+15+18+21+24+26
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.
3 secondary outcomes
The response rate of ACR50/70 after 24 weeks of L-arginine administration
Time frame: Week 0+3+6+9+12+15+18+21+24+26
The change of DAS28/ESR
Time frame: Week 0+3+6+9+12+15+18+21+24+26
Numbers of participants with treatment-related adverse events
Time frame: Week 0+3+6+9+12+15+18+21+24+26
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2020.
- Background: PubMed 30990796Hannemann 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiaoxiang Chen, PhD principal investigator
Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-arginine in people with Rheumatoid Arthritis, run by RenJi Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 2 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Xiaoxiang Chen, PhD (0086 13801974325, xiaoxiang0721@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The response rate of ACR20 after 24 weeks of L-arginine administration (time frame: Week 0+3+6+9+12+15+18+21+24+26). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04535427, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2020.