Acupuncture Study on Rheumatoid Arthritis, Monitoring Microbiome and Blood

Non Inferiority Trial for the Study of Acupuncture on Rheumatoid Arthritis

Acupuncture is used and recommended by the WHO for the treatment of Rheumatoid Arthritis.

The molecular bases of this recommendation are not known, the investigators want to compare with the usage of high-throughput molecular technologies the variations occurring in patients treated with acupuncture and conventional treatment with the ones treated with conventional treatment only. The investigators observe the variations in blood and in the gut microbiome.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: methotrexate; Drug: non-steroidal anti-inflammatory drug (NSAID); Drug: leflunomide; Procedure: Acupuncture

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200052
      • Shanghai GuangHua Hospital of integrated traditional and western medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The patient should be diagnosed as the first or second stage of rheumatoid Arthritis (RA) and checked with X ray for additional diagnose.
• diagnosed for RA according to ACR(1987)

• the patient should be in the active stage of the disease, defined as：

  1. swollen joints >3
  2. tender joints > 5
  3. any one of the following： (c1.) morning stiffness lasting more than 45 minutes (c2.) Erythrocyte Sedimentation Rate (ESR) >= 28mm/h (c3.) C-reactive protein (CRP)>= 12mg/L
• Should not be resistant to MTX nor leflunomide

• Blood test should satisfy:

  1. Hemoglobin (Hb)>=85g/L
  2. White cell >=3.5 10+9/L
  3. Platelets >= 100 10+9/L
  4. Liver function: serum alanine aminotransaminase (ALT), aspartate transaminase (AST) and total bilirubin (TBil) should be less than 1.5 times the upper limit of normal (ULN)
  5. Kidney function: Serum creatinine (Cr) level should be less than ULN.
  6. Pregnancy test should be negative
• should be positive for anti-cyclic citrullinated protein antibodies (anti-CCP).
• should agree to sign the informed consent

Exclusion Criteria:

• Serious diseases affecting liver, kidney, heart and lung, or diseases related to hematologic，endocrine and nervous systems. .
• Be treated by MTX or Leflunomide in the last 3 months.
• Be treated with cortical hormone （could be intramuscular injection, intravenous injection or injection to articular cavity） in the last 4 weeks.
• Be treated with biological agents, such as antagonist of TNF-alpha,IL-6, and CD20 mono antibody in the last 3 months.
• Be treated by chronic medicine, such as immunosuppressive agent, Penicillamine, chloroquine and gold based Disease-modifying antirheumatic drugs (DMARDs) in the last 3 months.
• Pregnant and breast-feeding woman
• Having history of serious drug allergy
• In the acute or chronic phase of infection (such as lung diseases)
• Easy bleeding patients or patients with local skin infection (only for acupuncture)
• The patients cannot accept acupuncture (only for acupuncture)
• Be treated with acupuncture in the past 3 months（only for acupuncture）.
• No pregnant and breast-feeding woman.
• No history of serious drug allergy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acupuncture; Acupuncture plus conventional treatment (methotrexate+leflunomide+non-steroid anti-inflammatory drugs)	Drug: methotrexate; methotrexate: 7.5mg/week to 15mg/week for 3 months; Drug: non-steroidal anti-inflammatory drug (NSAID); NSAID: 100mg twice a day for 3 months; Drug: leflunomide; leflunomide: 20mg/day for 3 months; Procedure: Acupuncture; 30 minutes acupuncture every other day for 3 months. Basic acupoints: Zusanli, st36; Taixi，KI3）; Shenxu, BL23 Additional acupoints due to personal condition: Waiguan，SJ5; Baxie，Ex-UE9;Yinlingquan，(SP9）; Quchi，LI11; Yanglingquan，GB34; Xuehai，SP10; Dazhu，BL11; Dazhui，DU14; Pixu，BL20.
Active Comparator: Control; Conventional treatment (methotrexate+leflunomide+non-steroid anti-inflammatory drugs)	Drug: methotrexate; methotrexate: 7.5mg/week to 15mg/week for 3 months; Drug: non-steroidal anti-inflammatory drug (NSAID); NSAID: 100mg twice a day for 3 months; Drug: leflunomide; leflunomide: 20mg/day for 3 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR20 Response Rate at 3 Weeks	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to 3 weeks
ACR20 Response Rate at 3 Months	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to three months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ACR50 Response Rate at 3 Weeks	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to 3 weeks
ACR50 Response Rate at 3 Months	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to three months
ACR70 Response Rate at 3 Weeks	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to 3 weeks
ACR70 Response Rate at 3 Months	ACR criteria stands for: American College of Rheumatology Criteria. ACR criteria measures improvement in tender or swollen joint counts and improvement in three of the following five parameters: acute phase reactant (such as sedimentation rate) patient assessment physician assessment pain scale disability/functional questionnaire The number indicates the percentage of improvement in tender or swollen joint counts as well percentage improvement in three of the other five criteria (patient's assessment of pain, a physician's global assessment of disease, a patient's global assessment of disease, physical function as assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the level of acute-phase reactant)	From baseline to three months
DAS28 at Baseline	The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count. The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 2.6-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease	At baseline
DAS28 at 3 Weeks	The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count. The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 0-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease	At 3 weeks
DAS28 at 3 Months	The DAS28 (disease activity score) considers 28 tender and swollen joint counts, general health (GH; patient assessment of disease activity using a 100 mm visual analogue scale (VAS) with 0 = best, 100 = worst), plus levels of an acute phase reactant (either the level of erythrocyte sedimentation rate ESR (mm/h) or C-reactive protein CRP (mg/litre)). DAS28 values were calculated as follows: DAS28 (CRP) = 0.56*√(TJC28) +0.28*√(SJC28)+0.014*GH+0.36*ln(CRP+1)+0.96; DAS28 (ESR) = 0.56*√(TJC28)+0.28*√(SJC28)+0.014*GH+0.70*ln(ESR), where TJC = tender joint count and SJC = swollen joint count. The scale does not have bounds. DAS28 total score < 2,6 means remission DAS28 total score ranged between 0-3.2 means inactive disease; DAS28 total score ranged between 3.3-5.1 means moderate disease activity; DAS28 total score >5.1 means very active disease	At 3 months

Collaborators and Investigators

• Sponsor: Chinese Academy of Sciences
• Collaborators: Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine
• Investigators: Study Chair: Christine Nardini, PhD, Key laboratory of Computational Biology,Chines Academy of Sciences-Max Planck Institute-CAS MPG PICB; Study Chair: Christine Nardini, PhD, Consiglio Nazionale delle Ricerche Istituto per le Applicazioni del Calcolo "Mauro Picone"; Principal Investigator: Yuanhua Liu, Shanghai Institute of Biochemistry and Cell Biology, CAS, Shanghai, PRC; Principal Investigator: Yongying Liang, Guanghua Hospital, Shanghai, PRC; Principal Investigator: Xiaoyuan Zhou, Group of Clinical Genomic Networks, Shanghai Institutes for Biological Sciences, CAS-MPG, China; Principal Investigator: Jennifer E. Dent, Group of Clinical Genomic Networks, Shanghai Institutes for Biological Sciences, CAS-MPG, China; Principal Investigator: Ting Jiang, Department of Neurology, University of California, San Francisco, USA; Principal Investigator: Ding Qin, Guanghua Hospital, Shanghai, PRC; Principal Investigator: Youtao Lu, Group of Clinical Genomic Networks, Shanghai Institutes for Biological Sciences, CAS-MPG, China; Study Director: Dongyi He, Guanghua Hospital, Shanghai, PRC

Publications and helpful links

Helpful Links

• Book chapter, planned release in November 2023

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): December 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: June 5, 2012
• First Submitted That Met QC Criteria: June 12, 2012
• First Posted (Estimated): June 14, 2012

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: blood; Rheumatoid Arthritis; gut intestinal microbiome
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Anti-Inflammatory Agents; Methotrexate; Leflunomide; Anti-Inflammatory Agents, Non-Steroidal
• Other Study ID Numbers: acumicro

Plan for Individual participant data (IPD)

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: GSE59526