Sacral Nerve Stimulation for Mild-to-Moderate or Refractory Rheumatoid Arthritis

March 3, 2022 updated by: Nanjing First Hospital, Nanjing Medical University

A Randomized, Sham-Controlled, Double-Blind Study of Sacral Nerve Stimulation for Mild-to-Moderate or Refractory Rheumatoid Arthritis

This pilot study will assess the efficacy of sacral never stimulation (SNS) for the treatment of adult patients with active, mild-to-moderate rheumatoid arthritis or those with refractory disease. The study will enroll 60 subjects in a single center. All eligible subjects will be randomly divided into two groups at a ratio of 1:1. Half of the subjects will receive SNS (treatment) and the other half will receive sham stimulation (control). Subjects will be followed up for 2-4 weeks, according to their response to the treatment. Disease activity score, patient report outcomes and serum inflammatory cytokines will be observed before and after treatment.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Studies have shown that vagus nerve stimulation (VNS) may exert an anti-inflammatory effect through mechanisms like cholinergic anti-inflammatory pathway (CAP). This anti-inflammatory function of VNS has been verified in collagen induced arthritis (CIA) rats, RA patients, and animal models of inflammatory bowel disease (IBD). In recent years, it was reported that sacral nerve stimulation (SNS) is a safer way to exert a similar anti-inflammatory effect as VNS. Therefore, this study aims to explore the therapeutic effect of SNS on RA patients.

This is a randomized controlled clinical trial which will enroll 60 eligible RA patients. These subjects will be divided into two groups at a ratio of 1:1, the treatment group (Group 1) who will receive SNS and the control group (Group 2) who will receive sham stimulation. The patients will lie in prone position. In Group 1, a senior acupuncture doctor will pierce filiform needles through the sacral foramen into the S3 and S4 sacral nerves. These sites correspond to the Zhongliao and Xialiao acupoints in Traditional Chinese Medicine. In Group 2, shallow acupuncture stimulation will be performed at sites 8-10cm away from the acupoints in Group 1. In both groups, electrodes will be clamped on the filiform needles and an electrical current of 0.5 mA will be delivered. The stimulation will last for 60 minutes every time, once a day for 2 weeks. If the subjects respond to the treatment well, SNS treatment will be continued for 2 weeks. The following parameters will be measured before and 2-4 weeks after treatment:

  1. Disease activity-related indexes of RA: swelling joint number (SJC), tender joint number (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP);
  2. Serum levels of inflammatory cytokines, including IL-6, IL-17, TNF-α, etc;
  3. Patient report outcomes: Visual Analogue Scale (VAS) pain score, Health Assessment Questionnaire Disability Index (HAQ-DI) ;
  4. Indexes of autonomic nervous function: serum level of norepinephrine (NE), heart rate variability (HRV).

Study Type

Interventional

Enrollment (Anticipated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Jiangsu
      • Nanjing, Jiangsu, China, 210006
        • Recruiting
        • Dinglei Su
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 18-65 years of age at screening
  • Met the American College of Rheumatology criteria (2010) for RA
  • Active mild to moderate RA (defined as 3.2 < DAS28-CRP< 5.1) naïve to any medication; or refractory RA who demonstrated an inadequate response or loss of response to 2 or more conventional synthetic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs) after treatment for at least 6 months.

Exclusion Criteria:

  • Any severe chronic or uncontrolled comorbid disease, such as important organ failure, degree II and III heart block, clinically significant cardiovascular disease, severe infection, tumor, etc;
  • Combined with other connective tissue diseases
  • Cognitive impairment and can't cooperate
  • Pregnancy or breastfeeding
  • Bleeding or coagulation disorders
  • Localized skin infections
  • Intra-articular corticosteroid or pulse steroid within 2 weeks preceding the study

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Sacral nerve stimulation
Device: Sacral nerve stimulation

A senior acupuncture doctor will pierce filiform needles through the sacral foramen into the S3 and S4 sacral nerves. These sites correspond to the Zhongliao and Xialiao acupoints in Traditional Chinese Medicine.

Electrodes will be clamped on the filiform needles and an electrical current of 0.5 mA will be delivered. The stimulation will last for 60 minutes every time, once a day for 2 weeks.
Sham Comparator: Control
Sham stimulation
Device: Sham stimulation

Shallow acupuncture stimulation will be performed at sites 8-10cm away from the acupoints in Group 1.

Electrodes will be clamped on the filiform needles and an electrical current of 0.5 mA will be delivered. The stimulation will last for 60 minutes every time, once a day for 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The American College of Rheumatology (ACR) 20 response at Week 2 from Day 0
Time Frame: Week 2
Difference between treatment and control groups in the proportion of subjects who achieve at least 20% improvement from baseline to Week 2 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worse) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worse), subject pain (0=no pain to 10=worse), evaluator's global assessment (0=best to 10=worse), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL) with higher values representing worse outcome.
Week 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
1. The Disease Activity Score 28-C-reactive protein (DAS28-CRP) good or moderate response as defined by European League Against Rheumatism (EULAR)
Time Frame: week 2
The DAS28-CRP good or moderate response as defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worse), subject global assessment (0=best to 10=worse) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L) with higher values representing worse outcome
week 2
DAS28-CRP response (MCID -1.2) at Week 2
Time Frame: wee 2
DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline
wee 2
3. Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22)
Time Frame: week 2
HAQ-DI response based on the MCID of -0.22 from baseline
week 2
Pain Visual Analogue Scale (scoring range 0 ~ 10)
Time Frame: week 2
Changes from baseline to week 2.
week 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Nanjing First Hospital, Nanjing Medical University

Investigators

  • Principal Investigator: Minning Shen, associate professor, Nanjing First Hospital, Nanjing Medical University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2021

Primary Completion (Anticipated)

October 1, 2022

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

March 25, 2021

First Submitted That Met QC Criteria

March 25, 2021

First Posted (Actual)

March 29, 2021

Study Record Updates

Last Update Posted (Actual)

March 4, 2022

Last Update Submitted That Met QC Criteria

March 3, 2022

Last Verified

March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 202002053

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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