Rheumatoid ArthritisNCT04821050
Sacral Nerve Stimulation for Mild-to-Moderate or Refractory Rheumatoid Arthritis
A study testing Sacral nerve stimulation in people with Rheumatoid Arthritis, run by Nanjing First Hospital, Nanjing Medical University at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Sacral nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2021to Dec 2022
- Phase
- Interventional
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Dinglei Su
Nanjing, Jiangsu, 210006
Dinglei Su, +8613814011654, sudinglei@163.com
About this study
Official title: 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.
Read the 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:
- Disease activity-related indexes of RA: swelling joint number (SJC), tender joint number (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP);
- Serum levels of inflammatory cytokines, including IL-6, IL-17, TNF-α, etc;
- Patient report outcomes: Visual Analogue Scale (VAS) pain score, Health Assessment Questionnaire Disability Index (HAQ-DI) ;
- Indexes of autonomic nervous function: serum level of norepinephrine (NE), heart rate variability (HRV).
- Conditions
- Rheumatoid Arthritis
- Being tested
- Sacral nerve stimulation, Sham stimulation
- Keywords
- rheumatoid arthritis, Sacral nerve, Sacral nerve stimulation, Neuromodulation, randomized clinical trial, drug refractory
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sacral nerve stimulationDevice
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 stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Sacral nerve stimulation Receives: Device: Sacral nerve stimulation |
| Control | Sham comparator | Sham stimulation Receives: Device: Sham stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
The American College of Rheumatology (ACR) 20 response at Week 2 from Day 0
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.
Measured: Week 2
Secondary outcomes (4)
1. The Disease Activity Score 28-C-reactive protein (DAS28-CRP) good or moderate response as defined by European League Against Rheumatism (EULAR)
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
Measured: week 2
DAS28-CRP response (MCID -1.2) at Week 2
DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline
Measured: wee 2
3. Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22)
HAQ-DI response based on the MCID of -0.22 from baseline
Measured: week 2
Pain Visual Analogue Scale (scoring range 0 ~ 10)
Changes from baseline to week 2.
Measured: week 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2021
- Study start1 Mar 2021
- Primary completionOct 2022 (estimated)
- Study completionDec 2022 (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.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanjing First Hospital, Nanjing Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Minning Shen, associate professor, Principal investigator, Nanjing First Hospital, Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04821050
- Sponsor's protocol ID
- 202002053
- Status last verified
- Mar 2021
- First submitted
- 25 Mar 2021
- Last updated
- 4 Mar 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Wang X, Xu B, Wang G, Yang L, Su D, Chen JDZ. Sacral nerve stimulation modulates disease activity and autonomic function in active rheumatoid arthritis: a randomized pilot study. Clin Rheumatol. 2026 Jul 9. doi: 10.1007/s10067-026-08288-4. Online ahead of print.
PubMed 42423822
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Sham-Controlled, Double-Blind Study of Sacral Nerve Stimulation for Mild-to-Moderate or Refractory Rheumatoid Arthritis
- ClinicalTrials.gov ID
- NCT04821050
- Acronym / sponsor ID
- 202002053
- Conditions
- Rheumatoid Arthritis
- Keywords
- rheumatoid arthritis, Sacral nerve, Sacral nerve stimulation, Neuromodulation, randomized clinical trial, drug refractory
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Nanjing First Hospital, Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- Oct 2022 (estimated)
- Study completion
- Dec 2022 (estimated)
- First posted
- 29 Mar 2021 (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.
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.
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:
- Disease activity-related indexes of RA: swelling joint number (SJC), tender joint number (TJC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP);
- Serum levels of inflammatory cytokines, including IL-6, IL-17, TNF-α, etc;
- Patient report outcomes: Visual Analogue Scale (VAS) pain score, Health Assessment Questionnaire Disability Index (HAQ-DI) ;
- Indexes of autonomic nervous function: serum level of norepinephrine (NE), heart rate variability (HRV).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Device: Sacral nerve stimulationSacral nerve stimulation |
| Control | Sham comparator | Device: Sham stimulationSham stimulation |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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
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 |
|---|---|---|
| Sacral nerve stimulationA 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. | Device | Treatment |
| Sham stimulationShallow 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. | Device | Control |
Primary outcome
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.
4 secondary outcomes
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
DAS28-CRP response (MCID -1.2) at Week 2
Time frame: wee 2
3. Health Assessment Questionnaire Disability Index (HAQ-DI) response (MCID -0.22)
Time frame: week 2
Pain Visual Analogue Scale (scoring range 0 ~ 10)
Time frame: week 2
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2022.
- Derived from this study: PubMed 42423822Wang X, Xu B, Wang G, Yang L, Su D, Chen JDZ. Sacral nerve stimulation modulates disease activity and autonomic function in active rheumatoid arthritis: a randomized pilot study. Clin Rheumatol. 2026 Jul 9. doi: 10.1007/s10067-026-08288-4. Online ahead of print.
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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.
Minning Shen, associate professor principal investigator
Nanjing First Hospital, Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sacral nerve stimulation in people with Rheumatoid Arthritis, run by Nanjing First Hospital, Nanjing Medical University 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 3 inclusion and 7 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 4 Mar 2022. 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.
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 Dinglei Su, Dr. (+8613814011654, sudinglei@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The American College of Rheumatology (ACR) 20 response at Week 2 from Day 0 (time frame: Week 2). 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 NCT04821050, 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 4 Mar 2022.