Clinical Trial of Electroacupuncture in Axial Spondyloarthritis (E-AcuSpA) (E-AcuSpA)

A Randomized Controlled Trial of Electroacupuncture in the Management of Patients With Axial Spondyloarthritis in Singapore (E-AcuSpA)

Axial spondyloarthritis (AxSpA) is a chronic disease that causes severe disability and poor quality of life. Current treatment options are limited and there are still significant non-responders to current western medications. Manual acupuncture has been shown to reduce pain in patients with AxSpA. There have been reports of electroacupuncture demonstrating more sustained pain relief. Therefore, the investigators aim to determine the clinical effectiveness, safety and cost-effectiveness of electroacupuncture as compared to manual acupuncture for patients with AxSpA through a randomized controlled trial.

Study Overview

• Status: Recruiting
• Conditions: Spondylarthritis; Axial Spondyloarthritis
• Intervention / Treatment: Other: Electroacupuncture; Other: Manual acupuncture

Detailed Description

Patients with active axial spondyloarthritis despite non-steroidal anti-inflammatory drugs (NSAIDs) or biologics, will be randomly allocated to receive electroacupuncture or manual acupuncture on a 1:1 basis via random permuted block randomization. All patients will receive their standard of care (drug therapy and physiotherapy) as background therapy. This study will not be investigating any therapeutic or medicinal products (drugs).

Primary outcome would be the mean difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score between the 2 groups over 12 weeks (as assessed at weeks 0, 3, 6, 9, 12) adjusted for baseline covariate and other potential confounders. Patients will be followed up for BASDAI, other clinical, quality of life (QoL), economic outcomes as well as Traditional Chinese Medicine (TCM) syndrome scores over time for secondary and exploratory outcomes. A cost-effectiveness analysis will be performed. Adverse events will be recorded.

The primary hypothesis is that electroacupuncture may result in better disease activity control in patients with AxSpA as compared to manual acupuncture over 12 weeks, while secondary hypothesis is that electroacupuncture may result in greater improvements in other clinical and quality of life outcomes as compared to those receiving manual acupuncture over 24 weeks. The investigators also hypothesize that there is no difference in safety between both arms.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Warren Fong; Phone Number: +65 63214028; Email: warren.fong.w.s@singhealth.com.sg

Study Locations

• Singapore
  • Singapore, Singapore, 169608
    • Recruiting
    • Singapore General Hospital
    • Contact: Lay Lian Tan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Aged 21 years of age or older
• Diagnosed with AxSpA according to the 2009 Assessment of Spondyloarthritis International Society (ASAS) criteria
• Bath AS Disease Activity Index (BASDAI) score ≥4 on a 11-point Numerical Rating Scale (NRS)
• Failed 2 sequential NSAIDs (including cyclooxygenase-2 inhibitor) at maximal tolerated doses for ≥4 weeks in total
• Patients on concomitant biological therapy (e.g. tumour necrosis factor inhibitor therapy, anti-interleukin 17) or non-biologic disease-modifying antirheumatic drugs (DMARDs) (e.g. methotrexate (MTX) or sulfasalazine (SSZ) or leflunomide (LEF)) at study entry must be on the drug for ≥12 weeks and at stable dose for ≥4 weeks prior to randomisation
• Patients taking systemic corticosteroids have to be on stable dose of ≤10mg/day prednisolone or equivalent for at least two weeks before randomisation.

Exclusion Criteria:

• Pregnant or breastfeeding women
• With bleeding disorders
• With blood-borne communicable diseases (e.g. hepatitis B, hepatitis C, human immunodeficiency virus, etc)
• With implantable electrical device (e.g. pacemaker)
• Suffering from impaired skin sensation or serious skin lesions along the vertebrae

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Electroacupuncture; In addition to usual rheumatological care, patients in the electroacupuncture arm will undergo 2 courses of electroacupuncture treatment. Each treatment course will consist of 10 acupuncture sessions held over 5 weeks. Patient will take a break of 5-7 days in between each course of acupuncture.	Other: Electroacupuncture; Manual acupuncture (see procedures below) will be administered first to obtain the "de qi" sensation. After "de qi" is obtained, the electroacupuncture unit will be connected to 1-3 pairs of acupoints. Current intensity used will be based on the tolerance of each patient. Needles with electrical stimulation will be retained for 30 min. Main acupoints will be Jingjin points (meridian sinews) along the Bladder meridian of Foot - Taiyang, such as Shenshuci, as well as Jingjin points (meridian sinews) at transverse process from L2 to L4, iliac crest and spinous process from S1 to S4. Secondary acupoints will also be selected based on patients' syndromes and symptoms.
Active Comparator: Manual acupuncture; In addition to usual rheumatological care, patients in the manual acupuncture arm will undergo 2 courses of manual acupuncture treatment. Each treatment course will consist of 10 acupuncture sessions held over 5 weeks. Patient will take a break of 5-7 days in between each course of acupuncture.	Other: Manual acupuncture; After disinfecting the acupuncture points, acupuncture will be performed with the patient lying prone. Depending on the acupuncture points, 0.25mm X 25-75 mm sterile acupuncture needle will be used. Needles will be inserted 10-50 mm and either rotating manipulation or lifting-thrusting manipulation will be used to achieve "de qi" (a compositional sensation including soreness, numbness, distention and heaviness). Acupoints used will be similar to those mentioned for electroacupuncture (see above).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score between both groups	Mean difference in BASDAI score between both groups from baseline to weeks 3, 6, 9 and 12. BASDAI score ranges from 0-10, with higher scores indicating higher disease activity.	Week 3, 6, 9, 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in Bath Ankylosing Spondylitis Functional Index (BASFI) score between both groups	Mean difference in BASFI score between both groups from baseline to weeks 6, 12 and 24. BASFI score ranges from 0-10, with higher scores indicating poorer functioning.	Week 6, 12, 24
Mean difference in Bath Ankylosing Spondylitis Patient Global score (BAS-G) between both groups	Mean difference in BAS-G score between both groups from baseline to weeks 6, 12 and 24. BAS-G score ranges from 0-10, with higher scores reflecting poorer well-being.	Week 6, 12, 24
Mean difference in Assessment of Spondyloarthritis International Society Health Index (ASAS HI) score between both groups	Mean difference in ASAS HI score between both groups from baseline to weeks 6, 12 and 24. ASAS HI score ranges from 0-17, with higher scores indicating poorer health status.	Week 6, 12, 24
Mean difference in Ankylosing Spondylitis Quality of Life (ASQoL) score between both groups	Mean difference in ASQoL score between both groups from baseline to weeks 6, 12 and 24. ASQoL score ranges from 0-18, with higher scores indicating worse quality of life.	Week 6, 12, 24
Mean difference in EuroQol- 5 Dimension (EQ-5D) score between both groups	Mean difference in EQ-5D score between both groups from baseline to weeks 6, 12 and 24. EQ-5D consists of a descriptive system and a visual analogue scale. The descriptive system covers 5 dimensions: mobility, self-care, usual activities, pain/ discomfort and anxiety/ depression. Each dimension has a minimum and maximum score of 1 and 5 respectively, with higher scores representing a greater problem in that dimension. The visual analogue scale ranges from 0-100, with lower scores indicating poorer health status.	Week 6, 12, 24
Mean difference in Work Productivity and Activity Impairment (WPAI) score between both groups	Mean difference in WPAI score between both groups from baseline to weeks 6, 12 and 24. WPAI measures absenteeism, presenteeism, work productivity loss and activity impairment. These are expressed as percentages, from 0-100, with higher numbers indicating greater impairment and less productivity.	Week 6, 12, 24
Mean difference in healthcare costs between both groups	Mean difference in healthcare costs will be assessed for both groups at weeks 6, 12 and 24.	Week 6, 12, 24
Mean difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score between both groups	Mean difference in BASDAI score between both groups from baseline to week 24. BASDAI score ranges from 0-10, with higher scores indicating higher disease activity.	Week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean difference in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score between both groups	Mean difference in BASDAI score between both groups from baseline to week 52. BASDAI score ranges from 0-10, with higher scores indicating higher disease activity.	Week 52
Mean difference in Bath Ankylosing Spondylitis Functional Index (BASFI) score between both groups	Mean difference in BASFI score between both groups from baseline to week 52. BASFI score ranges from 0-10, with higher scores indicating poorer functioning.	Week 52
Mean difference in Bath Ankylosing Spondylitis Patient Global score (BAS-G) between both groups	Mean difference in BAS-G score between both groups from baseline to week 52. BAS-G score ranges from 0-10, with higher scores reflecting poorer well-being.	Week 52
Mean difference in Assessment of Spondyloarthritis International Society Health Index (ASAS HI) score between both groups	Mean difference in ASAS HI score between both groups from baseline to week 52. ASAS HI score ranges from 0-17, with higher scores indicating poorer health status.	Week 52
Mean difference in Ankylosing Spondylitis Quality of Life (ASQoL) score between both groups	Mean difference in ASQoL score between both groups from baseline to week 52. ASQoL score ranges from 0-18, with higher scores indicating worse quality of life.	Week 52
Mean difference in EuroQol- 5 Dimension (EQ-5D) score between both groups	Mean difference in EQ-5D score between both groups from baseline to week 52. EQ-5D consists of a descriptive system and a visual analogue scale. The descriptive system covers 5 dimensions: mobility, self-care, usual activities, pain/ discomfort and anxiety/ depression. Each dimension has a minimum and maximum score of 1 and 5 respectively, with higher scores representing a greater problem for that dimension. The visual analogue scale ranges from 0-100, with lower scores indicating poorer health status.	Week 52
Mean difference in Work Productivity and Activity Impairment (WPAI) score between both groups	Mean difference in WPAI score between both groups from baseline to week 52. WPAI measures absenteeism, presenteeism, work productivity loss and activity impairment. These are expressed as percentages, from 0-100, with higher numbers indicating greater impairment and less productivity.	Week 52
Mean difference in healthcare costs will be assessed for both groups	Mean difference in healthcare costs will be assessed for both groups at week 52.	Week 52
Mean difference in Traditional Chinese Medicine (TCM) syndrome scores will be assessed for both groups	Mean difference in TCM syndrome scores will be assessed for both groups at weeks 0, 3, 6, 9, and 12. In this study, the main TCM syndromes are: 1) Yang" deficiency in kidneys and "Du" meridian, 2) Deficiency in liver and kidney, 3) Blockage due to stagnated blood, 4) Blockage due to damp heat syndrome, and 5) Blockage due to damp cold syndrome. Each symptom under the syndromes has a minimum score of 0 and maximum score of 3, with higher scores indicating greater symptom severity. Scores would be added up to tabulate syndrome scores, with higher scores indicating greater syndrome severity.	Week 3, 6, 9, 12

Collaborators and Investigators

• Sponsor: Singapore General Hospital
• Collaborators: Duke-NUS Graduate Medical School; National University of Singapore; Thong Chai Institute of Medical Research
• Investigators: Principal Investigator: Warren Fong, Singapore General Hospital

Publications and helpful links

General Publications

• Kwan YH, Fong W, Ang XL, Tan CS, Tai BC, Huang Y, Bilger M, Phang JK, Tan HC, Lee JV, Sun L, Tan CT, Dong BQ, Koh HL, Leung YY, Lui NL, Yeo SI, Ng SC, Fong KY, Thumboo J, Ostbye T. Traditional Chinese medicine (TCM) collaborative care for patients with axial spondyloarthritis (AcuSpA): protocol for a pragmatic randomized controlled trial. Trials. 2019 Jan 14;20(1):46. doi: 10.1186/s13063-018-3117-2.

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2021
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 20, 2020

Study Record Updates

• Last Update Posted (Actual): December 26, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Acupuncture; Electroacupuncture; Manual acupuncture
• Additional Relevant MeSH Terms: Infections; Joint Diseases; Musculoskeletal Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthropathies; Bone Diseases, Infectious; Ankylosis; Spondylitis; Spondylarthritis; Axial Spondyloarthritis
• Other Study ID Numbers: 2019/2435

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No