Clinical trial NCT05374057: Chiropractic Spinal Manipulative Therapy for Acute Neck Pain
Official title: Chiropractic Spinal Manipulative Therapy for Acute Neck Pain: a 4- Arm Clinical Placebo Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Acute Neck Pain
Keywords: Randomized controlled trial (RCT)
Clinical trial
Acute neck pain
Lead sponsor: University Hospital, Akershus
Sponsor class: OTHER
Collaborators: name: University of Oslo
name: The Dam Foundation
First posted: 2022-05-13
Enrollment: 320
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A 4-arm parallel clinical placebo randomized controlled Trial.
Primary purpose: TREATMENT

Brief summary: Acute neck is very common in the general population and often causes disability over shorter or longer time periods. Unfortunately, the efficacy of chiropractic spinal manipulative therapy (CSMT) and the efficacy of Non-steroidal Anti-inflammatory Drugs (NSAIDs) on acute neck pain is unknown. This 4-arm randomized controlled trial (RCT) will likely provide evidence for the efficacy of CSMT as well as NSAIDs. The applied methodology of the study will aim towards the highest research standards possible for manual-therapy RCTs, thus avoiding typical methodological shortcomings from previous manual-therapy studies. Our aim is to establish evidence-based knowledge on the efficacy of CSMT and NSAIDs in the treatment of acute neck pain.

Detailed description: The Global Burden of Disease study ranks musculoskeletal neck pain as the most common disability worldwide. This study will highlight and validate CSMT for acute neck pain, compared to sham manipulation, ibuprofen and placebo medication. NSAIDs are the most frequently prescribed medications by GPs worldwide and are widely used for patients with back pain. However, evidence-based data are missing for acute neck pain patients treated with NSAIDs while existing evidence for CSMT for acute neck pain are limited by serious methodological shortcomings.

The 4-arm placebo-controlled RCT will assess the efficacy in the following four treatment groups:

1. Chiropractic spinal manipulative therapy (CSMT)
2. CSMT sham manipulation (placebo)
3. Ibuprofen (NSAID)
4. Placebo medication

We intend to invite 40 recruiting chiropractors from larger Norwegian cities, distributed by gender and geography. The study participants presenting to each chiropractor will be block-randomized equally into one of four study groups based on a computer-generated algorithm. Each chiropractor will include 16 participants, four into each arm. A total of 320 participants will be enrolled in the RCT, within 12 months. Participants randomized into the chiropractic treatment groups will receive 5 interventions over 12 days, i.e., CSMT or CSMT sham manipulation; while the pharmacological groups will receive 600mg ibuprofen or placebo administered 3 times daily for 12 days.

Eligibility criteria: Inclusion criteria

1. Eligible participants are between the age of 18 and 59 years old
2. Acute non-radicular neck pain, i.e., grade 1 or 2 according to the classification by the Bone and Joint Decade 2000-2010 Task Force on neck pain
3. Onset of the present episode ≤2 weeks prior to the 1st chiropractic visit
4. Moderate, severe or very severe pain intensity, i.e., ≥4, on a numeric rating scale (NRS) 0-10
5. Pain free for at least four consecutive weeks prior to the present pain episode
6. Not treated by a chiropractor during the past 3 months
7. Participants must accept not to seek other manual and/or pharmacological treatments for their acute neck pain during the intervention period
8. Non-pregnant women. Women in doubt shall have a negative fertility test before inclusion

Exclusion criteria

1. Contraindication to ibuprofen

   1. active peptic ulcer
   2. gastrointestinal bleeding
   3. previous repeated episode (≥2 detected events) with peptic ulcer or gastrointestinal bleeding
   4. previous gastrointestinal bleeding or ulcer using NSAIDs
   5. hypersensitivity to ibuprofen
   6. asthma induced by acetylsalicylic acid or other NSAIDs
   7. urticarial
   8. rhinitis
   9. severe heart failure (NYHA class IV)
   10. renal failure (glomerulus infusion \<30 ml/min)
2. Taken pain- and/or anti-inflammatory medicine during the past 24 hours? (Patients that have taken acute pain- and/or anti-inflammatory medicine, including ibuprofen, can be included if they come back after 24 hours without having taken the medicine where they then fill out questionnaires and are randomized at the clinic)
3. On prescribed antidepressant
4. Major psychiatric disorder
5. Pregnancy or intention to be pregnant
6. Contraindication to SMT
7. Signs of spinal radiculopathy including progressive neurological deficit
8. Upper cervical spine instability (positive Sharp-Purser test)
9. Previous fracture in the cervical and/or thoracic spine
10. Previous cervical spine surgery
11. Recent (\<6 months) severe physical trauma to the head, neck or thoracic spine within the previous 6 months
12. Concomitant low back pain with moderate, severe or very severe pain intensity (≥4 on a NRS)
13. Current chronic pain (defined as ≥3 months duration)
14. Rheumatoid arthritis
15. Recent (\<2 weeks) acute respiratory infection with fever
16. Any presence of ischemic symptoms upon examination
17. Horner's syndrome
18. Medical history of arterial anomalies
19. History of connective tissue disorder
20. Familial history of cervical artery dissection
21. Other vascular disorders
22. Inability to understand instructions given in the Norwegian language
23. Inability to fill out digital questionnaires
24. Other reasons to exclude the patient as deemed necessary by the chiropractor

Primary outcomes:
measure: Mean pain intensity change
timeFrame: From Day-0 to Day-14 between CSMT and sham CSMT, CSMT and ibuprofen, and CSMT and placebo medicine.
Secondary outcomes:
measure: Mean pain intensity change
timeFrame: From Day-0 to Day-14. Comparison between ibuprofen and placebo medicine.
measure: Mean pain intensity change
timeFrame: From Day-0 to Day 2-13 in the treatment period, and from Day-0 to Day 7, 28, 56, 84 and 168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Mean duration (hours) of neck pain change
timeFrame: From Day-0 to Day 2-13 and 14; From Day-0 to Day 7, 28, 56, 84 and 168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Mean number of days with neck pain per week
timeFrame: From the treatment period (14 days) to the periods; day 1-7, 22-28, 50-56, 78-84 and 162-168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Proportions of participants with mean daily pain intensity reduction of ≥50%, ≥75% and 100%
timeFrame: From Day-0 to Day 2-13 and 14, and from Day-0 to Day 7, 28, 56, 84 and 168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Proportions of participants with mean duration (hours) reduction of ≥50%, ≥75% and 100%
timeFrame: From Day-0 to Day 2-13 and 14, and from Day-0 to Day 7, 28, 56, 84 and 168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Proportions of participants with mean reduction of number of days with neck pain per week of ≥50%, ≥75% and 100%
timeFrame: From the treatment period (14 days), to the periods: Day 1-7, 22-28, 50-56, 78-84 and 162-168 post-treatment, respectively, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine
measure: Improvement in Research and development 12 (RAND-12) score (12 questions each with 5 possible answers)
timeFrame: From Day-0 to Day-14, Day-84 and 168 post-treatment, respectively, comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Improvement in Neck Disability Index score (10 questions each with 6 possible answers)
timeFrame: From Day-0 to Day-14, Day-84 and 168 post-treatment, respectively, comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Adverse event (AE) analysis
timeFrame: Daily during intervention period (day 2-13). AE analysis of CSMT, sham CSMT, ibuprofen, and placebo medicine, and comparison between CSMT and sham CSMT, CSMT and ibuprofen, CSMT and placebo medicine, ibuprofen and placebo medicine.
measure: Analysis of patients' blinding (Manual therapy)
timeFrame: Daily during intervention period (Day-0, Day 2-13). Analysis of CSMT and sham CSMT, and comparison between CSMT and sham CSMT.
measure: Analysis of patients' blinding (Medicine)
timeFrame: Daily during intervention period (Day-0, Day 2-13). Analysis of ibuprofen and placebo medicine, and comparison between ibuprofen and placebo medicine.
measure: Patients' and chiropractors' expectations to treatment efficacy
timeFrame: Day-0
measure: Analysis of patients' satisfaction to treatment efficacy
timeFrame: Day-14 of the intervention period
Other outcomes:
measure: Sick leave
timeFrame: Mean number of days at Day-0 compared to Week-12 and Week-24 post-treatment.
measure: Validation of user ID-number
timeFrame: All digital questionnaires from Day-0 to study completion, that is to 24-weeks follow-up.
measure: Facilitatory/inhibitory factors/dilemmas affecting recruitment Qualitative focus group interviews to explore facilitatory/inhibitory factors and possible dilemmas experienced by chiropractor investigators.
timeFrame: Up to 6 months
Locations:
city: Oslo
country: Norway
facility: Michael B. Russell
Study officials:
affiliation: Division for Research and Innovation, Akershus University Hospital, Norway
name: Michael B. Russell, Professor
role: STUDY_DIRECTOR
affiliation: Institute for Health and Society, Faculty of Medicine, University of Oslo, Norway
name: Aleksander Chaibi, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chaibi A, Stavem K, Russell MB. Spinal Manipulative Therapy for Acute Neck Pain: A Systematic Review and Meta-Analysis of Randomised Controlled Trials. J Clin Med. 2021 Oct 28;10(21):5011. doi: 10.3390/jcm10215011.
citation: Chaibi A, Saltyte Benth J, Bjorn Russell M. Validation of Placebo in a Manual Therapy Randomized Controlled Trial. Sci Rep. 2015 Jul 6;5:11774. doi: 10.1038/srep11774.