Multiple Sclerosis, Relapsing-RemittingNCT04972929
Effects of Chiropractic Care on Cytokine Levels in Multiple Sclerosis
A study testing Spinal Manipulation in people with Multiple Sclerosis, Relapsing-Remitting, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
Multiple sclerosis (MS) is an inflammatory autoimmune disease associated with an imbalance between pro- and anti-inflammatory markers (cytokines) resulting in a demyelinating and neurodegenerative disease. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- What is being tested?
- Spinal Manipulation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Sep 2023to 12 Mar 2025
- Phase
- Interventional
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18 to 55 years
- Physician-confirmed diagnosis of MS within the last 5 years
- Expanded Disability Status Scale (EDSS) score below 4 based on Neurostatus-certified examination
- Relapse free in the last 30 days
- No known cardiovascular, pulmonary, or metabolic disease
- Currently on stable FDA-approved disease modifying therapy (eg, interferon beta-1a or beta-1b, natalizumab etc.)
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- Naïve to chiropractic care
- No contraindications to spinal manipulation
- Acceptance of informed consent.
Who cannot join
- Uncontrolled hypertension (systolic pressure >160 mmHg, diastolic blood pressure >95 mmHg) Any past spinal surgery or recent history of bone fractures
- Pregnancy in the last 12 months
- Unable to understand English or follow simple instruction.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294
About this study
Official title: Effects of Chiropractic Care on Pro- and Anti-inflammatory Cytokine Levels in Multiple Sclerosis
Multiple sclerosis (MS) is an inflammatory autoimmune disease associated with an imbalance between pro- and anti-inflammatory markers (cytokines) resulting in a demyelinating and neurodegenerative disease. There is early evidence that spinal manipulation (chiropractic care) is better than control in influencing immune (cytokine) activity in asymptomatic participants, but few studies have been completed in participants with chronic inflammatory conditions, such as MS. The purpose of this project is to examine the immediate (after a single thoracic spinal manipulation treatment) and summative impact (after 8 thoracic spinal manipulation treatments occurring over 4 weeks) on pro-inflammatory (interleukin (IL) IL-1ß, IL-2, IL-6, Tumor necrosis factor-alpha) and anti-inflammatory (IL-4, IL-10) plasma cytokines 20 minutes and 2 hours after thoracic spinal manipulation in participants diagnosed with neuroinflammatory relapsing-remitting MS (RR-MS). Spinal manipulation treatment will be limited to the thoracic spine. Secondary outcomes will include determining the impact of 8 thoracic spinal manipulations on fatigue, cognitive processing speed, pain, depression, sleep, and motor function through questionnaires and performance of various in assessments such as the timed 25 foot walk test.
Read the detailed description
Study Design. The investigators plan to conduct a pilot parallel-group randomized controlled trial with appropriate SM and Sham SM treatment groups. Randomization will occur with the sequence being completed prior to enrolling the first participant and with concealed allocation by a member of the team not involved with the outcomes or treatments. The investigators designed the Sham SM treatments to ensure all participants have similar amounts of physical contact and clinician interaction (i.e. contextual environment for placebo-related improvement). The primary and secondary outcomes of the study will be assessed and processed by blinded assessors who are not part of the intervention delivery to reduce any potential bias in collected outcomes.
SM Delivery. Diversified (i.e. crossed bilateral hypothenar contact) chiropractic technique will be administered at levels of identified spinal joint restriction/dysfunction (derived from thoracic spine x-rays, static and motion palpation, and confirmed or provoked localized tenderness in paraspinal soft tissues). Participants in the SM and Sham SM group will be scheduled for 8 office visits (2x/wk) over a period of 4 weeks.
The Sham-SM will be delivered by setting the expansion control knob on an Activator II (Activator Methods®, Phoenix AZ) device to the zero position (off; no thrust) and placed onto the dorsal thumb surface of the clinician (no actual instrument contact with study participant). At a setting of zero, no excursion of the Activator II stylus occurs, despite the device delivering an audible clicking sound, with no biomechanical force being imparted to the participant.
Primary Outcome Variable. To examine the immediate (1x) and summative impact of SM (8x/4wk) on pro-inflammatory and anti-inflammatory plasma cytokine levels at 20 minutes and 2 hours post-SM (after the first and 8th treatment) and compared to baseline measures.
Secondary Outcome Variables. To examine the summative and secondary impact of 8 chiropractic treatments over 4 weeks on RR-MS-related fatigue (Fatigue Severity Scale, Modified Fatigue Impact Scale), cognitive processing speed (Symbol Digit Modalities Test), pain (short-form McGill Pain Questionnaire), depression (Hospital Anxiety Depression Scale), subjective sleep (Insomnia Severity Index) and upper/lower body motor function (Nine-Hole Peg Test, Timed 25 foot Walk Test). These secondary outcomes will be measured before onset of treatment (baseline) and upon completion of 8 spinal manipulation treatments over the period of 4 weeks) (2 visits per week).
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- Spinal Manipulation, Sham Spinal Manipulation
- Keywords
- chiropractic, spinal manipulation, multiple sclerosis, cytokines
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting, Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Spinal ManipulationOther
Also called chiropractic care
Diversified (i.e. crossed bilateral hypothenar contact) chiropractic technique will be administered at levels of identified spinal joint restriction/dysfunction (derived from thoracic spine x-rays, static and motion palpation, and confirmed or provoked localized tenderness in paraspinal soft tissues).
Sham Spinal ManipulationOther
Sham-SM will be delivered by setting the expansion control knob on an Activator II (Activator Methods®, Phoenix AZ) device to the zero position (off; no thrust) and placed onto the dorsal thumb surface of the clinician (no actual instrument contact with study participant). At a setting of zero, no excursion of the Activator II stylus occurs, despite the device delivering an audible clicking sound, with no biomechanical force being imparted to the participant.
| Study group | Role | What they receive |
|---|---|---|
| Spinal Manipulation | Experimental | The spinal manipulation (SM) group will receive manually delivered SM limited to the thoracic spine. Receives: Other: Spinal Manipulation |
| Sham Spinal Manipulation | Sham comparator | Sham-spinal manipulation will be delivered by setting the expansion control knob on an Activator II (Activator Methods®) device to the zero position (off; no thrust) and placed onto the dorsal thumb surface of the clinician. At a setting of zero, no excursion of the Activator II stylus occurs, despite the device delivering an audible clicking sound, with no biomechanical force being imparted. Receives: Other: Sham Spinal Manipulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
IL-6 Serum Inflammatory Cytokine Levels
Determined mean changes in serum inflammatory cytokine levels from baseline for each group
Measured: From baseline to after 8th treatment at 4 weeks
IL-4 Serum Inflammatory Cytokine Levels
Determine changes in serum inflammatory cytokine levels from baseline
Measured: From baseline to after 8th treatment at 4 weeks
IL-10 Serum Inflammatory Cytokine Levels
Determine changes in serum inflammatory cytokine levels from baseline
Measured: From baseline to after 8th treatment at 4 weeks
IL-2 Serum Inflammatory Cytokine Levels
Determine changes in serum inflammatory cytokine levels from baseline
Measured: From baseline to after 8th treatment at 4 weeks
TNFalpha Serum Inflammatory Cytokine
Determine changes in serum inflammatory cytokine levels from baseline
Measured: baseline to after 8th treatment at 4 weeks
IL-B Serum Cytokine Levels
Mean change in serum from baseline and after 8 treatments
Measured: baseline and 8th treatment after 4 weeks
Secondary outcomes (8)
Fatigue Severity Scale (FSS)
Determine changes in fatigue from baseline. It is a 9 item scale determining fatigue severity and its effect on a person's activities.
The 9-item Fatigue Severity Scale (FSS) is a self-report questionnaire designed to measure the severity of fatigue and its impact on daily functioning over the past week. Respondents rate nine statements on a 7-point Likert scale (1 = strongly disagree, 7 = strongly agree). The scores for the nine statements are averaged to compute a total score ranging from 1 to 7, with higher average scores indicating greater fatigue severity.
Measured: From Baseline to after 8th treatment at 4 weeks
Modified Fatigue Impact Scale
Determine changes in fatigue and tiredness from baseline. It is a 21 item scale that provides a more in-depth look at the impact of fatigue and lack of energy might have on mental alertness and daily activities. It evaluates three domains: physical, cognitive, and psychosocial functioning, typically over the past 4 weeks, with a total score range of 0-84 (higher number indicate greater fatigue)
Measured: From baseline to after 8th treatment at 4 weeks
Cognitive Processing Speed
Determine changes in cognitive (rapid) processing speed from baseline. Assesses the time it takes to complete a mental task and is related to the speed at which a person can understand and react to a set of information that they receive.
Measured: From Baseline to after 8th treatment at 4 weeks
Total Change in Pain Short-form McGill Pain Questionnaire
The McGill Pain Questionnaire (MPQ) is a multidimensional self-report tool used to evaluate the quality, location, and intensity of a patient's pain. The mean change in pain scores will be totaled on a scale of 0-3, where 3 equals more severe pain on 15 separate items totaled to compute a total minimum score of 0 and maximum score of 45.
Measured: From Baseline to after 8th treatment at 4 weeks
Total Change in Hospital Anxiety Depression Scale
Determine changes in anxiety/depression from baseline. This is a 14 item instrument that you respond to inquires related about you have felt during the last week.The total score is out of 0-42, (0-21 per subscale). Total Scores are derived by summing responses for each of the two subscales or for the scale as a whole. Higher scores indicate greater levels of anxiety or depression.
Measured: From Baseline to after 8th treatment at 4 weeks
Insomnia Severity Index
Determine changes in sleep quality from baseline. This is a 7 item instrument to assess components of nighttime and daytime insomnia. The Insomnia Severity Index (ISI) is a 7-item, self-report questionnaire used to assess the severity of insomnia, with a total score ranging from 0-28. A score of 15 or higher is typically used to indicate moderate-to-severe clinical insomnia, with 8-14 indicating subthreshold insomnia.
Measured: From Baseline to after 8th treatment at 4 weeks
Nine-Hole Peg Test
Determine changes in upper limb coordination from baseline. This is a standardized timed assessment to assess finger dexterity in which 9 wooden pegs are placed into predrilled holes in a block of wood.
Measured: From Baseline to after 8th treatment at 4 weeks
Timed 25 Foot Walk Test
Determine changes in lower limb mobility from baseline. Evaluates leg function and quantitative mobility in a timed 25 foot walk.
Measured: From Baseline to after 8th treatment at 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2021
- Study start15 Sep 2023
- Primary completion12 Mar 2025
- Study completion12 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- 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
- Model description
- e plan to conduct a randomized pilot parallel-group randomized controlled trial (RCT) with appropriate SM and Sham SM treatment groups.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, William R Reed DC, PhD, University of Alabama at Birmingham
- Investigators
- William R Reed, DC, PhD, Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04972929
- Sponsor's protocol ID
- IRB-300007021
- Other IDs
- TRG2020
- Status last verified
- Jul 2026
- First submitted
- 27 Apr 2021
- Last updated
- 20 Jul 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Alanazi MS, Motl RW, Jones BA, Qu H, Li P, Reed WR. Effects of thoracic manipulation with trigger point therapy on inflammatory cytokine levels in individuals with multiple sclerosis: a pilot study. Front Rehabil Sci. 2026 Apr 8;7:1699274. doi: 10.3389/fresc.2026.1699274. eCollection 2026.
PubMed 42028147