Effects of Chiropractic Care on Cytokine Levels in Multiple Sclerosis

July 17, 2026 updated by: William R Reed DC, PhD, University of Alabama at Birmingham

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Actual)

26

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 Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham

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

14 years to 51 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.)
  • Naïve to chiropractic care
  • No contraindications to spinal manipulation
  • Acceptance of informed consent.

Exclusion criteria include:

  • 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.

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: Spinal Manipulation
The spinal manipulation (SM) group will receive manually delivered SM limited to the thoracic spine.
Other: Spinal Manipulation
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).
Other Names:
  • chiropractic care
Sham Comparator: Sham Spinal Manipulation
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.
Other: Sham Spinal Manipulation
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
IL-6 Serum Inflammatory Cytokine Levels
Time Frame: From baseline to after 8th treatment at 4 weeks
Determined mean changes in serum inflammatory cytokine levels from baseline for each group
From baseline to after 8th treatment at 4 weeks
IL-4 Serum Inflammatory Cytokine Levels
Time Frame: From baseline to after 8th treatment at 4 weeks
Determine changes in serum inflammatory cytokine levels from baseline
From baseline to after 8th treatment at 4 weeks
IL-10 Serum Inflammatory Cytokine Levels
Time Frame: From baseline to after 8th treatment at 4 weeks
Determine changes in serum inflammatory cytokine levels from baseline
From baseline to after 8th treatment at 4 weeks
IL-2 Serum Inflammatory Cytokine Levels
Time Frame: From baseline to after 8th treatment at 4 weeks
Determine changes in serum inflammatory cytokine levels from baseline
From baseline to after 8th treatment at 4 weeks
TNFalpha Serum Inflammatory Cytokine
Time Frame: baseline to after 8th treatment at 4 weeks
Determine changes in serum inflammatory cytokine levels from baseline
baseline to after 8th treatment at 4 weeks
IL-B Serum Cytokine Levels
Time Frame: baseline and 8th treatment after 4 weeks
Mean change in serum from baseline and after 8 treatments
baseline and 8th treatment after 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Fatigue Severity Scale (FSS)
Time Frame: From Baseline to after 8th treatment at 4 weeks

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.
From Baseline to after 8th treatment at 4 weeks
Modified Fatigue Impact Scale
Time Frame: From baseline to after 8th treatment at 4 weeks
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)
From baseline to after 8th treatment at 4 weeks
Cognitive Processing Speed
Time Frame: From Baseline to after 8th treatment at 4 weeks
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.
From Baseline to after 8th treatment at 4 weeks
Total Change in Pain Short-form McGill Pain Questionnaire
Time Frame: From Baseline to after 8th treatment at 4 weeks
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.
From Baseline to after 8th treatment at 4 weeks
Total Change in Hospital Anxiety Depression Scale
Time Frame: From Baseline to after 8th treatment at 4 weeks
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.
From Baseline to after 8th treatment at 4 weeks
Insomnia Severity Index
Time Frame: From Baseline to after 8th treatment at 4 weeks
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.
From Baseline to after 8th treatment at 4 weeks
Nine-Hole Peg Test
Time Frame: From Baseline to after 8th treatment at 4 weeks
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.
From Baseline to after 8th treatment at 4 weeks
Timed 25 Foot Walk Test
Time Frame: From Baseline to after 8th treatment at 4 weeks
Determine changes in lower limb mobility from baseline. Evaluates leg function and quantitative mobility in a timed 25 foot walk.
From Baseline to after 8th treatment at 4 weeks

Collaborators and Investigators

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

Sponsor

University of Alabama at Birmingham

Investigators

  • Principal Investigator: William R Reed, DC, PhD, University of Alabama at Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

September 15, 2023

Primary Completion (Actual)

March 12, 2025

Study Completion (Actual)

March 12, 2025

Study Registration Dates

First Submitted

April 27, 2021

First Submitted That Met QC Criteria

July 12, 2021

First Posted (Actual)

July 22, 2021

Study Record Updates

Last Update Posted (Actual)

July 20, 2026

Last Update Submitted That Met QC Criteria

July 17, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB-300007021
  • TRG2020 (Other Grant/Funding Number: Australian Spinal Research Foundation)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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