NCT04972929

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Sep 2023

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 27, 2021

Completed
3 months until next milestone

First Posted

Study publicly available on registry

July 22, 2021

Completed
2.2 years until next milestone

Study Start

First participant enrolled

September 15, 2023

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 12, 2025

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 12, 2025

Completed
1.4 years until next milestone

Results Posted

Study results publicly available

July 20, 2026

Completed
Last Updated

July 20, 2026

Status Verified

July 1, 2026

Enrollment Period

1.5 years

First QC Date

April 27, 2021

Results QC Date

March 9, 2026

Last Update Submit

July 17, 2026

Conditions

Multiple Sclerosis, Relapsing-Remitting

Keywords

chiropracticspinal manipulationmultiple sclerosiscytokines

Outcome Measures

Primary Outcomes (6)

  • IL-6 Serum Inflammatory Cytokine Levels

    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

    Determine changes in serum inflammatory cytokine levels from baseline

    From baseline to after 8th treatment at 4 weeks

  • IL-10 Serum Inflammatory Cytokine Levels

    Determine changes in serum inflammatory cytokine levels from baseline

    From baseline to after 8th treatment at 4 weeks

  • IL-2 Serum Inflammatory Cytokine Levels

    Determine changes in serum inflammatory cytokine levels from baseline

    From baseline to after 8th treatment at 4 weeks

  • TNFalpha Serum Inflammatory Cytokine

    Determine changes in serum inflammatory cytokine levels from baseline

    baseline to after 8th treatment at 4 weeks

  • IL-B Serum Cytokine Levels

    Mean change in serum from baseline and after 8 treatments

    baseline and 8th treatment after 4 weeks

Secondary Outcomes (8)

  • Fatigue Severity Scale (FSS)

    From Baseline to after 8th treatment at 4 weeks

  • Modified Fatigue Impact Scale

    From baseline to after 8th treatment at 4 weeks

  • Cognitive Processing Speed

    From Baseline to after 8th treatment at 4 weeks

  • Total Change in Pain Short-form McGill Pain Questionnaire

    From Baseline to after 8th treatment at 4 weeks

  • Total Change in Hospital Anxiety Depression Scale

    From Baseline to after 8th treatment at 4 weeks

  • +3 more secondary outcomes

Study Arms (2)

Spinal Manipulation

EXPERIMENTAL

The spinal manipulation (SM) group will receive manually delivered SM limited to the thoracic spine.

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.

Other: Sham Spinal Manipulation

Interventions

Spinal ManipulationOTHER

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).

Also known as: chiropractic care
Spinal Manipulation
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.

Sham Spinal Manipulation

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Related Publications (1)

  • 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.

    PMID: 42028147DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-RemittingMultiple Sclerosis

Interventions

Manipulation, Spinal

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System Diseases

Intervention Hierarchy (Ancestors)

Musculoskeletal ManipulationsPhysical Therapy ModalitiesTherapeuticsRehabilitation

Limitations and Caveats

Limitations include: the exploratory nature and small sample size (n=21) of this pilot study which was not adequately powered for hypothesis testing, but designed to inform for future studies; the timing of blood collection at 20 minutes and 2 hours post-intervention may not have captured the immediate, earliest or most relevant changes in cytokine/chemokine levels related to spinal manipulation/trigger point therapy.

Results Point of Contact

Title
Dr. William R. Reed (professor)
Organization
University of Alabama at Birmingham
wreed@uab.edu
2059343261

Study Officials

  • William R Reed, DC, PhD

    University of Alabama at Birmingham

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
The chiropractic clinician will not be blinded in order to deliver the assigned treatment (spinal manipulation or Sham spinal manipulation) but all other assessors and study personnel will be blinded to the group assignment.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: e plan to conduct a randomized pilot parallel-group randomized controlled trial (RCT) with appropriate SM and Sham SM treatment groups.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

April 27, 2021

First Posted

July 22, 2021

Study Start

September 15, 2023

Primary Completion

March 12, 2025

Study Completion

March 12, 2025

Last Updated

July 20, 2026

Results First Posted

July 20, 2026

Record last verified: 2026-07

Locations

US(1)