Multiple Sclerosis, Relapsing-Remitting
Conditions
Keywords
chiropractic, spinal manipulation, multiple sclerosis, cytokines
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.
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).
Interventions
OTHERSpinal 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).
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.
Sponsors
University of Alabama at Birmingham
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
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.
Intervention model description
e plan to conduct a randomized pilot parallel-group randomized controlled trial (RCT) with appropriate SM and Sham SM treatment groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| IL-6 Serum Inflammatory Cytokine Levels | From baseline to after 8th treatment at 4 weeks | Determined mean changes in serum inflammatory cytokine levels from baseline for each group |
| IL-4 Serum Inflammatory Cytokine Levels | From baseline to after 8th treatment at 4 weeks | Determine changes in serum inflammatory cytokine levels from baseline |
| IL-10 Serum Inflammatory Cytokine Levels | From baseline to after 8th treatment at 4 weeks | Determine changes in serum inflammatory cytokine levels from baseline |
| IL-2 Serum Inflammatory Cytokine Levels | From baseline to after 8th treatment at 4 weeks | Determine changes in serum inflammatory cytokine levels from baseline |
| TNFalpha Serum Inflammatory Cytokine | baseline to after 8th treatment at 4 weeks | Determine changes in serum inflammatory cytokine levels from baseline |
| IL-B Serum Cytokine Levels | baseline and 8th treatment after 4 weeks | Mean change in serum from baseline and after 8 treatments |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fatigue Severity Scale (FSS) | 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. |
| Modified Fatigue Impact Scale | 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) |
| Cognitive Processing Speed | 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. |
| Total Change in Pain Short-form McGill Pain Questionnaire | 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. |
| Total Change in Hospital Anxiety Depression Scale | 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. |
| Insomnia Severity Index | 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. |
| Nine-Hole Peg Test | 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. |
| Timed 25 Foot Walk Test | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORWilliam R Reed, DC, PhD
University of Alabama at Birmingham
Participant flow
Recruitment details
People with RRMS were recruited through advertisements distributed on the UAB campus, the local chapter of the National Multiple Sclerosis Society as well via clinicians at the UAB Multiple Sclerosis Center. Recruitment began in September 2023 and data collection ended in February 2025. Sixty-six people with MS were screened for eligibility, 26 met the inclusion criteria and provided informed consent.
Pre-assignment details
Three participants withdrew before the baseline visit and two were excluded due to the physical exam/x-ray findings. All of the 21 participants that were included in the study completed the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 21 Participants |
| Age, Continuous | 44 years STANDARD_DEVIATION 8.9 |
| Race/Ethnicity, Customized Race black | 5 Participants |
| Race/Ethnicity, Customized Race Unknown | 1 Participants |
| Race/Ethnicity, Customized Race white | 8 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 0 / 11 | 0 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
None listed