Multiple Sclerosis
Conditions
Keywords
Chronic pain, Cognitive behavioral therapy, Multiple sclerosis, Randomized controlled trial
Brief summary
The purpose of this study is to evaluate the efficacy of a brief psychological intervention, cognitive-behavior therapy, for the management of persistent pain associated with Multiple Sclerosis.
Detailed description
The primary purpose of the proposed study is to evaluate the feasibility and efficacy of tailored CBT with standard pharmaceutical care (CBT/SC) in reducing pain, disability, and distress among persons with Multiple Sclerosis (MS) related pain conditions. This will entail: (1) evaluating the feasibility, perceived credibility, participation and adherence rates, and satisfaction related to CBT, (2) conducting a randomized controlled trial of the efficacy of CBT relative to an education control/standard care (ED/SC) condition, and (3) evaluating possible predictors of treatment response including demographics, disease-relevant variables, cognitive functioning, and motivation or readiness to adopt a self-management approach to MS-related pain. Research Design: A randomized mixed factorial controlled design will be employed in which CBT/SC is compared to EDSC. Repeated assessments of key outcome domains will occur at pretreatment/baseline, at 15 weeks (post-treatment), and 20, 36, and 52 (follow-up) weeks. Methodology: Participants in this trial will be 124 persons with MS (including veterans and non-veterans) who report persistent MS-related pain (e.g., neuropathic pain, pain related to muscle spasms, neuralgias) of at least moderate intensity (pain severity of 4 or greater on the numeric rating scale) despite optimal pharmacological management. Participants must be at least 21 years of age and able to provide informed consent. Exclusion criteria include: (1) pending surgery or interventional anesthesiological procedures for pain, (2) currently psychotic or actively suicidal or homicidal, (3) current alcohol or substance abuse or dependence, (4) presence of other life threatening illnesses, (5) the presence of profound cognitive impairment rendering successful participation in CBT or ED impossible, (6) the presence of physical disabilities resulting in an inability to attend treatment sessions and/or inability to participate in telephone interventions (e.g., severe dysarthria), (7) prior or current psychological treatment for chronic pain, (8) two or more documented exacerbations of MS-related symptoms during the past year, and (9) current exacerbation of symptoms defined as sudden onset of symptoms within a 24 hour period. CBT will involve an innovative treatment approach that combines specific training in relevant cognitive and behavior skills targeting management of pain and the negative impacts of pain. The application of these skills for the management of coincident symptoms of MS (e.g., spasticity, fatigue, abnormal sensory experiences) will also be encouraged. ED will involve provision of a broad array of educational material regarding MS and its management, but it will not explicitly inform participants about non-pharmacological strategies for management of pain. Both treatments will involve seven 60 minute, outpatient individual treatment sessions offered every other week, interspersed with five, 30 minute individual telephone sessions (one final face-to-face session will be 30 minute individual telephone sessions will be included) provided by a psychologist and supported by patient education and treatment guides that have been developed for the study. Participants will be randomly assigned to one of two treatment arms: CBT/SC or ED/SC. Recruitment rates, session adherence, dropout rates, and participants' ratings of comprehension, treatment credibility, treatment satisfaction and adherence to therapist recommendations will be used to assess feasibility of the treatment and recruitment methods. Multiple standardized measures of each outcome domain of interest will be obtained, including pain severity, disability, affective distress, and quality of life. The analysis of each of the primary and secondary outcome measures (summary measures of pain intensity, pain-related disability, MS-related disability, and emotional functioning) will be by a repeated measures mixed effects model27. The outcome variable in each model will be the changes at each follow-up visit relative to baseline, with the baseline value included as a covariate in the model. Several possible predictors of treatment adherence and outcome will be examined, including participant demographics (e.g., age, gender, ethnicity), disease-relevant variables (e.g.., MS subtype, disease duration, disease severity, level of cognitive functioning), outcome measures (e.g., pain severity, depressive symptom severity), and a measure of motivation for adoption of a self-management approach to chronic pain.
Interventions
BEHAVIORALCognitive-behavior therapy
CBT: The components of CBT include (1) identification of idiosyncratic beliefs about pain and pain treatment, as well as reconceptualization of the pain experience as subject to personal control (sessions 1-2), (2) instruction in specific cognitive (e.g., distraction) and behavioral (e.g., change in activity patterns such as alternating activity with periods of rest) skills (sessions 3-8), and (3) consolidation of cognitive/behavioral skills through activities such as role playing (sessions 9-11).
OTHERInterventional
Educational intervention: Session topics will include information on the etiology of MS, MS subtypes and disease progression, common symptoms of MS, medical management of MS, rehabilitation approaches to management of MS-related symptoms, exercise, sick day management, stress management, psychosocial adjustment, family involvement, and appropriate use of the health care system.
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* a confirmed diagnosis of Multiple Sclerosis, * history of daily pain or discomfort (burning, tingling or other parenthesis) for a period of 3 months immediately prior to enrollment, * judgment of one of the study neurologists (AL or MK) that the pain reported by the patient is either directly \[e.g., pain associated with optic neuritis and neuralgias\] or indirectly related \[e.g., pain due to painful muscle contractures and spasms\] to MS and/or its treatment (persons with pain that is judged to be entirely coincident with MS \[e.g., idiopathic low back pain\] will not be included), * documentation of optimal pharmacological management of MS-related pain and confirmation of this judgment by one of the study neurologists, * continued use of appropriate pharmaceuticals for the management of MS and pain, and * continued refractory pain despite pharmaceutical intervention as described above (as determined by a pain intensity score 4 on a 0-10 numeric rating scale).
Exclusion criteria
* pending surgery or interventional anesthesiological procedures for pain, * currently psychotic or actively suicidal or homicidal, * current alcohol or substance abuse or dependence, * presence of other life threatening illnesses, * the presence of profound cognitive impairment rendering successful participation in CBT or ED impossible, * the presence of physical disabilities resulting in an inability to attend treatment sessions and/or inability to participate in telephone interventions (e.g., severe dysarthria), * prior or current psychological treatment for chronic pain, * two or more documented exacerbations of MS-related symptoms during the past year, and * current exacerbation of symptoms defined as sudden onset of symptoms within a 24 hour period. Participants experiencing an exacerbation will be included after a one-month period of appropriate treatment or three months after the onset of the exacerbation. The Exacerbation Questionnaire, also described below and developed by Dr. Mohr, one of our co-investigators, will be used to assess and monitor significant exacerbations of MS. The Multiple Sclerosis Functional Composite (MSFC) score described below will be used to determine these later two
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain Intensity | baseline | The Numeric Rating Scale of pain intensity (NRS-I) is an 11-point numeric rating scale (0 = no pain, 10 = worst pain imaginable). Participants were asked to rate their usual, worst and least pain over the past week. The average of these numbers will serve as the primary outcome measure. |
Countries
United States
Participant flow
Recruitment details
Recruitment occured during April 2007 through September 2009. Participants were Veterans and nonVeterans recruited primarily through their providers in one of three treatment settings, namely the MS Clinics at the VA Connecticut Healthcare System and VA Boston Healthcare System and at the Yale MS Center.
Pre-assignment details
1 subject enrolled into the study but was found to be ineligible before randomization.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive-behavior Therapy Behavioral: Cognitive-behavior therapy
Cognitive-behavior therapy: CBT: The components of CBT include (1) identification of idiosyncratic beliefs about pain and pain treatment, as well as reconceptualization of the pain experience as subject to personal control (sessions 1-2), (2) instruction in specific cognitive (e.g., distraction) and behavioral (e.g., change in activity patterns such as alternating activity with periods of rest) skills (sessions 3-8), and (3) consolidation of cognitive/behavioral skills through activities such as role playing (sessions 9-11). | 13 |
| Educational Intervention Interventional: Educational intervention
Interventional: Educational intervention: Session topics will include information on the etiology of MS, MS subtypes and disease progression, common symptoms of MS, medical management of MS, rehabilitation approaches to management of MS-related symptoms, exercise, sick day management, stress management, psychosocial adjustment, family involvement, and appropriate use of the health care system. | 12 |
| Total | 25 |
Baseline characteristics
| Characteristic | Educational Intervention | Total | Cognitive-behavior Therapy |
|---|---|---|---|
| Age, Continuous | 54.67 Years STANDARD_DEVIATION 12.361 | 53.95 Years STANDARD_DEVIATION 10.408 | 53.23 Years STANDARD_DEVIATION 8.691 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 4 Participants | 9 Participants | 5 Participants |
| Sex: Female, Male Male | 8 Participants | 16 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 13 | 0 / 12 |
| serious Total, serious adverse events | 0 / 13 | 0 / 12 |
Outcome results
Primary
Pain Intensity
The Numeric Rating Scale of pain intensity (NRS-I) is an 11-point numeric rating scale (0 = no pain, 10 = worst pain imaginable). Participants were asked to rate their usual, worst and least pain over the past week. The average of these numbers will serve as the primary outcome measure.
Time frame: baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive-behavior Therapy | Pain Intensity | 5.31 units on a scale | Standard Deviation 2.213 |
| Educational Intervention | Pain Intensity | 5.42 units on a scale | Standard Deviation 2.61 |
p-value: 0.91195% CI: [-2.106, 1.888]t-test, 2 sided
Primary
Pain Intensity
The Numeric Rating Scale of pain intensity (NRS-I) is an 11-point numeric rating scale (0 = no pain, 10 = worst pain imaginable). Participants were asked to rate their usual, worst and least pain over the past week. The average of these numbers will serve as the primary outcome measure.
Time frame: Baseline to Post Treatment (12 weeks)
Population: Multiple imputation used to account for missing variables; pre-treatment rating and years of MS pain were covariates
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cognitive-behavior Therapy | Pain Intensity | 5.76 units on a scale | Standard Deviation 1.53 |
| Educational Intervention | Pain Intensity | 5.12 units on a scale | Standard Deviation 2.51 |
p-value: 0.3295% CI: [-1.058, 2.345]ANCOVA