Multiple Sclerosis
Conditions
Keywords
Stress, Stress Management, Behavioral Medicine, Multiple Sclerosis, Psychoneuroimmunology
Brief summary
There is a growing body of literature showing that stressful life events can increase the risk of developing exacerbations and new brain lesions among people with multiple sclerosis. The purpose of this study is to examine the hypothesis that stress management programs can reduce the occurrence of new brain lesions and exacerbations. We will also examine potential immune and neuroendocrine pathways.
Detailed description
MS is a frequently disabling autoimmune disease affecting approximately 350,000 people in the United States. More than two decades of research has consistently shown a relationship between stressful life events (SLEs), in particular non-traumatic family and work stressors, and subsequent clinical exacerbation. Furthermore, we have shown that non-traumatic SLEs increase the risk of the subsequent appearance of new gadolinium enhancing (Gd+) magnetic resonance imaging (MRI) brain lesions, an early marker of MS inflammation and blood-brain barrier (BBB) breakdown. The purpose of this study is to determine the efficacy of cognitive behavioral stress management for MS (CBSM-MS) in reducing the occurrence of new brain lesions in people with relapsing forms of MS. Patients must have a documented new Gd+ MRI brain lesion or clinical exacerbation within the previous 12 months to be enrolled. One hundred and twelve patients will be enrolled for 12 months. Patients will be randomly assigned to either an intensive CBSM-MS program, consisting of 16 individual meetings with a behavioral medicine specialist, or a condensed CBSM-MS program, consisting of a one-day workshop offered after the 10th month of participation. Outcomes include MRI, clinical neurological end-points, and psychosocial functioning. We will also enhance our understanding of mechanisms by examining potential psychosocial, immune, and endocrine mediators of the relationship between SLEs and clinical and neuroimaging markers of MS inflammation.
Interventions
BEHAVIORALIndividual Stress Management
Stress management therapy for multiple sclerosis (SMT-MS) is a manualized, validated, published stress management program designed for patients with MS. Participants met with a therapist for 16 individual 50-minute sessions conducted over 20-24 weeks. The first 6 sessions focused on teaching problem solving skills, relaxation, increasing positive activities, cognitive restructuring, and enhancement of social support. Participants were able to tailor the treatment to meet their needs using optional treatment modules including communication and assertiveness training, fatigue management, anxiety reduction, pain management, management of cognitive problems, insomnia treatment, and management of sexual dysfunction.
OTHERWait List Control
Wait List Control provided treatment as usual for the first 10+ months of participation. A 5-hour workshop was provided after the 10th month. This allowed at least 2 post-treatment MRI evaluation that were not contaminated by the workshop.
Sponsors
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Northwestern University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Confirmed diagnosis of MS * New Gd+ MRI brain lesion or clinically diagnosed exacerbation within the previous 12 months. * Able to speak english. * Age 18 or over. * Able to give informed consent. * Patients taking the drug glatiramer acetate must have been on the drug for at least 6 months prior to their Gd+ MRI brain lesion and/or exacerbation. * Patients taking an interferon beta drug must have been on the drug for at least 1 month prior to their Gd+ MRI brain lesion and/or exacerbation. * Patients not on disease modifying treatment are not planning to initiate treatment.
Exclusion criteria
* Meets criteria for dementia by scoring below the 5th percentile in 3 or more of 6 areas of neuropsychological functioning or as determined by study neuropsychologist. * Severe psychiatric pathology, including schizophrenia, bipolar disorder, current alcoholism or substance abuse, or other severe psychiatric disorder for which this intervention would be inappropriate. * Active and severe suicidal ideation. * Endocrine or metabolic disorder. * Currently in psychotherapy. * Initiated antidepressant therapy within the past 4 weeks. * Received corticosteroid treatment within the past 28 days. * Pregnant or planning pregnancy in the next 12 months. * Has any non-removable metal or medical device in the body for which an MRI could pose a danger. * Has any risk factors for developing nephrogenic systemic fibrosis (NSF) or is allergic to Gadolinium. * Currently uses a Baclofen pump. * Has an Expanded Disability Status Scale score greater than 6.5. * Recently begun relaxation, meditation, yoga, or similar form of disease management course within the past 3 months. * Treatment with Chemotherapy. * Treatment with Tysabri.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| No.of Gd+ Lesions From Week 8 to Week 24 | week 8 to week 24 | Gd+ is Gadolinium-enhancing MRI brain lesion, A marker of the opening of the blood-brain barrier and is typically used as a primary endpoints in phase II trials because of its high sensitivity to ongoing MS disease activity and its association with clinical exacerbation. The single value was calculated by summing up the lesions from week 8 to week 24. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | week 8 to week 24 | T2-weighted MRI is commonly used in phase II trials to identify more permanent lesions. The single value was calculated by summing up the lesions from week 8 to week 24. |
Countries
United States
Participant flow
Recruitment details
Participants were enrolled at MS specialty clinics at three sites in the United States (University of California San Francisco California (UCSF), Evergreen Hospital Medical Center in Seattle Washington and the Feinberg School of Medicine at Northwestern University in Chicago Illinois) and through local chapters of the National MS Society.
Participants by arm
| Arm | Count |
|---|---|
| Stress Management Therapy for Multiple Sclerosis Stress management therapy for multiple sclerosis(SMT-MS)at baseline | 60 |
| Wait List Control Condition Wait list control provided treatment as usual for the first 10+ months of participation. A 5-hour workshop was provided after the 10th month. This allowed at least 2 post-treatment MRI evaluations that were not contaminated by the workshop | 61 |
| Total | 121 |
Baseline characteristics
| Characteristic | Wait List Control Condition | Stress Management Therapy for Multiple Sclerosis | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 58 Participants | 60 Participants | 118 Participants |
| Age Continuous | 43.0 years STANDARD_DEVIATION 9.08 | 42.3 years STANDARD_DEVIATION 9.03 | 42.7 years STANDARD_DEVIATION 9.79 |
| Region of Enrollment United States | 61 participants | 60 participants | 121 participants |
| Sex: Female, Male Female | 50 Participants | 51 Participants | 101 Participants |
| Sex: Female, Male Male | 11 Participants | 9 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 60 | 0 / 61 |
| serious Total, serious adverse events | 0 / 60 | 0 / 61 |
Outcome results
Primary
No.of Gd+ Lesions From Week 8 to Week 24
Gd+ is Gadolinium-enhancing MRI brain lesion, A marker of the opening of the blood-brain barrier and is typically used as a primary endpoints in phase II trials because of its high sensitivity to ongoing MS disease activity and its association with clinical exacerbation. The single value was calculated by summing up the lesions from week 8 to week 24.
Time frame: week 8 to week 24
Population: A total of 121 patients with relapsing forms of MS were randomized to SMT-MS or WLC. Participants were enrolled at MS specialty clinics at 3 sites in the United States (UCSF; Evergreen Hospital Medical Center, and the Feinberg School of Medicine at Northwestern University, Chicago, Illinois) and through local chapters of the National MS Society.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stress Management Therapy for Multiple Sclerosis | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 1 | 5 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 3 | 2 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 2 | 2 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ >= 4 | 5 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 0 | 46 participants |
| Wait List Control Condition | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ >= 4 | 3 participants |
| Wait List Control Condition | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 0 | 33 participants |
| Wait List Control Condition | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 1 | 13 participants |
| Wait List Control Condition | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 2 | 6 participants |
| Wait List Control Condition | No.of Gd+ Lesions From Week 8 to Week 24 | No. of Gd+ lesions(week 8 to week 24), Gd+ = 3 | 6 participants |
Comparison: It was hypothesized that treatment with stress management produced a significant reduction in cumulative Gd+ lesions compared to the control condition during the treatment periodp-value: 0.04Wilcoxon (Mann-Whitney)
Comparison: It was hypothesized that significantly greater numbers of participants receiving stress management remained free of Gd+ lesions during the treatment, compared to those receiving the control condition.p-value: 0.0295% CI: [1.17, 6.55]Logistic Regression
Secondary
No.of New or Enlarged T2 Lesions From Week 8 to Week 24
T2-weighted MRI is commonly used in phase II trials to identify more permanent lesions. The single value was calculated by summing up the lesions from week 8 to week 24.
Time frame: week 8 to week 24
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Stress Management Therapy for Multiple Sclerosis | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 1 | 8 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 3 | 1 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 2 | 1 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 >=4 | 7 participants |
| Stress Management Therapy for Multiple Sclerosis | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions (week 8 to week 24), T2 = 0 | 43 participants |
| Wait List Control Condition | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 >=4 | 10 participants |
| Wait List Control Condition | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions (week 8 to week 24), T2 = 0 | 26 participants |
| Wait List Control Condition | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 1 | 9 participants |
| Wait List Control Condition | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 2 | 9 participants |
| Wait List Control Condition | No.of New or Enlarged T2 Lesions From Week 8 to Week 24 | No. of T2 lesions(week 8 to week 24), T2 = 3 | 7 participants |
Comparison: It was hypothesized that participants receiving SMT-MS showed a significant reduction in cumulative new T2 lesions, compared to those receiving the control condition during the treatment period.p-value: 0.005Wilcoxon (Mann-Whitney)
Comparison: It was hypothesized that significantly greater numbers of participants receiving SMT-MS remained free of new T2 lesions during the treatment, compared to control condition participants.p-value: 0.00695% CI: [1.38, 6.81]Logistic Regression