Clinical trial NCT03949296: Mindfulness Meditation in Treating Insomnia in Multiple Sclerosis
Official title: A Randomized, Placebo-Controlled Study of Mindfulness Meditation in Treating Insomnia in Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insomnia Chronic
Multiple Sclerosis
Lead sponsor: Griffin Hospital
Sponsor class: OTHER
Collaborators: name: Yale-Griffin Prevention Research Center
name: Yale University- Stress Center
First posted: 2019-05-14
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A placebo-controlled, randomized, single-blinded clinical study involving a projected 90 participants with multiple sclerosis in a 50:50 randomization scheme.
Primary purpose: PREVENTION

Brief summary: Purpose To determine whether Mindfulness-Based Treatment for Insomnia (MBTI) is more effective in the treatment of chronic insomnia disorder (CID) in patients with multiple sclerosis (MS) when compared with standard sleep hygiene counseling.

Specific Aims / Hypotheses

Our specific aims are to determine:

* Whether MBTI is more effective than standard sleep hygiene counseling in improving objectively-measured sleep quality among this group of MS patients with CID, as measured by the Fitbit Charge 2 activity tracker.
* Whether MBTI is more effective than standard sleep hygiene counseling in improving self-reported sleep quality among this group of MS patients with CID, as measured by the Pittsburgh Sleep Quality Index (PSQI).
* Whether MTBI is more effective than standard sleep hygiene counseling in reducing self-reported severity of insomnia among this group of MS patients with CID, as measured by the Insomnia Severity Index (ISI).
* Whether MBTI is more effective than standard sleep hygiene counseling in improving self-reported quality of life among this group of MS patients with CID, as measured by the Multiple Sclerosis Quality of Life Inventory (MSQLI).

We hypothesize that among study participants with MS and CID:

* MBTI will improve their objectively-measured sleep quality, as measured by the Fitbit Charge 2 activity tracker.
* MBTI will improve their self-reported sleep quality, as measured by the PSQI.
* MBTI will reduce their self-reported severity of insomnia, as measured by the ISI.
* Improvement in sleep quality and reduction in insomnia severity will result in improvement in self-reported quality of life, as measured by MSQLI scores.
* MBTI will be superior to sleep hygiene counseling in improving sleep quality, reducing insomnia severity, and improving quality of life.

Detailed description: BACKGROUND:

An estimated 25 to 40 percent of individuals with multiple sclerosis (MS) suffer from chronic insomnia, and the prevalence of sleep disorders is often unrecognized. Chronic insomnia disorder (CID) is defined as persistent difficulty with sleep initiation, duration, consolidation, or quality that occurs despite adequate opportunity and circumstances for sleep, leading to daytime impairment, and ongoing for at least three consecutive months.

Common causes of CID in MS include motor disorders such as cramps, spasms, restless leg syndrome and periodic limb movements, neuropathic pain, bladder dysfunction (such as nocturia), and obstructive sleep apnea. Depression, anxiety, daytime fatigue, and cognitive dysfunction are also associated with sleep disorders in MS. Moreover, treatments for the underlying disease, such as interferon therapy, as well as treatments for various symptoms of MS, such as stimulant medications used to treat fatigue, may also contribute to insomnia.

Many patients manage their insomnia using benzodiazepines and other medications, which may be associated with a number of adverse effects, including dependence and tolerance, cognitive dysfunction, and depression. Furthermore, other adverse effects of benzodiazepines arise from their use in combination with other drugs such as opioid narcotics for pain. Therefore, it is desirable to find effective nonpharmacological treatments for insomnia in patients with multiple sclerosis.

Psychologically-based and behavioral treatments have been widely tested in various cohorts of patients with CID with and without co-morbid conditions. These methods include cognitive behavioral therapies (CBT), sleep hygiene programs, mindfulness meditation, and others. In a randomized controlled clinical trial of 72 women with CID and MS in Iran, CBT treatment was associated with improved sleep quality as measured by the Pittsburgh Sleep Quality Index (PSQI). A case series of 11 patients with chronic insomnia and MS who were treated with CBT at the Cleveland Clinic Sleep Disorders Center improved on measures of insomnia, fatigue and depression, as well as an increase in total sleep time of 1.5 hours.

Mindfulness based stress reduction (MBSR) is an empirically-supported intervention designed to decrease stress, chronic and acute pain and anxiety in adults. Mindfulness is the practice of focusing full attention on the present moment intentionally and without judgment. The practice of mindfulness is hypothesized to reduce feelings of distress and stress reactivity by increasing one's awareness of and ability to tolerate thoughts and emotions. Mindfulness may help individuals decrease distress and over-reactivity to events and increase the ability to respond to events in ways that one consciously chooses (rather than through automatic 'mindless" behaviors). Mindfulness-based interventions such as MBSR teach mindfulness through meditation, yoga, present-minded awareness in everyday life, and discussions of stress physiology and coping.

Several studies have demonstrated the effectiveness of MBSR interventions in the treatment of insomnia. Long-term meditators have been shown to have increased parietal-occipital gamma (25-40 Hz) during NREM (non-rapid eye movement sleep), showing that MBSR can induce objective changes in sleep architecture. MBSR and MBTI (mindfulness based treatment of insomnia) have been shown in randomized, controlled studies to decrease sleep latency and total waking time and increase sleep time.These effects, moreover, have been durable. However, a meta-analysis of 6 randomized controlled trials involving 330 participants showed that mindfulness meditation significantly improved total wake time and sleep quality, but had no significant effects on sleep onset latency, total sleep time, wake after sleep onset, sleep efficiency, total wake time, Insomnia Severity Index (ISI), PSQI, or Dysfunctional Beliefs and Attitudes Sleep Scale (DBAS).

Mindfulness training has been shown to be beneficial in improving several symptoms of MS, including those that have been shown to impact sleep. A randomized, controlled study of 150 patients undergoing mindfulness training showed improvements in quality of life and well-being, including fatigue and depression. Furthermore, there is Class 1 evidence that stress reduction in MS can affect the underlying inflammatory biology of MS, as evidenced by a reduction in new MRI lesions. However, many other studies showing benefits of stress reduction in MS are limited by their descriptive nature and non-controlled design.

The significance of this study is that while there are data showing the effectiveness of mindfulness-based techniques in treating insomnia in general, and some data showing the benefits of using non-mindfulness stress reduction techniques in the management of MS-related insomnia, there have been no studies to date on the efficacy of mindfulness techniques in treating MS-related insomnia.

Eligibility criteria: Inclusion Criteria:

1. Men and women age 18 years or older
2. Diagnosis of multiple sclerosis per the 2014 Revised MacDonald criteria
3. Moderate to severe insomnia based on Insomnia Severity Index score
4. Kurtzke Expanded Disability Status Scale (EDSS) score between 0 and 7.0
5. Stable medications and disease activity for the past 30 days
6. Willingness to visit Griffin Hospital for up to 13 times if assigned to the mindfulness group, or up to 4 times if assigned to the sleep hygiene group, for study assessment and counseling or educational sessions

Exclusion Criteria:

1. Diagnosis of obstructive sleep apnea or narcolepsy
2. High risk of obstructive sleep apnea, as determined by the STOP-Bang questionnaire, if no known diagnosis of sleep apnea
3. Significant pulmonary, cardiac, hepatic or other medical conditions
4. Relapse of MS symptoms within the 30 days prior to study entry
5. Use of corticosteroids, either IV or oral, for exacerbations of symptoms
6. Inability to comply with the protocol
7. A lack of proficiency in reading, writing in, and understanding English
8. Body mass index (BMI) \> 39 (350 lb. due to the limitations of the scale used for the study)

Primary outcomes:
measure: Sleep Quality
timeFrame: 4 months
Secondary outcomes:
measure: Self-Reported Sleep Quality
timeFrame: 4 months
measure: Self-Reported Quality of Life
timeFrame: 4 months
Other outcomes:
measure: Adverse Events
timeFrame: 4 months
measure: Progression of MS
timeFrame: 4 months
measure: Muscle Spasticity
timeFrame: 4 months
measure: Restless Leg
timeFrame: 4 months
measure: Medication and Supplements
timeFrame: 4 months
Locations:
city: Derby
country: United States
facility: Yale-Griffin Prevention Research Center
state: Connecticut
Study officials:
affiliation: Griffin Hospital
name: Joseph B Guarnaccia, MD
role: PRINCIPAL_INVESTIGATOR
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