Study of the Insomnia in Patients With Low Back Pain

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to examine whether insomnia due to chronic low back pain can improve with use of eszopiclone.

Detailed Description
-----------------
There is a great need to develop effective treatments for insomnia in patients with chronic low-back pain. Chronic low-back pain is among the most prevalent of all health complaints, is associated with enormous health-care and productivity costs, reduced quality of life, and limitation of function and is almost universally associated with insomnia (Rives and Douglas, 2004). While it had long been believed that insomnia was a symptom of pain conditions and of little consequence in its' own right, a growing literature suggests that insomnia has important effects on the clinical course of pain syndromes (Smith and Haythornthwaite, 2004). While pain may disrupt sleep, it appears that problems with sleep increase pain and are associated with impairments in daytime function. The emerging point of view is that specific treatment for both pain and insomnia is needed for optimal clinical management (Smith and Haythornthwaite, 2004). Surprisingly, despite the fact that chronic low-back pain is the most common pain condition, the treatment of insomnia in this disease has never been studied. As a result, we propose to carry out the first double-blind placebo-controlled study of the treatment insomnia in patients with chronic low back pain. Comparison(s): We will test the hypothesis that treating the insomnia with eszopiclone 3 mg (ESZ) along with management of pain with naproxen 500 mg bid (NAP) will result in statistically significantly improved sleep compared with placebo. We also propose to test as a secondary hypothesis that treatment with ESZ will lead to significant improvement in pain and daytime function vs. placebo.

Official Title
-----------------
Double-blind, Placebo-controlled Study of the Safety and Efficacy of Eszopiclone in the Treatment of Insomnia in Patients With Chronic Low Back Pain

Conditions
-----------------
Primary Insomnia

Intervention / Treatment
-----------------
* Drug: Eszopiclone
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: • Diagnosis of insomnia based on DSM-IV criteria for insomnia due to a general medical condition (low-back pain); The insomnia must not predate the onset of low-back pain by more than 1 month; Usual nightly TST (Total Sleep Time) < 6.5 hours and/or usual SOL (Sleep Onset Latency) > 30 minutes for the last month prior to screening; ISI (Insomnia Severity Index) > 14 (at least moderate insomnia); Age 21-64 years; Greater than 40 on VAS (Visual Analog Scale) for pain (scale is 0-no pain to 100-worst imaginable pain); Patient Global Impression of Pain of at least 3 (on a 1-5 scale, indicating at least moderate severity); reported Back pain must be greater than reported leg pain, and there must be no signs of spinal nerve root compression; presence of normal motor strength on exam; duration of chronic low back pain of greater than three months; low back pain location must be inferior to T12 and superior to the gluteal fold. Exclusion Criteria: • Significant medical or neurological illness in excess of that which is directly responsible for the chronic low back pain; the presence of an active and significant psychiatric disease with a substantive impact on sleep; meeting DSM-IV criteria for an Axis I disorder within the last three months, or meeting criteria for substance abuse within the last 12 months; current pregnancy; history of hypersensitivity, intolerance, or contraindication to Naproxen/Lansoprazole or Eszopiclone; baseline creatinine of 2.0 or greater; patient taking other medications having significant renal effects (e.g. lithium, ACE inhibitor, angiotensin receptor antagonist, or thiazide/loop diuretics); patients taking other anticoagulants; patients having an allergy to aspirin; history of diagnosed gastric or duodenal ulcer; history of bleeding or clotting diathesis; lifetime history of myocardial infarction or cerebrovascular accident; Elevated PT/PTT/INR (Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio)at screening; Abnormal kidney function detected in screening labs; history of back related surgery within the past 3 months; history of corticosteroid use in the past 30 days; presence of currently pending litigation or worker's compensation claim related to the chronic low back pain; inability to follow study procedures or complete the study; or the use of any medications that could affect sleep within 5 half-lives of screening; history of back surgery within the past 2 years with the exception of a discectomy; pregnant or lactating females; women of child-bearing potential who will not agree to use approved means of birth control during the trial; history of any surgery within the past one month; history of any major physical trauma within the last 6 months; history of corticosteroid use within the last 90 days; diagnosis of rheumatoid or psoriatic arthritis; history of fibromyalgia; presence of spondyloarthropathy; presence of sciatica; spinal stenosis; presence of any vertebral fractures, spondylolisthesis; or radicular back pain.

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 64 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Placebo | Drug: Placebo<br>* Placebo nightly over duration of double blind study phase<br>|
| Active Comparator: 2<br>Eszopiclone | Drug: Eszopiclone<br>* Eszopiclone 3 mg po nightly for duration of study blind phase.<br>* Other names: Lunesta;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Subjective Sleep Diary Derived Total Sleep Time (TST) | Nightly total sleep time was averaged from diary entries. | Postnaprosyn baseline, Week 1, week 2, week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Analog Scale Pain Ratings (VAS) | Scores are measured on a 100 mm Visual Analog Scale (VAS). The VAS scale ranges from 0 to 100 mm with the lower score indicating less pain and the higher score indicating greater pain | Postnaprosyn baseline, Week 1, Week 2, Week 4 | 
| Mean Sleep Onset Latency (SOL) |  | Postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Wake Time After Sleep Onset |  | Postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Number of Awakenings |  | Postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Sleep Quality Ratings | Sleep quality ratings are based on a 1-10 Likert scale. Low scores represent poorer sleep quality and higher scores represent better quality sleep | Postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Insomnia Severity Index (ISI) | The ISI is a seven-item self-report questionnaire that provides a global measure of insomnia severity based on difficulty falling or staying asleep, satisfaction with sleep, or degree of impairment with daytime functioning. The total score ranges from 0-28: 0-7 (no clinical insomnia), 8-14 (subthreshold insomnia), 15-21 (insomnia of moderate severity), and 22-28 (severe insomnia). | Prenaprosyn Baseline, Postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Patient Global Impression of Pain Ratings | Pain ratings included a global impression of pain rating (PGI) (1-5 rating with 1 being little pain and 5 is worst pain) | postnaprosyn Baseline, Week 1, Week 2 week 4 | 
| Roland Morris Low Back Pain Inventory (RMLBPI) | The Roland-Morris Low Back Pain Disability Questionnaire (RMLBPDQ) is a 24-item instrument that assesses the extent to which activities of daily living are affected by LBP. It is composed of 24 yes-no items assessing potential disabilities. Scores range from 0 (no disability) to 24 (severe disability). | prenaprosyn baseline, postnaprosyn Baseline, Week 1, Week 2, week 4 | 
| Hamilton Depression Rating Scale (HAM-D-24) | The Hamilton Depression Scale - 24 Items (HAM-D-24) measures depression severity. Items are rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score range of 0 to 76. The higher the score, the more severe. | prenaprosyn baseline, postnaprosyn Baseline, Week 1, Week 2, week 4 | 
| Short Form 36 Health Survey Questionnaire (SF-36) | The SF-36 is a participant self-rated questionnaire that is a general measure of perceived health status comprising 36 questions, which yields an 8-scale health profile. The vitality sub-score assesses energy and fatigue, and ranges from 0 (worst) - 100 (best). | Baseline, week 1, week 2, week 4 | 
| State-Trait Anxiety Inventory (STAI) | Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 40-160, where a lower value shows a larger improvement) | Baseline, week 1, week 2, week 4 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Insomnia, Low Back Pain, Hypnotics, Eszopiclone, Pain, Disability