Study of the Insomnia in Patients With Low Back Pain

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.

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.