Study of the Insomnia in Patients With Low Back Pain

Condition(s) targeted: Primary Insomnia

Intervention: Eszopiclone (Drug); Placebo (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Duke University

Official(s) and/or principal investigator(s):
Andrew D Krystal, MD, Principal Investigator, Affiliation: Duke University

Overall contact:
Harold W Goforth, MD, Phone: 919-681-8789, Email: harold.goforth@duke.edu

The purpose of this study is to examine whether insomnia due to chronic low back pain can improve with use of eszopiclone.

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

Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Mean subjective sleep diary derived TST averaged over the entire month of the double blind phase.

Secondary outcome:

Sleep - Mean subjective SOL, WASO, Sleep Quality and Awakenings, and ISI over the month of double-blind treatment

Pain - Mean change from baseline in VAS and PGI pain ratings over the month of double blind treatment.

Function - Mean change from baseline in: RMLBPDQ, HAM-D24 rating, ISI function items, STAI ratings averaged for weeks 1,2, and 4 of double blind treatment. Change from baseline in each of the SF-36 subscales.

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.

Minimum age: 21 Years. Maximum age: 64 Years. Gender(s): Both.

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 < 6. 5 hours and/or usual SOL > 30 minutes for the last month

prior to screening;

- ISI > 14 (at least moderate insomnia);

- Age 21-64 years;

- Greater than 40 on VAS 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 NAP/LAN or ESZ;

- 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 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.

Harold W Goforth, MD, Phone: 919-681-8789, Email: harold.goforth@duke.edu

Duke University Medical Center, Durham, North Carolina 27710, United States; Recruiting
Andrew D Krystal, MD, Phone: 919-681-8789, Email: kryst001@mc.duke.edu
Harold W Goforth, MC, Phone: 919-681-8789, Email: harold.goforth@duke.edu
Andrew D Krystal, MD, Principal Investigator

Related publications:

Berry H, Bloom B, Hamilton EB, Swinson DR. Naproxen sodium, diflunisal, and placebo in the treatment of chronic back pain. Ann Rheum Dis. 1982 Apr;41(2):129-32.

Benca RM, Ancoli-Israel S, Moldofsky H. Special considerations in insomnia diagnosis and management: depressed, elderly, and chronic pain populations. J Clin Psychiatry. 2004;65 Suppl 8:26-35. Review.

Coats TL, Borenstein DG, Nangia NK, Brown MT. Effects of valdecoxib in the treatment of chronic low back pain: results of a randomized, placebo-controlled trial. Clin Ther. 2004 Aug;26(8):1249-60.

Curran MP, Wellington K. Delayed-release lansoprazole plus naproxen. Drugs. 2004;64(17):1915-9; discussion 1920-1. Review.

Edinger JD, Means MK, Stechuchak KM, Olsen MK. A pilot study of inexpensive sleep-assessment devices. Behav Sleep Med. 2004;2(1):41-9.

Hagg O, Fritzell P, Nordwall A; Swedish Lumbar Spine Study Group. The clinical importance of changes in outcome scores after treatment for chronic low back pain. Eur Spine J. 2003 Feb;12(1):12-20. Epub 2002 Oct 24.

Holm I, Friis A, Storheim K, Brox JI. Measuring self-reported functional status and pain in patients with chronic low back pain by postal questionnaires: a reliability study. Spine. 2003 Apr 15;28(8):828-33.

Katz N, Rodgers DB, Krupa D, Reicin A. Onset of pain relief with rofecoxib in chronic low back pain: results of two four-week, randomized, placebo-controlled trials. Curr Med Res Opin. 2004 May;20(5):651-8.

Koes BW, Scholten RJ, Mens JM, Bouter LM. Efficacy of non-steroidal anti-inflammatory drugs for low back pain: a systematic review of randomised clinical trials. Ann Rheum Dis. 1997 Apr;56(4):214-23. Review.

Krystal AD, Walsh JK, Laska E, Caron J, Amato DA, Wessel TC, Roth T. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep. 2003 Nov 1;26(7):793-9.

Lai KC, Lam SK, Chu KM, Hui WM, Kwok KF, Wong BC, Hu HC, Wong WM, Chan OO, Chan CK. Lansoprazole reduces ulcer relapse after eradication of Helicobacter pylori in nonsteroidal anti-inflammatory drug users--a randomized trial. Aliment Pharmacol Ther. 2003 Oct 15;18(8):829-36.

Luo X, Pietrobon R, Curtis LH, Hey LA. Prescription of nonsteroidal anti-inflammatory drugs and muscle relaxants for back pain in the United States. Spine. 2004 Dec 1;29(23):E531-7.

Ostelo RW, de Vet HC. Clinically important outcomes in low back pain. Best Pract Res Clin Rheumatol. 2005 Aug;19(4):593-607. Review.

Pallay RM, Seger W, Adler JL, Ettlinger RE, Quaidoo EA, Lipetz R, O'Brien K, Mucciola L, Skalky CS, Petruschke RA, Bohidar NR, Geba GP. Etoricoxib reduced pain and disability and improved quality of life in patients with chronic low back pain: a 3 month, randomized, controlled trial. Scand J Rheumatol. 2004;33(4):257-66.

Rives PA, Douglass AB. Evaluation and treatment of low back pain in family practice. J Am Board Fam Pract. 2004 Nov-Dec;17 Suppl:S23-31.

Smith MT, Haythornthwaite JA. How do sleep disturbance and chronic pain inter-relate? Insights from the longitudinal and cognitive-behavioral clinical trials literature. Sleep Med Rev. 2004 Apr;8(2):119-32. Review.

Zammit GK, McNabb LJ, Caron J, Amato DA, Roth T. Efficacy and safety of eszopiclone across 6-weeks of treatment for primary insomnia. Curr Med Res Opin. 2004 Dec;20(12):1979-91.

Starting date: August 2006
Ending date: September 2009
Last updated: January 9, 2008