Study of the Insomnia in Patients With Low Back Pain

Primary Insomnia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00365976
• Other study ID #: Pro00011697
• Secondary ID: ESRC 032
• Status: Completed
• Phase: Phase 4
• First received: August 16, 2006
• Last updated: July 2, 2015
• Start date: August 2006
• Est. completion date: September 2010

Study information

• Verified date: June 2015
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: September 2010
• Est. primary completion date: September 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 64 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Back Pain
• Low Back Pain
• Primary Insomnia

Intervention

Drug:
• Eszopiclone
Eszopiclone 3 mg po nightly for duration of study blind phase.
• Placebo
Placebo nightly over duration of double blind study phase

Locations

Country	Name	City	State
United States	Duke University Medical Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Sunovion

Country where clinical trial is conducted

United States, 

References & Publications (17)

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. — View Citation

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. — View Citation

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. — View Citation

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

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

Hägg 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. — View Citation

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 (Phila Pa 1976). 2003 Apr 15;28(8):828-33. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 (Phila Pa 1976). 2004 Dec 1;29(23):E531-7. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	Mean Sleep Onset Latency (SOL)		Postnaprosyn Baseline, Week 1, Week 2 week 4	No
Secondary	Wake Time After Sleep Onset		Postnaprosyn Baseline, Week 1, Week 2 week 4	No
Secondary	Number of Awakenings		Postnaprosyn Baseline, Week 1, Week 2 week 4	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No