Pilot Study to Assess the Efficacy of Botulinum Toxin A Treatments on Pain and Disability in Sub-Acute Low Back Pain

Pilot Study to Assess the Efficacy of Botulinum Toxin A (BOTOX®) Treatment of Paravertebral Muscles on Pain and Disability in Subjects Suffering From Sub-Acute Low Back Pain.

This study will test the hypothesis that Botulinum toxin A (BOTOX®) treatment reduces pain and disability in subjects suffering from sub-acute low back pain due to an identifiable muscle strain or back trauma occurring 6 to 16 weeks prior to enrollment. The study will also delineate the duration of medication effect and control for any placebo or mechanical trigger-point injection effect by employing a prospective, double-blind, placebo-controlled design.

Study Overview

• Status: Terminated
• Conditions: Low Back Pain
• Intervention / Treatment: Drug: Placebo; Drug: Botulinum Toxin A

Detailed Description

This study will assess the efficacy of Botulinum Toxin A (BOTOX®) injected into the lumbar paravertebral muscles for reducing pain and disability in subjects suffering from sub-acute low back pain (duration 6 to 16 weeks) arising from an identifiable muscle strain injury or back trauma. The treatment modality and techniques used are based upon three successful prior open-labeled pilot studies done by this research group investigating the effect of BOTOX® on relief of chronic low back pain. This study, however, will employ a prospective, double-blind, randomized, placebo controlled trial to control for any placebo or mechanical trigger-point injection effects. Subjects will also be assessed for 6 months to define the duration of efficacy of BOTOX®. Sixty subjects will be randomly assigned to one of two arms. There will be two parts to this study. In the first both groups will receive either BOTOX® or placebo injection into the lumbar paravertebral muscles. The subjects will be assessed using validated scales for pain and disability prior to injection and weekly to monthly thereafter for three months. Subjects who improve will have a single follow-up visit at 6 months while those subjects who do not improve will enter the second, open-label part where they will receive BOTOX® injection and be monitored weekly to monthly for the next 3 months, giving a total subject participation period of 6 months. All subjects will continue to receive any medication or physiotherapy per standard of care but those treatments will be recorded and controlled for in the data analysis.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects, 18 to 60 years of age, active duty military.
• Written informed consent and written authorization for use or release of health and research study information.
• Clear history of an identifiable muscle strain or trauma preceding the onset of low back pain.
• No prior history of vertebral disk disease/condition, sciatica or radiculopathy.
• Normal neurological examination without evidence of radiculopathy.
• History of low back pain lasting 6 to 16 weeks from the time of injury or strain.
• VAS score minimum of 5 cm at time of entry into study.
• Ability to follow study instructions and likely to complete all required visits.
• Negative urine pregnancy test prior to the administration of study medication (for females of childbearing potential) (if applicable).

Exclusion Criteria:

• Age less than 18 or greater than 60.
• Not active duty.
• Concomitant use of aminoglycoside antibiotics, curare-like agents, or other agents that might interfere with neuromuscular function.
• Any medical condition that may put the subject at increased risk with exposure to BOTOX®, including diagnosed myasthenia gravis, Eaton-Lambert syndrome, amyotrophic lateral sclerosis/motor neuron disease, neuropathy, renal stones, or any other disorder that might interfere with neuromuscular function or produce a similar type of low back pain.
• Females who are pregnant, breast-feeding, or planning a pregnancy during the study, or who think that they may be pregnant at the start of the study, or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study.
• Known allergy or sensitivity to any of the components in the study medication.
• Evidence of alcohol or substance abuse in 6 months prior to enrollment.
• Systemic medical conditions (such as thyroid disease, hypertension, bleeding disorders, diabetes, cancers, etc.) that are not currently medically managed or controlled.
• Concurrent participation in another investigational drug or device study or participation in the 30 days immediately prior to study enrollment.
• Any condition or situation that, in the investigator's opinion, may put the subject at significant risk, confound the study results, or interfere significantly with the subject's participation in the study.
• Significant Axis I or II diagnosis determined by a neurologist or psychiatrist in the 6 months prior to entry into the study.
• Duration of low back pain < 6 weeks or > 16 weeks.
• Thoracic or cervical spine pain in the absence of sub-acute low back pain.
• Anesthetic or corticosteroid injection to the lumbosacral spine within 8 weeks of enrollment.
• Spine MRI (any region) positive for acute pathology or evidence of radiculopathy on neurological examination.
• History of back surgery within one year or incomplete resolution of back pain due to a previous injury or surgery.
• Subjects involved in litigation, seeking significant disability for low back pain, or with evident secondary gain as determined by the neurologist through chart review and subject interview.
• Any previous use of BOTOX®, Dysport®, or Myobloc®.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1; Botulinum Toxin A	Drug: Botulinum Toxin A; Botulinum Toxin A; Other Names: Botox
Placebo Comparator: 2; Placebo	Drug: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Significant reduction of low back pain	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Significant reduction in long term disability	12 weeks

Collaborators and Investigators

• Sponsor: United States Department of Defense

Publications and helpful links

General Publications

• Wipf JE, Deyo RA. Low back pain. Med Clin North Am. 1995 Mar;79(2):231-46. doi: 10.1016/s0025-7125(16)30065-7.
• Frymoyer JW. Predicting disability from low back pain. Clin Orthop Relat Res. 1992 Jun;(279):101-9.
• Polo KB, Jabbari B. Effectiveness of botulinum toxin type A against painful limb myoclonus of spinal cord origin. Mov Disord. 1994 Mar;9(2):233-5. doi: 10.1002/mds.870090221.
• Rand MJ, Whaler BC. Impairment of sympathetic transmission by botulinum toxin. Nature. 1965 May 8;206(984):588-91. doi: 10.1038/206588a0. No abstract available.
• Haig AJ, LeBreck DB, Powley SG. Paraspinal mapping. Quantified needle electromyography of the paraspinal muscles in persons without low back pain. Spine (Phila Pa 1976). 1995 Mar 15;20(6):715-21.
• Foster L, Clapp L, Erickson M, Jabbari B. Botulinum toxin A and chronic low back pain: a randomized, double-blind study. Neurology. 2001 May 22;56(10):1290-3. doi: 10.1212/wnl.56.10.1290.

Study record dates

Study Major Dates

• Study Start: June 1, 2008
• Primary Completion (Anticipated): September 1, 2011
• Study Completion (Anticipated): September 1, 2011

Study Registration Dates

• First Submitted: October 4, 2006
• First Submitted That Met QC Criteria: October 4, 2006
• First Posted (Estimate): October 6, 2006

Study Record Updates

• Last Update Posted (Estimate): March 5, 2009
• Last Update Submitted That Met QC Criteria: March 4, 2009
• Last Verified: March 1, 2009

More Information

Terms related to this study

• Keywords: pain; back
• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Back Pain; Low Back Pain; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: DCI P05-71030

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No