Clinical trial NCT00638443: Lumbar Stenosis Outcomes Research (LUSTOR)
Official title: Lumbar Stenosis Outcomes Research (LUSTOR)- A Randomized, Double-blind, Cross-over Trial of Pregabalin vs. Diphenhydramine in Patients With Lumbar Spinal Stenosis and Neuropathic Low Back Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Lumbar Spinal Stenosis
Keywords: Neurogenic claudication, lumbar spinal stenosis, treadmill testing
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2008-03-19
Enrollment: 29
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The primary objective of the proposed pilot study is to determine the efficacy of pregabalin in prolonging the time to onset of pain and reducing the severity of pain associated with walking in patients with neurogenic claudication. Neurogenic claudication is defined as movement induced leg pain, numbness, heaviness, or vague discomfort in part or all of one or both legs provoked with walking and standing and relieved by sitting, squatting, or forward flexion posturing. The secondary objective is to examine the functional benefit of pregabalin with respect to improvement in duration and distance of walking.

Detailed description: Subjects were randomized into one of two treatment sequences: pregabalin/active placebo or active placebo/pregabalin. Each arm lasted 10 days, with a washout period of 10 days between treatments. Pregabalin was administered as a standardized two step titration, starting at 75mg twice daily up to a maximum daily dose of 150mg twice daily; and likewise, diphenhydramine (active placebo) was administered starting at 6.25mg twice daily up to a maximum daily dose of 12.5mg twice daily. The primary endpoint was time to first symptoms of moderate intensity (NRS ≥ 4/10) during treadmill ambulation. Ambulation assessment was performed during the screening visit, and on day 10 of each period to evaluate pain intensity associated with walking as well as distance covered by the patients. Quantitative assessment of ambulation was conducted on a treadmill at 0° ramp incline at 1.2 miles per hour (mph). Measurement of self-reported symptom severity using the NRS at baseline, and every 30 seconds for a maximum of 15 minutes was recorded. The following information was also recorded: time to first symptoms, total ambulation time. The examination was stopped after 15 minutes or at the onset of severe symptoms. Severe symptoms were defined as the level of discomfort that would make patients stop walking in usual life situations. No one was encouraged or prompted to continue walking beyond this point. Patients were instructed to walk with an upright posture. They were not permitted to lean forward or hold onto the handrails during the examination. Secondary outcome measures included area under the curve of present pain intensity with ambulation at each specified time point, final pain intensity with walking, walking tolerance, time to return to baseline pain level after ambulation, as well as the results of a series of pain related questionnaires including: Visual Analog Scale (VAS), Patient Global Assessment (PGA), NRS, Roland Morris Disability Questionnaire (RMDQ), modified Brief Pain Inventory short form (mBPI-sf), Oswestry Disability Index (ODI), and Swiss Spinal Stenosis (SSS).

Eligibility criteria: Inclusion Criteria:

* Patients must present with clinical symptoms of neurogenic claudication (neurogenic claudication is defined as movement induced leg pain, numbness, heaviness, or vague discomfort in part or all of one or both legs provoked with walking and standing and relieved by sitting, squatting, or forward flexion posturing) and endorse limitation of walking tolerance due to these symptoms
* Numeric Rating Scale (NRS) for pain greater than or equal to 6 in response to the following questions: "Circle one number (from 0=no pain to 10=worst pain)-How would you rate the worst leg and lower back pain you experienced during walking last week?"
* Patients must have confirmatory imaging by MRI or CT scan demonstrating at least one level of lumbar spinal stenosis within 1 year
* Duration of symptoms \> 3 months
* Age \> 50 years; male or female

Exclusion Criteria:

* Past or present existence of movement disorder, e.g., Parkinsonism,or a neurologic disease that might affect the ability to ambulate (e.g., signs/symptoms of cauda equina compression)
* Cognitive impairment preventing full understanding or participation in the study
* Peripheral vascular disease
* Moderate to severe arthritis of the knee or hip that might severely compromise ambulation
* Past or present lower extremity peripheral vascular disease
* Serious concomitant medical illness (e.g., heart disease) that might impair ambulation assessment
* Previous lumbar surgery for spinal stenosis (laminectomy with or without fusion) within the past 2 years
* Prior treatment with study drug for neurogenic claudication
* Severe psychiatric disorder
* Mean time to severe symptoms \> 15 minutes.
* Epidural steroid treatment within the last three months
* Ongoing treatment with gabapentin
* Hypersensitivity or allergic reaction to diphenhydramine

Primary outcomes:
measure: Time to First Symptoms of Moderate Pain
timeFrame: 10 days
Secondary outcomes:
measure: Final Pain as Measured by NRS
timeFrame: 10 days
measure: Total Distance
timeFrame: 10 days
measure: Recovery Time
timeFrame: 10 days
measure: Area Under the Curve
timeFrame: 10 days
measure: Visual Analog Scale (VAS)
timeFrame: 10 days
measure: Oswestry Disability Index (ODI) Score
timeFrame: 10 days
measure: Swiss Spinal Stenosis (SSS) Score- Symptom Severity
timeFrame: 10 days
measure: Swiss Spinal Stenosis- Physical Function
timeFrame: 10 days
measure: Modified Brief Pain Inventory (mBPI)- Interference Score
timeFrame: 10 days
measure: Roland Morris Disability Questionnaire
timeFrame: 10 days
measure: Patient Global Assessment (PGA)
timeFrame: 10 days
Other outcomes:
Locations:
city: Rochester
country: United States
facility: 2180 South Clinton Avenue
state: New York
Study officials:
affiliation: University of Rochester
name: John D Markman, M.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Simon LS, Evans C, Katz N, Bombardier C, West C, Robbins J, Copley-Merriman C, Markman J, Coombs JH. Preliminary development of a responder index for chronic low back pain. J Rheumatol. 2007 Jun;34(6):1386-91.
citation: Markman JD, Dworkin RH. Ion channel targets and treatment efficacy in neuropathic pain. J Pain. 2006 Jan;7(1 Suppl 1):S38-47. doi: 10.1016/j.jpain.2005.09.008.
citation: Deen HG Jr, Zimmerman RS, Lyons MK, McPhee MC, Verheijde JL, Lemens SM. Test-retest reproducibility of the exercise treadmill examination in lumbar spinal stenosis. Mayo Clin Proc. 2000 Oct;75(10):1002-7. doi: 10.4065/75.10.1002.
citation: Deen HG, Zimmerman RS, Lyons MK, McPhee MC, Verheijde JL, Lemens SM. Use of the exercise treadmill to measure baseline functional status and surgical outcome in patients with severe lumbar spinal stenosis. Spine (Phila Pa 1976). 1998 Jan 15;23(2):244-8. doi: 10.1097/00007632-199801150-00019.
citation: Stucki G, Daltroy L, Liang MH, Lipson SJ, Fossel AH, Katz JN. Measurement properties of a self-administered outcome measure in lumbar spinal stenosis. Spine (Phila Pa 1976). 1996 Apr 1;21(7):796-803. doi: 10.1097/00007632-199604010-00004.