Lumbar Stenosis Outcomes Research (LUSTOR)
Lumbar Stenosis Outcomes Research (LUSTOR)
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.
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).
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