Clinical trial NCT00652093: Lumbar Stenosis Outcomes Research II
Official title: Lumbar Stenosis Outcomes Research II: Opana IR Versus Placebo and Active Control (Darvocet) for the Treatment of Walking Impairment in Lumbar Spinal Stenosis: A Double-Blind Randomized, Cross-Over Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Lumbar Spinal Stenosis
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: Endo Pharmaceuticals
First posted: 2008-04-03
Enrollment: 24
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 oxymorphone hydrochloride and propoxyphene/acetaminophen combination in prolonging the time to onset of pain and reducing the severity of pain associated with walking in patients lumbar spinal stenosis that have 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. The secondary objective is to examine the functional benefit of oxymorphone hydrochloride and propoxyphene/acetaminophen combination with respect to improvement in duration and distance of walking.

Detailed description: A computer-generated randomization plan was used for assignment of subjects to one of six treatment sequences (4 subjects per sequence): oxymorphone/propoxyphene/placebo, oxymorphone/placebo/propoxyphene, placebo/oxymorphone/propoxyphene, placebo/propoxyphene/oxymorphone, propoxyphene/oxymorphone/placebo, or propoxyphene/placebo/oxymorphone. One dose of blinded study drug (opana, propoxypehen, or placebo) was given at study days 1, 5, and 9. 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. Ambulation assessment was also performed 90 minutes after administration of study drug on days 1, 5 and 9, 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 (exercise 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 ≥ 6 in response to the following question: "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 a movement disorder, e.g., Parkinsonism, or an 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 or epidural steroid injection in the preceding 4 months.
* Severe psychiatric disorder
* Mean time to severe symptoms \> 15 minutes.
* Epidural steroid treatment within the last three months
* History of drug or alcohol dependence
* Serious intercurrent illness
* Hypersensitivity to oxymorphone hydrochloride
* Hypersensitivity to propoxyphene or acetaminophen
* Severe bronchial asthma or hypercarbia, morphine analogs such as codeine, or any of the other ingredients of Opana
* Suspicion of paralytic ileus
* Moderate or severe hepatic impairment
* Major conduction abnormality on ECG or cardiac (Bruce protocol) stress test within the past year.
* Ongoing treatment with a long-acting opioid or regularly-scheduled use of a short acting opioid (\>3 doses/day on four or more days/week).

Primary outcomes:
measure: Time to First Symptoms (Tfirst) of Moderate Pain
timeFrame: study visit
Secondary outcomes:
measure: Area Under the Curve
timeFrame: study visit
measure: Total Distance
timeFrame: study visit
measure: Recovery Time
timeFrame: study visit
measure: Visual Analog Scale (VAS)
timeFrame: study visit
measure: Patient Global Assessment (PGA)
timeFrame: study visit
measure: Roland Morris Disability Questionnaire (RMDQ)
timeFrame: study visit
measure: Modified Brief Pain Inventory (mBPI)- Interference Score
timeFrame: study visit
measure: Oswestry Disability Index (ODI) Score
timeFrame: study visit
measure: Swiss Spinal Stenosis Score- Symptom Severity
timeFrame: study visit
measure: Swiss Spinal Stenosis Score- Physical Function
timeFrame: study visit
measure: Final Pain
timeFrame: study visit
Other outcomes:
Locations:
city: Rochester
country: United States
facility: 2180 S. Clinton Ave
state: New York
Study officials:
affiliation: University of Rochester
name: John D Markman, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Markman JD, Gewandter JS, Frazer ME, Murray NM, Rast SA, McDermott MP, Chowdhry AK, Tomkinson EJ, Pilcher WH, Walter KA, Dworkin RH. A Randomized, Double-blind, Placebo-Controlled Crossover Trial of Oxymorphone Hydrochloride and Propoxyphene/Acetaminophen Combination for the Treatment of Neurogenic Claudication Associated With Lumbar Spinal Stenosis. Spine (Phila Pa 1976). 2015 May 15;40(10):684-91. doi: 10.1097/BRS.0000000000000837.