Lumbar Stenosis Outcomes Research II

Phase 4

Terminated

Conditions: Lumbar Spinal Stenosis

Interventions: Drug: opana then darvocet then placebo
Drug: opana then placebo then darvocet
Drug: Darvocet then opana then placebo
Drug: Placebo then darvocet then opana
Drug: Darvocet then placebo then opana
Drug: placebo then opana then darvocet

Registration Number: NCT00652093

Lead Sponsor: University of Rochester

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).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 24

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).

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Opana then darvocet then placebo	opana then darvocet then placebo	Opana IR, 5mg (oxymorphone hydrochloride) tablet was given one time at the second study visit, four days later darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the third study visit, four days later placebo tablet was given one time at the fourth study visit.
Opana then placebo then darvocet	opana then placebo then darvocet	Opana IR, 5mg (oxymorphone hydrochloride) tablet was given one time at the second study visit, four days later placebo tablet was given one time at the third study visit, four days later darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the fourth study visit.
Darvocet then opana then placebo	Darvocet then opana then placebo	Darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the second study visit, four days later Opana IR, 5mg (oxymorphone hydrochloride) tablet was given one time at the third study visit, four days later placebo tablet was given one time at the fourth study visit.
Placebo then darvocet then opana	Placebo then darvocet then opana	Placebo tablet tablet was given one time at the second study visit, four days later darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the third study visit, four days later Opana IR, 5mg (oxymorphone hydrochloride) tablet was given one time at the fourth study visit.
Darvocet then placebo then opana	Darvocet then placebo then opana	Darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the second study visit, four days later placebo tablet was given one time at the third study visit, four days later Opana IR, 5mg (oxymorphone hydrochloride) tablet was given one time at the fourth study visit.
Placebo then opana then darvocet	placebo then opana then darvocet	Placebo tablet tablet was given one time at the second study visit, four days later Opana IR, 5mg (oxymorphone hydrochloride) was given one time at the third study visit, four days later darvocet (100mg Propoxyphene/650mg Acetaminophen) tablet was given one time at the fourth study visit.

Primary Outcome Measures

Name	Time	Method
Time to First Symptoms (Tfirst) of Moderate Pain	study visit	Using the Numeric Rating Scale (NRS) (0=no pain, 10=worst pain imaginable)the time to first symptoms (Tfirst) with a NRS score greater than or equal to 4 (moderate pain level), with treadmill ambulation was measured. Patients were excluded from the trial if there pain at rest was greater than or equal to 4/10.

Secondary Outcome Measures

Name	Time	Method
Recovery Time	study visit	After the subject completed the treadmill test they were asked to immediately return to the seated position. At this point a timer was started. When the subjects pain level returned to baseline (level of pain subject felt in a seated position before walking) the time was stopped. This was recorded as recovery time. Maximum recovery time is 15 minutes.
Patient Global Assessment (PGA)	study visit	Subjects were asked to rate their low back pain according to the PGA. PGA is the impact of disease activity. PGA was measured on a 5-point scale, where 1=very good, 2=good, 3=fair, 4=poor, and 5=very poor.
Oswestry Disability Index (ODI) Score	study visit	The ODI is a set of 10 questions each with five choices (maximum score of 5 points per question) designed to determine how back pain has affected the ability to manage everyday life (pain intensity, personal care, lifting, walking, sitting, standing, sleeping, social life, traveling, and change positions). A score of 0 indicates no disability and total score of 50 would indicate 100% disability.
Final Pain	study visit	Subjects were instructed to walk on the treadmill and to tell the research coordinator to stop testing when they reached the point at which they typically would need to stop and sit down, or until 15 minutes had elapsed. At defined intervals subjects were asked what their pain level was according to the NRS. When the subject reached their maximum distance, they were asked their NRS score. This was recorded as final pain intensity.
Roland Morris Disability Questionnaire (RMDQ)	study visit	The RMDQ consists of 24 yes/no statements about activity limitations due to back pain. These questions center on movement, ambulation, and self-care activities. Positive (yes) answers each contribute 1 point to cumulative score with total scores ranging from 0 (no disability) to 24 (severely disabled).
Swiss Spinal Stenosis Score- Symptom Severity	study visit	The SSS is a series of questions asking about symptom severity, physical function, and satisfaction. The symptom severity section is a set of 7 questions (maximum score is 5 points per question) and asks to rate pain for each question based on no pain, mild, moderate, severe or very severe pain. The total score (maximum=35) is added up and divided by seven. The maximum score for the symptom severity section (score=5) indicates very severe symptom severity.
Swiss Spinal Stenosis Score- Physical Function	study visit	The SSS is a series of questions asking about symptom severity, physical function, and satisfaction. The physical function section is a series of 5 questions (maximum 4 points per question) and asks to rate function for each question based on comfortably, sometimes with pain, always with pain, no functional ability. The total score (max=20) is divided by five. The maximum score for the physical function section (max=4) indicates no ability to function.
Total Distance	study visit	Subjects were instructed to walk on the treadmill and to tell the research coordinator to stop testing when they reached the point at which they typically would need to stop and sit down, or until 15 minutes had elapsed. When the subject reached their maximum distance, the treadmill testing was stopped. This was recorded as total distance based on number of minutes and seconds walked. Minutes was converted to meters based on calculation of defined speed of the treadmill.
Area Under the Curve	study visit	Subjects were instructed to walk on the treadmill and to tell the research coordinator to stop testing when they reached the point at which they typically would need to stop and sit down, or until 15 minutes had elapsed. At defined intervals (every 30 seconds) subjects were asked what their pain level was according to the NRS. The area under the curve of present pain intensity is the total area combined for the amount of time the subject walked.
Visual Analog Scale (VAS)	study visit	The VAS asked subjects to place a mark indicative of their low back pain during the past day on a 100mm line, with 0mm representing no pain and 100mm representing extreme pain.
Modified Brief Pain Inventory (mBPI)- Interference Score	study visit	The mBPI is a series of questions that rates the severity and impact of pain on daily function. The questionnaire is made up of 4 pain severity items using the NRS scale, and seven 11-point pain interference scales (0 indicating no interference and 10 indicating complete interference). For the interference score, a total score of 10 indicates pain completely interferes with activities.