Lumbar Stenosis Outcomes Research (LUSTOR) (LUSTOR)

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by (Responsible Party):
John Markman, University of Rochester
ClinicalTrials.gov Identifier:
NCT00638443
First received: March 12, 2008
Last updated: May 11, 2016
Last verified: May 2016
  Purpose
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.

Condition Intervention Phase
Lumbar Spinal Stenosis
Drug: Pregabalin
Drug: Diphenhydramine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • Time to First Symptoms of Moderate Pain [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Final Pain as Measured by NRS [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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. 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.

  • Total Distance [ Time Frame: 10 days ] [ Designated as safety issue: Yes ]
    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.

  • Recovery Time [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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.

  • Area Under the Curve [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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 multiplied by the amount of time the subject walked.

  • Visual Analog Scale (VAS) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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.

  • Oswestry Disability Index (ODI) Score [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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 total score range of 0-50; score of 0 indicates no disability and a score of 50 would indicate 100% disability.

  • Swiss Spinal Stenosis (SSS) Score- Symptom Severity [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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- Physical Function [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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.

  • Modified Brief Pain Inventory (mBPI)- Interference Score [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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 pain interference sub-scales. The final interference score is an average of the seven sub-scales (0 indicating no interference and 10 indicating complete interference).

  • Roland Morris Disability Questionnaire [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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).

  • Patient Global Assessment (PGA) [ Time Frame: 10 days ] [ Designated as safety issue: No ]
    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.


Enrollment: 29
Study Start Date: March 2008
Study Completion Date: September 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Pregabalin then Diphenhydramine
Pregabalin started at 75mg twice daily for 3 days; pregabalin increased to 150mg twice daily for 7 days; pregabalin reduced to 75mg twice daily for 3 days; no drug for 7 days; diphenhydramine started at 6.25mg twice daily for 3 days; diphenhydramine increased to 12.5mg twice daily for 7 days; diphenhydramine reduced to 6.25mg twice daily for 3 days.
Drug: Pregabalin
Pregabalin started at 75mg twice daily for 3 days; pregabalin increased to 150mg twice daily for 7 days; pregabalin reduced to 75mg twice daily for 3 days.
Other Name: Lyrica
Drug: Diphenhydramine
diphenhydramine started at 6.25mg twice daily for 3 days; diphenhydramine increased to 12.5mg twice daily for 7 days; diphenhydramine reduced to 6.25mg twice daily for 3 days.
Other Name: Benedryl
Diphenhydramine then Pregabalin
diphenhydramine started at 6.25mg twice daily for 3 days; diphenhydramine increased to 12.5mg twice daily for 7 days; diphenhydramine reduced to 6.25mg twice daily for 3 days; no drug for 7 days; pregabalin started at 75mg twice daily for 3 days; pregabalin increased to 150mg twice daily for 7 days; pregabalin reduced to 75mg twice daily for 3 days.
Drug: Pregabalin
Pregabalin started at 75mg twice daily for 3 days; pregabalin increased to 150mg twice daily for 7 days; pregabalin reduced to 75mg twice daily for 3 days.
Other Name: Lyrica
Drug: Diphenhydramine
diphenhydramine started at 6.25mg twice daily for 3 days; diphenhydramine increased to 12.5mg twice daily for 7 days; diphenhydramine reduced to 6.25mg twice daily for 3 days.
Other Name: Benedryl

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

Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00638443

Locations
United States, New York
2180 South Clinton Avenue
Rochester, New York, United States, 14618
Sponsors and Collaborators
University of Rochester
Pfizer
Investigators
Principal Investigator: John D Markman, M.D University of Rochester
  More Information

Publications:
Responsible Party: John Markman, Director, Translational Pain Research, University of Rochester
ClinicalTrials.gov Identifier: NCT00638443     History of Changes
Other Study ID Numbers: 16697  IIR#GA00818X 
Study First Received: March 12, 2008
Results First Received: July 9, 2012
Last Updated: May 11, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Rochester:
Neurogenic claudication, lumbar spinal stenosis, treadmill testing

Additional relevant MeSH terms:
Constriction, Pathologic
Spinal Stenosis
Pathological Conditions, Anatomical
Spinal Diseases
Bone Diseases
Musculoskeletal Diseases
Pregabalin
Diphenhydramine
Promethazine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anticonvulsants
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anesthetics, Local
Anesthetics
Antiemetics
Autonomic Agents
Gastrointestinal Agents
Histamine H1 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents

ClinicalTrials.gov processed this record on July 28, 2016