Lumbar Stenosis Outcomes Research (LUSTOR)

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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00638443

Acronym

LUSTOR

Enrollment

Registered

2008-03-19

Start date

2008-03-31

Completion date

2010-09-30

Last updated

2016-06-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lumbar Spinal Stenosis

Keywords

Neurogenic claudication, lumbar spinal stenosis, treadmill testing

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).

Interventions

DRUGPregabalin

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.

DRUGDiphenhydramine

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.

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Time to First Symptoms of Moderate Pain	10 days	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

Measure	Time frame	Description
Total Distance	10 days	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	10 days	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	10 days	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)	10 days	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	10 days	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.
Final Pain as Measured by NRS	10 days	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.
Swiss Spinal Stenosis- Physical Function	10 days	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	10 days	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	10 days	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)	10 days	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.
Swiss Spinal Stenosis (SSS) Score- Symptom Severity	10 days	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.

Countries

United States

Participant flow

Recruitment details

Participants were recruited from the Neuromedicine Pain Treatment Center between May 2008 and February 2010

Pre-assignment details

33 participants recruited; 4 excluded (did not meet inclusion criteria based on evoked pain being less than moderate intensity during treadmill ambulation).

Participants by arm

Arm	Count
All Study Participants 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 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	29
Total	29

Withdrawals & dropouts

Period	Reason	FG000	FG001
First Intervention	Adverse Event	2	1

Baseline characteristics

Characteristic	All Study Participants
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	21 Participants
Age, Categorical Between 18 and 65 years	8 Participants
Age, Continuous	69.76 years STANDARD_DEVIATION 8.22
Region of Enrollment United States	29 participants
Sex: Female, Male Female	9 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	15 / 26	6 / 26
serious Total, serious adverse events	0 / 26	0 / 26

Outcome results

Primary

Time to First Symptoms of Moderate Pain

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.

Time frame: 10 days

Population: The analyses included all enrolled randomized subjects according to the inclusion and exclusion criteria except for the three who withdrew from the trial prior to the completion of the study. One dropped out of the study due to an adverse event (dizziness).

Arm	Measure	Value (MEAN)	Dispersion
Pregabalin	Time to First Symptoms of Moderate Pain	2.52 minutes	Standard Deviation 2.83
Diphenhydramine	Time to First Symptoms of Moderate Pain	3.06 minutes	Standard Deviation 3.11

Secondary