Post-laminectomy Pain Syndrome
Conditions
Keywords
post laminectomy pain syndrome, failed back surgery syndrome
Brief summary
Evaluate the analgesic benefit of Gralise® for post-laminectomy pain syndrome (PLPS)
Interventions
DRUGGralise®
14 day titration (days 1-7 at 600 mg daily Gralise®; days 8-14 at 1200 mg daily Gralise®). 28 day maintenance (1800 mg daily Gralise®). 7 day taper (days 1-4 at 1200 mg daily Gralise®; days 5-7 at 600 mg daily Gralise®).
DRUGPlacebo
14 day titration (days 1-7 at 600 mg daily placebo; days 8-14 at 1200 mg daily placebo). 28 day maintenance (1800 mg daily placebo). 7 day taper (days 1-4 at 1200 mg daily placebo; days 5-7 at 600 mg daily placebo).
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
. 1. Male and female subjects age 18 to 80 years. 2. Primary diagnosis of post-laminectomy pain syndrome (PLPS), defined as having their most severe pain related to a prior history of lumbar surgery including decompressive (e.g. laminectomy) or fusion (e.g. posterior lumbar interbody fusion) procedures performed from the L1-S1 level at least 6 months prior to enrollment. 3. Pain Detect score ≥12, denoting neuropathic pain is probable. 4. At least 50% of present pain intensity is attributed to the lower extremity (Quebec Task Force Grade 3 or 4) on most days. 5. All subjects must be decisionally capable and must give their own consent to be enrolled.
Exclusion criteria
. 1. Lumbar surgery \<6 months prior to enrollment 2. Subjects with PLPS and pain free interval (defined as chronic low back pain and radicular symptoms \<=3/10) related the indication for their PLPS defining event and a new, acute or subacute symptom pattern (e.g. new disc herniation at an adjacent level as documented by imaging). 3. Subjects regularly taking gabapentin or pregabalin for their chronic pain after spine surgery who do not endorse relief (defined as either minimally, much or very much improved on a 7 point likert scale when asked about these medications' effects). 4. Having another type of pain that is as or more severe than pain associated with PLPS. 5. An average daily pain score of 10 on the NRS scale during either the screening or initial washout period. 6. Concurrent medication that includes antiepileptic drugs (AEDs) (exceptions: pregabalin or gabapentin). 7. Subjects taking concomitant neuropathic pain medication (stable dose for at least 4 weeks) may reduce the number and/or dose of their current pain medications: If the number and/or dose exceed the limits of allowed neuropathic pain medications (refer to Use of Allowed Pain Medication), then the number and/or dose must be reduced to fall within acceptable limits. Concomitant neuropathic pain medication needs to be kept stable during the study. 8. Subjects who have previously not responded to treatment with gabapentin at doses of ≥900 mg/day or pregabalin at doses ≥300 mg/day. 9. Known hypersensitivity to Gralise, or gabapentin, or its ingredients. 10. Dose limiting adverse events to gabapentin; subjects who previously experienced dose-limiting adverse effects that prevented titration of gabapentin to an effective dose. 11. History of alcohol and/or drug abuse in the investigator's judgment, based on subject history and physical examination. 12. Subject who consumes excessive amounts of alcohol, defined as greater than 3 glasses of alcoholic beverages (1 glass is approximately equivalent to: beer \[10 ounces\], wine \[4 ounces\], or distilled spirits \[1 ounce\]) per day on a regular basis. 13. Participation in a clinical trial of an investigational drug or device within 30 days of the screening visit. 14. Gastric reduction surgery. 15. Acute gastrointestinal symptoms such as diarrhea, dyspepsia, or gastric or duodenal ulcers. 16. Malignancy within past 2 years other than basal cell carcinoma. 17. Women who are pregnant or breastfeeding. 18. History of seizure or is at risk of seizure due to head trauma. 19. History of significant cardiovascular, respiratory, endocrine, liver or kidney disease (subjects with renal impairment or creatine clearance \<30 ml/min). 20. Any significant medical condition, laboratory abnormality, or psychiatric illness (e.g. depression, mood problems, suicidal thoughts) that would prevent the subject from participating in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Numeric Rating Scale (NRS) | baseline to 6 weeks | Using the Numeric Rating Scale (NRS) (0=no pain, 10=worst pain imaginable). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Visual Analog Scale (VAS) | baseline to 6 weeks | The VAS asks 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. |
| Mean Change in Patient Global Assessment (PGA) | baseline to 6 weeks | Subjects will be asked to rate their low back pain according to the PGA. PGA is the impact of disease activity. PGA is measured on a 5-point scale, where 1=very good, 2=good, 3=fair, 4=poor, and 5=very poor. |
| Mean McGill Pain Questionnaire-2 (MPQ-2) | 6 weeks | The McGill Pain questionnaire is 22 questions where patient rate their pain symptoms with each question scaled 0-10 for a total 220 points where a higher score indicates worse outcome. |
| Mean Change in Modified Brief Pain Inventory- Short Form (mBPI-sf) | baseline to 6 weeks | 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). The scale ranges from 0 to 70. Higher scores indicate worse outcome. |
| Insomnia Severity Index (ISI) | 6 weeks | The ISI has 7 questions with each question ranging from 0-4 for a total of 28 points with higher scores indicating more severe insomnia. |
Countries
United States
Participant flow
Pre-assignment details
53 subjects signed consent and were enrolled in the study. 22 subjects were ineligible after enrollment for the following: did not meet inclusion/exclusion criteria (n=12), withdrew consent during screening period (n=5), non-responder to gabapentinoid during washout period (n=5). A total of 32 subjects were randomized, 25 completed.
Participants by arm
| Arm | Count |
|---|---|
| Group A 14 day titration (days 1-7 at 600 mg daily Gralise®; days 8-14 at 1200 mg daily Gralise®). 28 day maintenance (1800 mg daily Gralise®). 7 day taper (days 1-4 at 1200 mg daily Gralise®; days 5-7 at 600 mg daily Gralise®). 10 day washout (no intervention). 14 day titration (days 1-7 at 600 mg daily placebo; days 8-14 at 1200 mg daily placebo). 28 day maintenance (1800 mg daily placebo). 7 day taper (days 1-4 at 1200 mg daily placebo; days 5-7 at 600 mg daily placebo). | 16 |
| Group B 14 day titration (days 1-7 at 600 mg daily placebo; days 8-14 at 1200 mg daily placebo). 28 day maintenance (1800 mg daily placebo). 7 day taper (days 1-4 at 1200 mg daily placebo; days 5-7 at 600 mg daily placebo). 10 day washout (no intervention). 14 day titration (days 1-7 at 600 mg daily Gralise®; days 8-14 at 1200 mg daily Gralise®). 28 day maintenance (1800 mg daily Gralise®). 7 day taper (days 1-4 at 1200 mg daily Gralise®; days 5-7 at 600 mg daily Gralise®). | 16 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention | Adverse Event | 0 | 2 |
| First Intervention | did not receive study drug | 0 | 1 |
| First Intervention | Lost to Follow-up | 1 | 0 |
| First Intervention | Withdrawal by Subject | 1 | 0 |
| Second Intervention (Cross-over) | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 6 Participants | 9 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 10 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 15 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 14 Participants | 30 Participants |
| Region of Enrollment United States | 16 participants | 16 participants | 32 participants |
| Sex: Female, Male Female | 7 Participants | 5 Participants | 12 Participants |
| Sex: Female, Male Male | 9 Participants | 11 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 16 / 32 | 14 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
Mean Change in Numeric Rating Scale (NRS)
Using the Numeric Rating Scale (NRS) (0=no pain, 10=worst pain imaginable).
Time frame: baseline to 6 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gralise | Mean Change in Numeric Rating Scale (NRS) | -0.56 units on a scale |
| Placebo | Mean Change in Numeric Rating Scale (NRS) | -0.54 units on a scale |
Secondary
Insomnia Severity Index (ISI)
The ISI has 7 questions with each question ranging from 0-4 for a total of 28 points with higher scores indicating more severe insomnia.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gralise | Insomnia Severity Index (ISI) | 16.81 units on a scale | Standard Deviation 6.88 |
| Placebo | Insomnia Severity Index (ISI) | 18.40 units on a scale | Standard Deviation 7.34 |
Secondary
Mean Change in Modified Brief Pain Inventory- Short Form (mBPI-sf)
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). The scale ranges from 0 to 70. Higher scores indicate worse outcome.
Time frame: baseline to 6 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gralise | Mean Change in Modified Brief Pain Inventory- Short Form (mBPI-sf) | -0.07 units on a scale |
| Placebo | Mean Change in Modified Brief Pain Inventory- Short Form (mBPI-sf) | -0.07 units on a scale |
Secondary
Mean Change in Patient Global Assessment (PGA)
Subjects will be asked to rate their low back pain according to the PGA. PGA is the impact of disease activity. PGA is measured on a 5-point scale, where 1=very good, 2=good, 3=fair, 4=poor, and 5=very poor.
Time frame: baseline to 6 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gralise | Mean Change in Patient Global Assessment (PGA) | -0.04 units on a scale |
| Placebo | Mean Change in Patient Global Assessment (PGA) | -0.00 units on a scale |
Secondary
Mean Change in Visual Analog Scale (VAS)
The VAS asks 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.
Time frame: baseline to 6 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Gralise | Mean Change in Visual Analog Scale (VAS) | -0.47 mm |
| Placebo | Mean Change in Visual Analog Scale (VAS) | 0.31 mm |
Secondary
Mean McGill Pain Questionnaire-2 (MPQ-2)
The McGill Pain questionnaire is 22 questions where patient rate their pain symptoms with each question scaled 0-10 for a total 220 points where a higher score indicates worse outcome.
Time frame: 6 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Gralise | Mean McGill Pain Questionnaire-2 (MPQ-2) | 2.97 units on a scale | Standard Deviation 1.79 |
| Placebo | Mean McGill Pain Questionnaire-2 (MPQ-2) | 3.13 units on a scale | Standard Deviation 1.85 |