Neuropathy, Pain
Conditions
Keywords
chemotherapy
Brief summary
The investigators seek to investigate certain patient characteristics that would predict the response to a currently approved analgesic, pregabalin, in patients with chronic pain due to nerve damage caused by chemotherapy. Patients with this painful condition, called chemotherapy-induced peripheral neuropathy (CIPN) have a current or recent history of chemotherapy with particular chemotherapy agents called taxanes or oxaliplatin. The investigators will recruit potential subjects from both the Siteman Cancer Center and the Washington University Pain Management Center. Those patients who meet the inclusion and satisfy the exclusion criteria will be enrolled. Subjects will undergo mechanical and thermal sensitivity testing on their extremities, will provide quality of life information by completing questionnaires and will receive pregabalin followed by placebo, or placebo followed by pregabalin \[crossover design\] in order to assess how well the sensory tests predict the analgesic effect of pregabalin (compared to placebo).
Interventions
DRUGPregabalin
Anticonvulsant
DRUGPlacebo
Identical, matching inactive substance
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age \>18 2. Distal symmetric pain distribution (both feet, with or without pain in hands). 3. The pain appeared during or up to 12 weeks after treatment with oxaliplatin, paclitaxel, docetaxel or any combination of these. 4. Score of 4 or more on DN4 (Douleur Neuropathique 4) neuropathic pain questionnaire 5. Pain duration \> 2 months. 6. Patient report of average daily pain intensity in the last week \>3 on 0-10 Numerical Rating Scale (NRS). 7. Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. 8. Able and willing to sign an IRB-approved written informed consent.
Exclusion criteria
1. Hypersensitivity to pregabalin. 2. Current treatment with pregabalin. 3. Current treatment with a vinca alkaloid (e.g. vincristine, vinblastine), or CIPN that may be associated with previous treatment with a vinca alkaloid. 4. History of diabetes mellitus or a neurological disorder with any previous signs of distal symmetric polyneuropathy. 5. Moderate to severe renal failure (Creatinine clearance \< 30mL/min, by Cockcroft-Gault formula). 6. ALT (alanine aminotransferase) or AST (aspartate aminotransferase ) \> 3 times the upper limit of normal. 7. Planned surgeries or radiation treatment within 10 weeks following study inclusion. 8. Inability to complete pain self-report. 9. Pregnancy or lactation 10. Patients with seizure disorders treated with anticonvulsants 11. Current participation in a trial with another investigational agent. 12. Concomitant medication as follows: * Subjects treated with gabapentin or other anticonvulsant for neuropathic pain will be required to taper the medication and discontinue for at least 2 weeks prior to study initiation. * Patients on antidepressant treatment for pain or depression (TCAs, SSRI, SNRIs etc. will be allowed to continue their medications provided they have been on a stable dose for at least 4 weeks before study initiation. No dose regimen changes of antidepressants will be allowed during the study period. * Patients on around-the clock opioid treatment (including tramadol) will be allowed to continue their medication provided they have been on a stable dose for at least 4 weeks before study initiation. The maximum allowed dose of opioid will be equivalent to 60mg oral morphine sulphate. Patients with higher doses will be required to taper down their opioid dose to maximum 60mg oral morphine equivalent, and continue on stable dose for 4 weeks before enrollment in the study. Short-acting opioids for painful CIPN treatment will not be allowed. * Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) will be discontinued at least 2 weeks before study initiation. However, low-dose aspirin (≤325mg/day) will be allowed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Spontaneous Pain Intensity as a Function of Baseline MPT | Baseline to week 4 | Correlation between Mechanical Pain Threshold (MPT in mN) at baseline and reduction in spontaneous pain intensity (% reduction on 0-10 NRS) at the end of 4-week treatment. The slopes (Pearson coefficients) of the correlation obtained from pregabalin vs. placebo will be compared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in NPSI Outcomes | Baseline to week 4 | Change from baseline to week 4 in total NPSI (Neuropathic Pain Symptom Inventory) score The total NPSI score is comprised by adding 5 sub-scores (Burning pain, Pressing pain, Paroxysmal pain, Evoked pain, and Paresthesia/Dysesthesia) and is expressed on a 0-100 scale; 0-minimum (least), and 100 maximum (worst) score |
| Change in BPI Outcomes (SEVERITY) | Baseline to week 4 | Change from baseline to week 4 in BPI (Brief Pain Inventory) pain severity severity score BPI severity score is expressed on 0-10 scale, with 0 being the minimum (least), and 10 being the maximum (worst) pain severity |
| Absolute Change in Pain Intensity, Measured on 0-10 Numerical Rating Scale (NRS) | Baseline to week 4 | Absolute change in pain intensity on 0-10 numerical rating scale (NRS) from baseline to 4 weeks with pregabalin vs. placebo NRS: 0= no pain, 10= worst pain |
| Change in BPI Outcomes (INTERFERENCE) | baseline to week 4 | Change from baseline to week 4 in BPI (Brief Pain Inventory) pain interference score BPI interference score is expressed on 0-10 scale, with 0 being the minimum (least), and 10 being the maximum (worst) pain interference |
| Number of Patients With Significant Pain Reduction | Baseline to week 4 | Number of patients who experienced 50% or more reduction in average daily pain (on 0-10 NRS, Numerical Rating Scale, where 0=least pain, 10=worst pain) |
| Change in Sleep Problem Index (SPI) Outcomes | Baseline to week 4 | Change from baseline to week 4 in SPI (Sleep Problem Index) score, on 0-100 scale, where 0= best (least) score, and 100= maximum (worst) score |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pregabalin First Then Placebo Pregabalin administered for 4 weeks, titrated to highest tolerated dose up to 600 mg/day.
Pregabalin: Anticonvulsant
Placebo: Identical, matching inactive substance | 12 |
| Placebo First Then Pregabalin Identical, matching inactive substance administered for 4 weeks following the same dosing regimen.
Pregabalin: Anticonvulsant
Placebo: Identical, matching inactive substance | 14 |
| Total | 26 |
Baseline characteristics
| Characteristic | Pregabalin First Then Placebo | Total | Placebo First Then Pregabalin |
|---|---|---|---|
| Age, Continuous | 65.1 years STANDARD_DEVIATION 8.2 | 62.3 years STANDARD_DEVIATION 10.2 | 59.9 years STANDARD_DEVIATION 11.4 |
| 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 | 2 Participants | 2 Participants | 0 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 | 10 Participants | 24 Participants | 14 Participants |
| Region of Enrollment United States | 12 participants | 26 participants | 14 participants |
| Sex: Female, Male Female | 5 Participants | 8 Participants | 3 Participants |
| Sex: Female, Male Male | 7 Participants | 18 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 23 / 25 | 21 / 25 |
| serious Total, serious adverse events | 1 / 25 | 0 / 25 |
Outcome results
Primary
Change in Spontaneous Pain Intensity as a Function of Baseline MPT
Correlation between Mechanical Pain Threshold (MPT in mN) at baseline and reduction in spontaneous pain intensity (% reduction on 0-10 NRS) at the end of 4-week treatment. The slopes (Pearson coefficients) of the correlation obtained from pregabalin vs. placebo will be compared.
Time frame: Baseline to week 4
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Pregabalin | Change in Spontaneous Pain Intensity as a Function of Baseline MPT | -0.0179 Pearson correlation coefficient |
| Placebo | Change in Spontaneous Pain Intensity as a Function of Baseline MPT | -0.0172 Pearson correlation coefficient |
Secondary
Absolute Change in Pain Intensity, Measured on 0-10 Numerical Rating Scale (NRS)
Absolute change in pain intensity on 0-10 numerical rating scale (NRS) from baseline to 4 weeks with pregabalin vs. placebo NRS: 0= no pain, 10= worst pain
Time frame: Baseline to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Absolute Change in Pain Intensity, Measured on 0-10 Numerical Rating Scale (NRS) | -1.0 units on a scale (0-10 NRS) | Standard Deviation 1.13 |
| Placebo | Absolute Change in Pain Intensity, Measured on 0-10 Numerical Rating Scale (NRS) | 0.3 units on a scale (0-10 NRS) | Standard Deviation 1.1 |
Secondary
Change in BPI Outcomes (INTERFERENCE)
Change from baseline to week 4 in BPI (Brief Pain Inventory) pain interference score BPI interference score is expressed on 0-10 scale, with 0 being the minimum (least), and 10 being the maximum (worst) pain interference
Time frame: baseline to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change in BPI Outcomes (INTERFERENCE) | -0.6 units on a scale (0-10 BPI interference) | Standard Deviation 1.64 |
| Placebo | Change in BPI Outcomes (INTERFERENCE) | -0.2 units on a scale (0-10 BPI interference) | Standard Deviation 1.1 |
Secondary
Change in BPI Outcomes (SEVERITY)
Change from baseline to week 4 in BPI (Brief Pain Inventory) pain severity severity score BPI severity score is expressed on 0-10 scale, with 0 being the minimum (least), and 10 being the maximum (worst) pain severity
Time frame: Baseline to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change in BPI Outcomes (SEVERITY) | -0.8 units on a scale (0-10 BPI severity) | Standard Deviation 1.52 |
| Placebo | Change in BPI Outcomes (SEVERITY) | -0.1 units on a scale (0-10 BPI severity) | Standard Deviation 1.14 |
Secondary
Change in NPSI Outcomes
Change from baseline to week 4 in total NPSI (Neuropathic Pain Symptom Inventory) score The total NPSI score is comprised by adding 5 sub-scores (Burning pain, Pressing pain, Paroxysmal pain, Evoked pain, and Paresthesia/Dysesthesia) and is expressed on a 0-100 scale; 0-minimum (least), and 100 maximum (worst) score
Time frame: Baseline to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change in NPSI Outcomes | -9.8 units on a scale (0-100 NPSI score) | Standard Deviation 12.49 |
| Placebo | Change in NPSI Outcomes | 1.8 units on a scale (0-100 NPSI score) | Standard Deviation 20.93 |
Secondary
Change in Sleep Problem Index (SPI) Outcomes
Change from baseline to week 4 in SPI (Sleep Problem Index) score, on 0-100 scale, where 0= best (least) score, and 100= maximum (worst) score
Time frame: Baseline to week 4
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pregabalin | Change in Sleep Problem Index (SPI) Outcomes | -5.1 units on a scale (0-100 SPI) | Standard Deviation 9.45 |
| Placebo | Change in Sleep Problem Index (SPI) Outcomes | -4.1 units on a scale (0-100 SPI) | Standard Deviation 11.64 |
Secondary
Number of Patients With Significant Pain Reduction
Number of patients who experienced 50% or more reduction in average daily pain (on 0-10 NRS, Numerical Rating Scale, where 0=least pain, 10=worst pain)
Time frame: Baseline to week 4
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pregabalin | Number of Patients With Significant Pain Reduction | 5 Participants |
| Placebo | Number of Patients With Significant Pain Reduction | 3 Participants |