Neuralgia, Postherpetic Neuralgia, Reflex Sympathetic Dystrophy, Complex Regional Pain Syndrome (CRPS)
Conditions
Keywords
neuropathic pain, postherpetic neuralgia, complex regional pain syndrome, reflex sympathetic dystrophy
Brief summary
The purpose of this study is to see if the drug Pennsaid (Diclofenac) can help reduce pain felt by people with chronic nerve pain. The drug will be used 2-4 times each day for 2 weeks. The U.S. Food and Drug Administration (FDA) has approved Pennsaid to treat osteoarthritis (bone pain), but the FDA has not approved Pennsaid to treat neuropathic (nerve) pain. The research study will compare Pennsaid to placebo.
Detailed description
The research study will compare Pennsaid to placebo. The placebo looks like Pennsaid, but it doesn't contain any Pennsaid. The investigators use placebos in research to see if the results are due to the study drug or to other reasons. At some time during the study the investigators will give the patient Pennsaid. At another time, the investigators will give the patient placebo. The investigators are using Quantitative Sensory Testing (QST), which is temperature testing before and after using the study drug to see if Pennsaid is helpful in reducing people's nerve pain. In this test, a small metal plate, about the size of a matchbox, is put on the area where the patient has pain. The plate is connected to a computer that can warm or cool the plate. The patient will use a computer mouse button to tell us when the plate feels warm. The QST machine is approved by the Food and Drug Administration (FDA). It is often used by nerve doctors to see if a person has neuropathy (pain caused by damage to a nerve).
Interventions
DRUGPennsaid
DRUGPlacebo (2.3% DMSO solution)
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Subject will be between 18 and 80 years of age. 2. Subject has not been on Pennsaid or other topical non-steroid anti-inflammatory drugs for at least one month. 3. Subject agrees to make no change in his/her current pain medications during the entire study period. This requirement will ensure that valid comparisons of primary and secondary measures can be made before and after the study. 4. Subject has a VAS pain score of 4 or above at the beginning of the study. 5. Subject has had a neuropathic pain condition such as those listed above for at least three months. This requirement is to avoid clinical uncertainty from an unstable pain condition and to minimize the study variation. 6. Female subjects of childbearing age must have a negative urine pregnancy test at the initial visit.
Exclusion criteria
1. Subject has documented severe liver or renal disease that will affect the elimination of Pennsaid or is subject to the adverse effect of Pennsaid on these organs. (Renal dysfunction is defined as eGFR \< 60. Hepatic dysfunction is defined as LFTs ≥ 3X ULN.) 2. Subject has pending litigation related to the neuropathic pain condition. 3. Subject has active skin lesion or open wound at the site of Pennsaid application (e.g., active shingles with skin lesions). 4. Subject is pregnant or lactating. 5. Subject has scar tissue or sensory deficit at the site of QST. 6. Subject is allergic to diclofenac or has cross-sensitivity to other non-steroid anti-inflammatory drugs. 7. Subject has a positive urine (illicit) drug test. 8. Subjects who experience asthma, urticaria or an allergic type reaction when taking aspirin or NSAIDs. 9. Subjects undergoing coronary artery bypass surgery. 10. Subject with a known history of cardiovascular disease, ulcer, gastrointestinal bleed or impaired renal function. 11. Subjects currently using NSAIDS.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| VAS After Treatment | 2 weeks. | Subjects rated their pain using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Neuropathic Pain Features- Burning After Treatment | 2 weeks | Subjects rated their burning pain using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study. |
| Clinical Neuropathic Pain Features- Constant Pain and Hypersensitivity After Treatment | 2 weeks | Subjects rated their constant pain and hypersensitivity using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pennsaid Phase I Pennsaid (20-40 drops; 2-4 times daily). Upon completion of the first phase, subjects in each arm will be crossed over (i.e., from placebo to Pennsaid and vise versa). Pennsaid or placebo lotion will be packed in a container with identical appearance before being dispensed to study subjects. | 18 |
| Placebo Phase I Placebo lotion (20-40 drops; 2-4 times daily). Upon completion of the first phase, subjects in each arm will be crossed over (i.e., from placebo to Pennsaid and vise versa). Pennsaid or placebo lotion will be packed in a container with identical appearance before being dispensed to study subjects. | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Phase I (2 Weeks) | Medication Exclusion | 1 | 1 |
| Phase I (2 Weeks) | Positive Drug Screen | 0 | 2 |
| Phase I (2 Weeks) | Wrong Pain Type | 1 | 0 |
| Phase II (2 Weeks) | Medication Exclusion | 1 | 0 |
| Phase II (2 Weeks) | Skin Sensitivity | 0 | 1 |
Baseline characteristics
| Characteristic | Pennsaid Phase I | Placebo Phase I | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 15 Participants | 32 Participants |
| Gender Female | 9 Participants | 8 Participants | 17 Participants |
| Gender Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 33 |
| serious Total, serious adverse events | 0 / 32 | 0 / 33 |
Outcome results
Primary
VAS After Treatment
Subjects rated their pain using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study.
Time frame: 2 weeks.
Population: Only subjects who completed both phases of the crossover study were considered for data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pennsaid | VAS After Treatment | 4.9 Visual Analog Scale | Standard Deviation 1.9 |
| Placebo | VAS After Treatment | 5.6 Visual Analog Scale | Standard Deviation 2.1 |
p-value: 0.04t-test, 2 sided
Secondary
Clinical Neuropathic Pain Features- Burning After Treatment
Subjects rated their burning pain using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study.
Time frame: 2 weeks
Population: Only subjects
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pennsaid | Clinical Neuropathic Pain Features- Burning After Treatment | 2.9 Visual Analog Scale | Standard Deviation 2.6 |
| Placebo | Clinical Neuropathic Pain Features- Burning After Treatment | 4.3 Visual Analog Scale | Standard Deviation 2.8 |
Secondary
Clinical Neuropathic Pain Features- Constant Pain and Hypersensitivity After Treatment
Subjects rated their constant pain and hypersensitivity using the Visual Analog Scale after a 2 week phase of using pennsaid lotion and after a 2 week phase of using placebo lotion. The Visual Analog Scale is subject reported on a scale of 0-10 with 0 being no pain, and 10 being the worst pain they can imagine. Results reported are an average of reported VAS scores for the 28 subjects who completed both phase I and phase II of the study.
Time frame: 2 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pennsaid | Clinical Neuropathic Pain Features- Constant Pain and Hypersensitivity After Treatment | 4.0 Visual Analog Scale | Standard Deviation 2.9 |
| Placebo | Clinical Neuropathic Pain Features- Constant Pain and Hypersensitivity After Treatment | 4.3 Visual Analog Scale | Standard Deviation 2.8 |