Effects of Pennsaid on Clinical Neuropathic Pain

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).

• Pennsaid (Drug), also known as Pennsaid topical 1.5% diclofenac, a non-steroid anti-inflammatory drug
• Placebo (2.3% DMSO solution) (Drug), also known as Placebo (2.3% DMSO solution; 20-40 drops; 2-4 times daily).

Primary outcomes

• 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 outcomes

• 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.

Sex: All, ages: 18 Years to 80 Years

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.

Participant flow

Outcome results

• VAS After Treatment (Primary), Mean, Visual Analog Scale: Pennsaid 4.9 +/- 1.9; Placebo 5.6 +/- 2.1 (p .04)
• Clinical Neuropathic Pain Features- Burning After Treatment (Secondary), Mean, Visual Analog Scale: Pennsaid 2.9 +/- 2.6; Placebo 4.3 +/- 2.8
• Clinical Neuropathic Pain Features- Constant Pain and Hypersensitivity After Treatment (Secondary), Mean, Visual Analog Scale: Pennsaid 4.0 +/- 2.9; Placebo 4.3 +/- 2.8

Adverse events

Time frame: Adverse event data was collected over the length of a subject's participation in the study (5 weeks).

• Jianren Mao, M.D., Ph.D., Principal investigator, DACCPM