Muscarinic Receptor Antagonists as a Therapy for Diabetic Neuropathy

Study Summary

Investigators propose a placebo controlled, double blinded study to examine efficacy of topical Gelnique 3%TM (3% oxybutynin) daily for 20 weeks) in improving IENF density in type 2 diabetic subjects with established peripheral neuropathy. This site most clearly demonstrated efficacy of topiramate in reversing IENF loss within 18 weeks in our prior study. Subjects will also undergo quantitative sensory testing (QST) and assays of laser Doppler skin blood flow (SkBF), neuropathy total symptom score (NTSS-6), and quality of life (Norfolk QOL-DN), along with standard measures of physiology and fasting blood chemistry. Subjects with IENF loss of between 20-75% of normative values and thus amenable to therapy-induced recovery, will be randomized into placebo (N=30) or active drug (N=30) arms and instructed in how to apply 84 mg Gelnique 3%TM or hydrogel placebo to cover a 2 in2 region of skin adjacent to the initial biopsy site, as per the manufacturers instructions (http://www.gelnique.com/gel3/). Treatment will continue daily for 20 weeks, with monthly phone calls to monitor compliance. After 20 weeks, subjects will return for a second series of measurements and 3 mm skin biopsy from the treated region of skin.

Primary Outcome

Three mm skin biopsies will be taken at the two sites (lateral aspect of the proximal lower limb), on the non-dominant limb. Patients are pre-treated with 2% lidocaine with epinephrine and the biopsy is done with a sharp punch biopsy. All biopsy procedures are performed by a physician or physician's assistant under sterile conditions. Once removed the tissues are immediately transferred to storage buffer and frozen prior to sectioning and immunohistochemistry staining with PGP 9.5. Intraepiderma

Interventions

• DRUG Placebo
• DRUG 3% oxybutynin