Effects of topical gel Silymarin versus placebo as an adjuvant therapy on pain management in patients with painful diabetic neuropathy: a double-blind randomized clinical trial

To assess the effect of topical gel Silymarin versus placebo as an adjuvant therapy on pain management in patients with painful diabetic neuropathy

This is a Phase III double-blind randomized clinical trial with a control group with parallel groups, in which eligible patients will be randomly assigned to the intervention and control groups using block randomization.

This study will be conducted at the Beheshti Hospital in Hamadan city, involving 50 eligible patients with painful diabetic neuropathy. The patients will be randomly assigned to the intervention and control groups through the block randomization. This trial will be double-blinded.

Inclusion criteria: Age of 18 to 65 years Diabetes mellitus type 1 or 2 Painful diabetic neuropathy Exclusion criteria: Pregnancy or breastfeeding Drug abuse Nondiabetic neuropathy Diabetic ulcer Liver or kidney disease

Intervention group: Pregabalin 75 mg tablet at night plus 3% silymarin topical gel twice a day for 2 months Control group: Pregabalin 75 mg tablet at night plus placebo topical gel twice a day for 2 months

Primary outcome: Pain score, quality of life score, Secondary outcome: Local complication (redness, itching)

In this study, random assignment of patients to the intervention and control groups will be carried out using block randomization. To achieve this, four sheets of paper will be prepared - two with the name of the intervention and two with the name of the control. These paper sheets will be pooled and placed in a container. Patients will be selected one at a time without replacement, and for each patient, a paper sheet will be randomly drawn from the container. After each draw, the paper sheets will be returned to the container, and the process will be repeated until the desired sample size is reached.

Both the medications and placebos will have the same shape. Consequently, patients will remain unaware of the type of intervention they receive. Moreover, the randomization process will be conducted by a separate individual from the one who examines the patients, ensuring that the examining person remains unaware of the intervention. The analyzer responsible for evaluating the trial's results will also be kept blind to the type of interventions. Therefore, the trial will be conducted as a double-blind study.