Comparison of the efficacy of duloxetine and bupropion in reducing neuropathic pain due to diabetic neuropathy: a randomized triple-blind clinical trial

To evaluate the effect of duloxetine and bupropion on neuropathic pain reduction and quality of life improvement in patients with diabetic neuropathy

Randomized triple-blind clinical trial with three parallel groups, total sample 300, allocation concealment using sealed envelopes

This study is a triple-blind, randomized clinical trial with three parallel groups conducted at Shahid Beheshti Hospital, Qom, targeting patients with diabetes-related neuropathic pain who visit this center. Eligible patients, after providing written informed consent, are randomly assigned using Random Allocation Software to one of three groups (Bupropion, Duloxetine, or Control/Placebo), and the interventions continue for four weeks. The active drugs and placebos are identical in appearance, color, size, packaging, and administration, allowing participant-level blinding. The study is conducted in a triple-blind manner, meaning that participants, evaluating physicians, clinical care staff, and data analysts are unaware of group assignments, while only the responsible pharmacist has access to the randomization codes. This approach ensures unbiased data collection, outcome assessment, and result analysis.

Inclusion: Patients over 18 years with type 1 or 2 diabetes, symptomatic peripheral neuropathy with pain ≥4/10, stable standard treatment, informed consent Exclusion: Other causes of neuropathy, drug hypersensitivity, severe hepatic or renal disease, severe psychiatric disorders, pregnancy or breastfeeding

Group 1: Bupropion 75 mg twice daily + duloxetine placebo Group 2: Duloxetine 60 mg daily + bupropion placebo Group 3: Placebo + matching placebos (control group)

Neuropathic pain intensity measured by VAS at baseline, week 4, and three months follow-up

The study is designed as a triple-blind, randomized clinical trial with three parallel groups, and the unit of randomization is individual patients. Eligible participants are randomly assigned to one of the three groups. The random sequence was generated using Random Allocation Software with fixed-size blocks of 6 or 9 patients per block to ensure balanced group sizes. No stratified randomization was used in this study. For allocation concealment, the randomization codes were placed in sealed, numbered envelopes, accessible only to the responsible pharmacist. Patients, evaluating physicians, and data analysts are blinded to group assignments, ensuring that the study is conducted in a triple-blind manner.

In this study, the active drugs and placebos are identical in appearance, color, size, packaging, and administration, allowing for participant-level blinding. The trial is conducted as a triple-blind study, meaning that participants, evaluating physicians and clinical care staff, and data analysts are unaware of the group assignments. The pharmacist responsible for dispensing the medications is the only individual with access to the randomization codes, and no other research team members are informed of patient allocation. This approach ensures unbiased data collection, outcome assessment, and result analysis. The Data Safety and Monitoring Committee and the team preparing manuscripts also have no access to group assignments. It should be noted that participants are not informed of their assigned group, solely to maintain blinding, and this is conducted in full compliance with ethical standards and informed consent requirements.

De-identified individual participant data (IPD) related to the primary and secondary outcomes of the clinical trial: "Determining the effect of Duloxetine in reducing neuropathic pain compared to Bupropion".

Data will become available 6 months after the publication of the primary results of the trial and will remain accessible for a period of 5 years.

Access will be granted to researchers affiliated with academic or scientific institutions who provide a methodologically sound research proposal. Access for commercial or for-profit entities is not permitted.

The data can only be used for the purpose of conducting individual participant data meta-analysis, reanalysis for validation, or other scientifically approved questions as outlined in the approved research proposal. All users must sign a Data Use Agreement committing to: 1) Not attempting to re-identify participants, 2) Securely storing the data, 3) Not transferring the data to third parties, 4) Acknowledging the original study in any publications, and 5) Destroying the data after the completion of their analysis.

All requests must be sent via email to the principal investigator of the study (drmaryamamini6771@yahoo.com) and should include the research proposal and the requester’s institutional affiliation details. The principal investigator and holder of the study is Ms. Maryam Mirzaamini

Submission of a formal request via email. 2. Initial review by the PI for completeness. 3. Evaluation of the scientific merit and objectives by a designated data access committee (DAC) within 4 weeks. 4. If approved, preparation and execution of the Data Use Agreement. 5. Secure transfer of de-identified data in a common format (e.g., .csv, .sav). The entire process is expected to take 6 to 8 weeks from initial request to data transfer.

The study protocol, statistical analysis plan (SAP), and analytic code will be made publicly available on a recognized repository (e.g., ClinicalTrials.gov or OSF) upon completion of participant enrollment.