The goal of this clinical trial is to evaluate the efficacy of thymoquinone as an adjuvant treatment with pregabalin in the management of diabetic peripheral neuropathy for both sexes older than 18 years.

The main questions it aims to answer are:

• Whether the use of thymoquinone could improve diabetic neuropathy and be confirmed by a nerve conduction study?
• Could thymoquinone improve oxidative stress and inflammation by using these parameters (visfatin, calprotectin, malondialdehyde)?
• Does thymoquinone improve neuropathic pain by using the VAS scale for pain?

Study Design and Methodology This is a randomized, clinical trial designed to evaluate the neuroprotective effects of thymoquinone in diabetic patients with neuropathy.

Study Sites Primary Location: Galyawa diabetic center and Neurophysiology Department of Hawler Psychiatric Hospital, affiliated with Hawler Medical University.

Multicenter expansion was considered, but all participants were recruited at the primary site.

Study Population Enrollment (Actual): 50 participants with diabetic neuropathy Groups: Group 1 (n=25): DPN patients on Pregabalin 75 mg daily for 2 months. Group 2 (n=25): DPN patients on Pregabalin 75 mg + Thymoquinone 65 mg daily for 2 months.

Follow-up Period Duration: 2 months from initiation of treatment. Assessment intervals: Baseline (pre-treatment) and 2 months (post-treatment). Primary outcome: A Nerve conductive study was done, and blood samples for (visfatin, calprotectin, malondialdehyde, and HbA1c) measurement were drawn before starting treatment.

Secondary or Endpoints: the same investigations were done after two months of treatment Adverse Events: Monitored continuously throughout the 2-month treatment and follow-up, including risks of epigastric pain, dizziness, and headache.

Statistical Analysis Plan Sample Size: Originally planned for 80 patients, but 50 were enrolled (25 per group).

Comparative Analysis: Paired t-tests, Wilcoxon signed-rank tests (for non-parametric data), ANOVA for repeated measures where appropriate.

Ethical Considerations Approved by the Hawler Medical University Ethics Committee.

Written informed consent was obtained from all participants. Potential Impact: If thymoquinone proves effective, this study could support the use of thymoquinone as a neuroprotective strategy in diabetic neuropathic patients, improving NCS outcomes and quality of life.

Inclusion Criteria:

1. Both males or females of any race over 18 years of age.
2. Patients with either type1 or type2 diabetes, who have been on a stable anti-diabetic medication regimen for at least 30 days before randomization.
3. Duration of painful diabetic peripheral neuropathy was required to be more than 3 months.

Exclusion Criteria:

1. History of smoking, alcohol consumption, and thyroid gland disorder.
2. Patients with any kidney disorder or any conditions that could confound the assessment of pain due to diabetic peripheral neuropathy.

At this time, individual participant data (IPD) will not be shared publicly. The data will be kept confidential to ensure participant privacy and comply with ethical and regulatory requirements, including those related to informed consent and data protection. Access to the data may be considered for future collaborations under strict ethical guidelines and approval from the relevant oversight bodies.