Description

Diabetic symmetrical polyneuropathy (DSPN) is a common chronic complication of diabetes mellitus. It is characterized by symmetrical, length-dependent damage to peripheral nerves and may cause pain, burning sensations, numbness, tingling, weakness, and loss of protective sensation. Loss of protective sensation may increase the risk of foot injury, ulceration, infection, and other diabetic foot complications.

Alpha-lipoic acid (ALA) and vitamin E have antioxidant properties and have been studied for their potential roles in reducing oxidative stress associated with diabetic neuropathy. Vitamins B1, B6, and B12 have roles in normal nerve function and have also been used in the management of neuropathy. This study is therefore evaluating whether adding ALA and vitamin E to a vitamin B combination provides additional benefits for participants with DSPN.

This is a single-centre open label study being conducted at the Hospital Canselor Tuanku Muhriz (HCTM) Orthopaedic Clinic. A total of 100 participants are being recruited, with 50 participants being assigned to each treatment group. Participants are being randomized into two groups, and independent personnel are responsible for the randomization and distribution of the study treatments. The study population consists of adults with type 2 diabetes mellitus and symptoms of DSPN who are being followed at the HCTM Orthopaedic Outpatient Clinic. DSPN is being assessed using the Toronto Clinical Neuropathy Scoring (TCNS) system.

Participants are receiving one of two oral treatment regimens for 12 consecutive weeks in addition to standard treatment for DSPN. The first group is receiving Bionerv-E+. Each tablet contains alpha-lipoic acid 300 mg, vitamin B12 500 micrograms, vitamin B1 39 mg, vitamin B6 8 mg, and vitamin E 100 IU. Participants in this group are taking two tablets once daily after a meal. The second group is receiving a vitamin B-complex. Each tablet contains vitamin B12 200 micrograms, vitamin B6 200 mg, and vitamin B1 100 mg. Participants in this group are taking three tablets once daily after a meal.

Participants are undergoing a baseline clinical assessment before starting treatment and are being reassessed after the 12-week treatment period. Neurological impairment in the lower limbs is being evaluated using the Neuropathy Impairment Score-Lower Limb (NIS-LL). The NIS-LL assesses motor, sensory, and reflex function and is being administered by a medical officer. Pain is being assessed using the Short Form McGill Pain Questionnaire (SF-MPQ). Quality of life is being evaluated using the Short Form-36 (SF-36), which assesses physical and mental aspects of health across eight domains.

The study is also investigating whether the treatments have different effects on systemic inflammation. Blood samples are being collected at recruitment and after the treatment period to measure high-sensitivity C-reactive protein (hs-CRP) and tumor necrosis factor-alpha (TNF-alpha). For each assessment, 10 mL of venous blood is being collected after overnight fasting. The inflammatory biomarkers are being measured using enzyme-linked immunosorbent assay (ELISA) methods.

The study is also evaluating wound healing in participants with diabetic foot ulcers. The study is focusing on eligible non-healing ulcers classified as Wagner grade 1 or 2. For wound assessment, researchers are documenting the wound history and evaluating wound size and clinical characteristics. Wound dimensions are being measured, and digital imaging is being used to calculate wound area at baseline and after treatment. Researchers are also monitoring clinical features associated with infection, including edema, erythema, discharge, pain, and fever. Wounds are being classified according to their location and evaluated using the Wagner classification. Debridement is being performed to remove hyperkeratosis and callus when applicable.

At recruitment, informed consent is being obtained before study procedures are performed. Baseline information being collected includes demographic and clinical data, neurological assessments, pain assessment, quality-of-life assessment, inflammatory biomarkers, and wound examination where applicable. Participants are receiving a follow-up telephone call during week 7 to support treatment adherence. They are returning for reassessment at week 13, after completing 12 weeks of treatment. At this visit, neurological impairment, pain, quality of life, inflammatory biomarkers, and wound status are being reassessed. Treatment adherence is also being evaluated using pill counts and medication diaries.

The study is using an intention-to-treat approach for data analysis. Descriptive statistics are being used to summarize demographic characteristics. The distribution of study data is being assessed for normality, followed by appropriate bivariate and multivariate analyses. The planned analyses include t-tests, Mann-Whitney U tests, paired comparisons, and multiple linear regression. A p-value below 0.05 is being considered statistically significant.