Overview
The purpose of this clinical trial is to compare the efficacy of benfotiamine with vitamin B1-6-12 in reducing sensory neuropathy symptoms, numbness and pain in patients with diabetic peripheral neuropathy.
The main questions this study aims to answer are:
- Does benfotiamine reduce overall sensory neuropathy symptoms more effectively than vitamin B1-6-12?
- Does benfotiamine reduce numbness more effectively than vitamin B1-6-12?
- Does benfotiamine reduce pain more effectively than vitamin B1-6-12?
Researchers will compare benfotiamine with vitamin B1-6-12 in a double-blind study. Both treatments will be manufactured as visually identical study medications to maintain blinding.
The study will evaluate whether benfotiamine provides greater improvement in sensory neuropathy symptoms, numbness, and pain than vitamin B1-6-12 in patients with diabetic peripheral neuropathy.
Participants will:
- undergo screening for vitamin B12 deficiency before enrollment. Patients with vitamin B12 deficiency will not be eligible for participation.
- randomly assigned to receive either benfotiamine or vitamin B1-6-12, taken orally twice daily for 3 months.
- attend two on-site clinic visits (baseline and the end of the study) and complete two telephone follow-up assessments during the study.
- continue their usual medications throughout the study, provided that no new neuropathic pain medications are initiated and the dose of existing neuropathic pain medications remains unchanged.
Eligibility
Inclusion Criteria:
- Age ≥18 years.
- Diagnosis of diabetic peripheral neuropathy confirmed by a physician based on the following ICD-10 codes: E11.42: Type 2 diabetes mellitus with diabetic polyneuropathy; or E11: Type 2 diabetes mellitus, combined with either:
M79.2: Neuralgia and neuritis, unspecified; or G62.9: Polyneuropathy, unspecified.
- Presence of sensory neuropathy symptoms assessed using the Neuropathy Total Symptom Score-6 (NTSS-6), with: Total NTSS-6 score ≥1; and Numbness symptom score (NTSS-6 item 6) ≥1.
- No evidence of vitamin B12 deficiency, defined as a serum vitamin B12 level ≥200 pg/mL (148 pmol/L).
- provide informed consent and participate in the study.
Exclusion Criteria:
- Presence of fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltose malabsorption.
- Adjustment of doses of medications used for neuropathic pain control within 6 weeks prior to study enrollment, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, or other neuropathic pain medications.
- Presence of other conditions that may affect diabetic peripheral neuropathy or neuropathic pain, including:
- Chemotherapy-induced peripheral neuropathy due to neurotoxic agents within 6 months prior to enrollment, including vinca alkaloids, taxanes, platinum-based agents, proteasome inhibitors, thalidomide, brentuximab vedotin, or ado-trastuzumab emtansine.
- HIV/AIDS with any of the following: Current or previous treatment with didanosine, stavudine, or zalcitabine; CD4 count \<200 cells/mm³; or HIV viral load \>1,000 copies/mL.
- Drug-induced polyneuropathy (ICD-10: G62.0).
- Polyneuropathy due to other toxic agents (ICD-10: G62.2).
- Alcoholic polyneuropathy (ICD-10: G62.1).
- Fibromyalgia (ICD-10: M79.7).
- Planned surgery within 3 months prior to or during the study period.
- Previous pain-relief procedures, including:
- Transcutaneous electrical nerve stimulation (TENS) or temporary peripheral nerve stimulation (PNS) within 1 year prior to enrollment;
- Permanent PNS;
- Pulsed radiofrequency or radiofrequency ablation within 6 months prior to enrollment;
- Botulinum toxin injection for neuropathic pain relief within 12 weeks prior to enrollment.
- Adjustment of glucose-lowering medication doses or HbA1c \>8% within 3 months prior to study enrollment.
- Pregnancy, planned pregnancy within 3 months, or currently breastfeeding.
- Inability to attend scheduled study visits in person or through telemedicine follow-up as required by the study protocol.
- Known allergy or hypersensitivity to benfotiamine or any component of benfotiamine, vitamin B1, vitamin B6, or vitamin B12.
- Previous use of benfotiamine and/or vitamin B1-6-12 discontinued less than 7 days before study enrollment.
- Current use of vitamin B6 supplementation or medications containing vitamin B6 at a dose \>100 mg/day.
