Painful Diabetic Peripheral Neuropathy
Conditions
Brief summary
This study will evaluate the efficacy and safety of low-dose duloxetine combined with alpha-lipoic acid compared with standard-dose duloxetine in adults with painful diabetic peripheral neuropathy. In this assessor-blinded, randomized, parallel-arm, non-inferiority trial, participants will be assigned in a 1:1 ratio to receive either duloxetine 30 mg once daily plus alpha-lipoic acid 600 mg once daily or duloxetine 60 mg once daily. The primary outcome will be the change in pain intensity measured by the Numerical Rating Scale from baseline to Week 9. Secondary outcomes will include changes in pain intensity at Week 5, Patient Global Impression of Change at Weeks 5 and 9, the proportion of participants achieving at least a 30% reduction in pain intensity, adverse effects, treatment tolerability and treatment compliance.
Detailed description
Painful diabetic peripheral neuropathy (PDPN) is a common and clinically important complication of diabetes mellitus, characterized by chronic neuropathic pain that can substantially impair physical functioning, sleep, daily activities, and quality of life. Duloxetine is an established pharmacological treatment for PDPN; however, the standard dose of 60 mg once daily may be associated with dose-related adverse effects and may not be well tolerated by all patients. Alpha-lipoic acid has antioxidant and neuroprotective properties and has also been studied as an adjunctive treatment for diabetic neuropathy. This study is designed to evaluate whether a low-dose duloxetine regimen combined with alpha-lipoic acid provides pain relief that is not inferior to standard-dose duloxetine while maintaining an acceptable safety and tolerability profile. This will be a single-centre, parallel-arm, assessor-blinded, randomized controlled non-inferiority trial involving adults with painful diabetic peripheral neuropathy. Participants who meet the eligibility criteria and provide informed consent will be randomly allocated in a 1:1 ratio to one of two treatment groups. Participants in Group A will receive duloxetine 30 mg once daily plus alpha-lipoic acid 600 mg once daily. Participants in Group B will receive duloxetine 60 mg once daily. During the first week, both groups will receive duloxetine 30 mg once daily. From Week 2 onward, Group A will continue duloxetine 30 mg once daily plus alpha-lipoic acid 600 mg once daily, whereas Group B will receive duloxetine 60 mg once daily. Participants will be followed for 9 weeks. Telephone follow-ups will be conducted at Weeks 1 and 3 to assess safety and treatment adherence. Scheduled outpatient department visits will be conducted at Weeks 5 and 9 for clinical assessment and outcome evaluation. Paracetamol will be permitted as a protocol-specified rescue medication for breakthrough pain, and its use will be documented throughout the study. The primary outcome will be the change in pain intensity measured by the Numerical Rating Scale (NRS) from baseline to Week 9. Secondary outcomes will include change in NRS at Week 5; Patient Global Impression of Change (PGIC) at Weeks 5 and 9; the proportion of participants achieving at least a 30% reduction in NRS from baseline; frequency and pattern of adverse effects; treatment tolerability; and treatment compliance. The study will determine whether the low-dose duloxetine plus alpha-lipoic acid regimen is non-inferior to standard-dose duloxetine in reducing pain intensity in adults with PDPN, while also comparing safety, tolerability, adherence, and other clinical outcomes between the two treatment groups.
Interventions
DRUGDuloxetine
Duloxetine will be administered orally once daily. During Week 1, all participants will receive duloxetine 30 mg once daily. From Week 2 onward, participants in the low-dose combination group will continue duloxetine 30 mg once daily in combination with alpha-lipoic acid 600 mg once daily, whereas participants in the standard-dose duloxetine group will receive duloxetine 60 mg once daily. Treatment will continue through Week 9.
Alpha-lipoic acid 600 mg will be administered orally once daily in combination with duloxetine 30 mg once daily to participants assigned to the low-dose combination group. Treatment will be administered from Week 2 through Week 9.
Sponsors
Bangladesh Medical University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Participants will be randomly assigned in a 1:1 ratio to one of two parallel treatment groups. Group A will receive duloxetine 30 mg once daily plus alpha-lipoic acid 600 mg once daily, while Group B will receive duloxetine 60 mg once daily. Both groups will receive duloxetine 30 mg once daily during Week 1; from Week 2 onward, Group A will continue duloxetine 30 mg plus alpha-lipoic acid 600 mg once daily, whereas Group B will receive duloxetine 60 mg once daily.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years. * Diagnosed case of diabetes mellitus. * Diabetic peripheral neuropathy diagnosed clinically according to the Toronto Clinical Neuropathy Score (TCNS) criteria with a TCNS score ≥6, with painful neuropathy confirmed using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) Pain Scale with a score ≥12. * Duration of neuropathic symptoms ≥3 months. * Baseline Numerical Rating Scale (NRS) pain score ≥4. * Willingness to participate in the study and provide written informed consent.
Exclusion criteria
* Pain attributable to causes other than diabetic peripheral neuropathy, such as peripheral arterial disease (ischaemic pain), osteoarthritis, inflammatory arthritis, phantom limb pain, radiculopathy, or other chronic pain disorders. * Known vitamin B12 deficiency, hypothyroidism, chronic alcohol use, hereditary neuropathy, chemotherapy-induced neuropathy, HIV infection, or connective tissue disease. * Chronic kidney disease (CKD) stage ≥4. * Chronic liver disease or significant hepatic impairment (ALT \>3 times the upper normal limit). * Use of antidepressants, antiepileptic drugs, sedatives, antipsychotic drugs, or opioids within the preceding 4 weeks. * Pregnancy or lactation, or women planning pregnancy during the study period. * Known hypersensitivity or contraindication to duloxetine or alpha-lipoic acid. * Major depressive disorder as assessed by the Patient Health Questionnaire-9 (PHQ-9), cognitive impairment (MMSE \<24), active malignancy, or any serious medical condition that, in the opinion of the investigator, may interfere with study participation, treatment adherence, or outcome assessment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in pain intensity measured by Numerical Rating Scale (NRS) from baseline to Week 9 | From baseline to Week 9 | Change in pain intensity from baseline to Week 9, measured using the Numerical Rating Scale (NRS), a 0-10 scale in which 0 indicates no pain and 10 indicates the worst possible pain. Higher scores indicate worse pain and therefore a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in pain intensity measured by Numerical Rating Scale (NRS) from baseline to Week 5 | From baseline to Week 5 | Change in pain intensity from baseline to Week 5, measured using the Numerical Rating Scale (NRS), a 0-10 scale in which 0 indicates no pain and 10 indicates the worst possible pain. Higher scores indicate worse pain and therefore a worse outcome. |
| Patient Global Impression of Change (PGIC) | Week 5 and Week 9 | Patient-reported global assessment of change in painful diabetic peripheral neuropathy symptoms using the Patient Global Impression of Change (PGIC), a 7-point scale ranging from 1 (very much improved) to 7 (very much worse), with 4 indicating no change. Lower scores indicate greater improvement and therefore a better outcome. |
| Proportion of participants achieving ≥30% reduction in pain intensity | Week 5 and Week 9 | Proportion of participants achieving a ≥30% reduction in pain intensity from baseline to Week 9, measured using the Numerical Rating Scale (NRS), a 0-10 scale in which 0 indicates no pain and 10 indicates the worst possible pain. A reduction in NRS score indicates improvement. |
| Incidence, type, frequency, and severity of treatment-emergent adverse events | Baseline to Week 9 | Type, frequency, and severity of adverse events occurring during the study period. Adverse events will be assessed and recorded from baseline through Week 9, including events leading to treatment discontinuation. |
| Proportion of participants discontinuing treatment due to adverse events | Baseline to Week 9 | Proportion of participants who discontinue study treatment because of adverse events occurring during the study period. |
| Treatment compliance | Baseline to Week 9 | Proportion of prescribed study medication doses taken during the study period. |
Countries
Bangladesh
Contacts
CONTACTMd. Nazmul Hussain, MBBS
Outcome results
None listed