Painful diabetes-related peripheral neuropathy Nervous System Diseases
Conditions
Interventions
Design: A pragmatic, multi-centre, two-arm, parallel-group, double-blind, sham-controlled, randomised trial with an internal pilot.
Target population: 356 adults with PDPN for =3 months with signific
Sponsors
University of Birmingham
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 15/04/2025: 1. Aged =18 years 2. Neuropathic pain affecting both feet for =3 months or taking pain medication for neuropathic pain for =3 months 3. Mean pain score =4 on the daily NRS =4 weeks prior to randomisation 4. Douleur Neuropathique 4 (DN-4) questionnaire score =4/10 at screening to confirm the diagnosis of bilateral distal symmetrical neuropathic pain [70] 5. Diabetes-related neuropathy based on the Michigan Neuropathy Screening Instrument (MNSI) (MNSI questionnaire scored =7 or examination scored >2) [71, 72] 6. HbA1c 2) 6. HbA1c <108 mmol/mol or 12% (within the last 2 months) 7. Have tried at least two drugs from two different classes for PDPN 8. Willing and able to comply with the study schedule and be available for the treatment duration 9. Able to give written informed consent
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 15/04/2025: 1. Non-diabetic neuropathies 2. Currently using TENS for PDPN 3. History of epilepsy 4. Other painful medical conditions where the pain is significantly more severe than their PDPN pain (patients will not be excluded if the pain is transient in nature) 5. Major amputations of the lower limbs 6. Active diabetic foot ulcers 7. Active malignancy 8. Patient has a pacemaker, defibrillator or neurostimulator 9. Pregnancy Previous exclusion criteria: 1. Non-diabetic neuropathies 2. Currently using TENS for PDPN 3. History of epilepsy 4. Other painful medical conditions where the pain is significantly more severe than their PDPN pain (patients will not be excluded if the pain is transient in nature) 5. Major amputations of the lower limbs 6. Active diabetic foot ulcers 7. Diagnosed malignancy 8. Pacemakers, defibrillator or neurostimulator 9. Pregnancy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 7-day average 24-hour pain on an 11-point NRS scale (0 = no pain and 10 = worst pain imaginable) measured at 3 months post-randomisation | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 15/04/2025: Clinical: 1. 7-day average 24-hour pain measured on an 11-point NRS scale at the end of treatment and 6 months 2. Disease-specific quality of Life (QoL) measured using the Neuropathic Pain Impact on Quality-of-Life Questionnaire (NePIQoL) at 3 and 6 months 3. Treatment success (measured as a 30% reduction in 7-day average 24-hour pain scores) at the end of treatment, 3 and 6 months 4. Treatment success (measured as a 50% reduction in 7-day average 24-hour pain scores) at the end of treatment, 3 and 6 months 5. Area Under the Curve (AUC) for the daily NRS pain scores over the study period (from baseline to 3 months and from baseline to 6 months) 6. Pain interference with function measured using the Brief Pain Inventory-Diabetic Peripheral Neuropathy (BPI-DPN) at 3 and 6 months 7. Depression measured using the Beck Depression Inventory at 3 and 6 months 8. Sleep quality measured using the Pittsburgh Sleep Quality Index (PSQI) at 3 and 6 months 9. Pain intensity measured using the Neuropathic Pain Symptom Inventory (NPSI) at the end of treatment, 3 and 6 months. 10. Participant ratings of overall improvement, assessed by the Patients' Global Impression of Change (PGIC) and Clinician Global Impression of Change (CGIC) with a 7-point Likert scale at the end of treatment, 3 and 6 months 11. Changes to pain medications (frequencies and dosages) measured using patient-reported outcomes/clinical examination and interview with the patient at 3 and 6 months 12. Patient perception of their treatment arm, documented on the end-of-treatment participant case report form (CRF) by the patient. The patient has the option to select if they think they received FREMS or TENS. Measured at the end of the treatment phase. Cost-effectiveness: 1. Health-related QoL assessed by the EQ-5D-5L at 6 months 2. Health resource use measured using the Health Economic Questionnaire at 3 and 6 months 3. Cost per quality-adjusted life year (QALY) gai | — |
Countries
England, United Kingdom, Wales
Outcome results
None listed