Neuromuscular Electrical Stimulation For The Treatment of Diabetic Neuropathy

Study Overview
=================
Brief Summary
-----------------
Diabetic neuropathy (DN) is the most common complication of diabetes, affecting almost 50% of people with diabetes over the course of their lives. Symptoms vary from numbness to burning, aching and hypersensitivity in the lower limbs, indicative of sensory nerve loss. Motor neurons can also be affected, leading to muscle weakness and mobility issues, thus preventing patients from engaging in daily routines. Further sequelae include foot ulceration and Charcot neuroarthropathy, which are risk factors for lower limb amputation and mortality. In the United Kingdom, the annual costs of DN alone exceed £300 million, with further complications expected to cost an additional £1 billion. Currently, management strategies for DN focus on prevention and pain management. Neuromuscular electrical stimulation (NMES) is a novel nonpharmacological intervention for people with DN. NMES is the application of electrical impulses which are of sufficiency intensity to improve artificial contraction of the muscle tissue and may help with DN by improving nerve conductivity through direct stimulation of the nerves.

Official Title
-----------------
Neuromuscular Electrical Stimulation For The Treatment Of Diabetic Neuropathy: A Multicentre, Double-blind, Pilot, Randomised, Sham-controlled Trial

Conditions
-----------------
Diabetic Neuropathies, Diabetic Polyneuropathy, Diabetic Complication, Diabetic Peripheral Neuropathy

Intervention / Treatment
-----------------
* Device: Revitive Medic Coach (Actegy Ltd)
* Device: Sham Revitive Medic Coach (Actegy Ltd)


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA Aged ≥18 (no upper limit) Diagnosis of type 1 or type 2 diabetes based on World Health Organisation (WHO) definition Diagnosis of diabetic neuropathy based on: symptoms of diabetic neuropathy validated screening questionnaire Michigan Neuropathy Screening Instrument score of ≥4 nerve conduction study of at least one lower limb must have a sural SNAP amplitude of <6 μV or absent Access to internet at home to use the Revitive App (study smartphones will be provided) Personal mobile phone to receive text messages EXCLUSION CRITERIA Lacks capacity to provide informed consent Pregnant Implanted electronic, cardiac or defibrillator device Other cause of peripheral neuropathy (e.g. excessive drinking, low levels of vitamin B12 or other vitamins, syphilis, HIV, underactive thyroid gland) Current foot ulceration Severe vascular disease requiring invasive intervention Being treated for, or have the symptoms of, an existing deep vein thrombosis (DVT) Used a neuromuscular electrical stimulation (NMES) device within 1 year of randomisation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control group<br>Best Medical Therapy + Sham Revitive Medic Coach (Sham Neuromuscular Electrical Stimulation Device) for 6 months | Device: Sham Revitive Medic Coach (Actegy Ltd)<br>* Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).<br>* Other names: Sham Footplate Neuromuscular Electrical Stimulation Device;|
| Active Comparator: Intervention group<br>Best Medical Therapy + Revitive Medic Coach (Neuromuscular Electrical Stimulation Device) for 6 months | Device: Revitive Medic Coach (Actegy Ltd)<br>* Use the device for two 30-minute sessions per day, a minimum of five hours per week for 6 months at suprathreshold (2 x motor threshold).<br>* Other names: Footplate Neuromuscular Electrical Stimulation Device;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary outcome measure: sural nerve conductivity measured using a nerve conduction study at 6 months. This includes conduction velocity (m/s), calculated using distance and latency (ms), and sensory nerve action potential (SNAP) amplitude (μV). | Multi-component, single outcome. Nerve conduction parameters include sural nerve conduction velocity (m/s) and SNAP amplitude (µV). | Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility outcome measure: recruitment rate measured using screening and randomisation logs. |  | Pre-screening / Identification, Recruitment and Consent, Baseline | 
| Feasibility outcome measure: participant retention rate measured using randomisation and withdrawal logs. |  | Recruitment and Consent, Baseline, Month 6 | 
| Feasibility outcome measure: adherence to treatment measured using Revitive App and a patient diary. |  | Month 6 | 
| Safety outcome measure: Adverse Events (AEs) collected and reported via AE form. |  | Baseline, Week 2, Month 6, Month 9 (and any communication in between) | 
| Safety outcome measure: Adverse Device Effects (ADEs) collected and reported via AE form. |  | Baseline, Week 2, Month 6, Month 9 (and any communication in between) | 
| Safety outcome measure: Serious Adverse Events (SAEs) collected and reported via SAE form. |  | Baseline, Week 2, Month 6, Month 9 (and any communication in between) | 
| Safety outcome measure: Serious Adverse Device Effects (SADEs) collected and reported via SAE form. |  | Baseline, Week 2, Month 6, Month 9 (and any communication in between) | 
| Secondary outcome measure: superficial peroneal nerve conductivity measured using a nerve conduction study. | Nerve conduction parameters include conduction velocity (m/s), calculated using distance and latency (ms), and SNAP amplitude (μV). | Month 6, Month 9 | 
| Secondary outcome measure: common peroneal nerve conductivity measured using a nerve conduction study. | Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms). | Month 6, Month 9 | 
| Secondary outcome measure: tibial nerve conductivity measured using a nerve conduction study. | Nerve conduction parameters include conduction velocity (m/s), calculated using distance and distal latency (ms), Compound Muscle Action Potential (CMAP) amplitude (mV) and minimum F wave latency (ms). | Month 6, Month 9 | 
| Secondary outcome measure: somatosensory nerve fibre function measured using Quantitative Sensory Testing (QST). | Somatosensory nerve fibre function will be assessed using the German Research Network on Neuropathic Pain (DFNS) QST protocol. The battery of tests includes measures of cold and warm detection thresholds, paradoxical heat sensations, cold and heat pain thresholds, mechanical detection threshold, mechanical pain threshold, mechanical pain sensitivity, dynamic mechanical allodynia, temporal pain summation, vibration detection threshold and pressure pain threshold. | Month 6, Month 9 | 
| Secondary outcome measure: mobility and balance measured using validated Berg Balance Scale (BBS). |  | Month 6, Month 9 | 
| Secondary outcome measure: quality of life measured using validated EQ-5D-5L questionnaire. |  | Month 6, Month 9 | 
| Secondary outcome measure: illness perceptions measured using validated Brief Illness Perception Questionnaire (Brief IPQ). |  | Month 6, Month 9 | 
| Secondary outcome measure: neuropathy signs and symptoms measured using validated screening questionnaire, Michigan Neuropathy Screening Instrument (MNSI). |  | Month 6, Month 9 | 
| Secondary outcome measure: neuropathy symptoms measured using validated Self-administered Neuropathy Total Symptom Score (NTSS-6-SA). |  | Month 6, Month 9 | 
| Secondary outcome measure: protected sensation measured using monofilament test. |  | Month 6, Month 9 | 
| Secondary outcome measure: neuropathic pain measured using Neuropathic Pain Symptom Inventory (NPSI). |  | Month 6, Month 9 | 
| Secondary outcome measure: daily pain measured using 11-point Numerical Rating Scale (NRS) collected via text message. |  | Daily for treatment phase (6 months) | 
| Secondary outcome measure: daily sleep interference measured using Daily Sleep Interference Scale (DSIS) (30) collected via text message. |  | Daily for treatment phase (6 months) | 
| Secondary outcome measure: peripheral arterial perfusion measured using Ankle Brachial Pressure Index (ABPI). |  | Baseline | 
| Secondary outcome measure: device sensation measured using device sensory threshold and suprathreshold. |  | Month 6, Month 9 | 
| Secondary outcome measure: device experience measured using device experience questionnaire. |  | Month 6 | 
| Secondary outcome measure: device credibility and expectancy measured using modified credibility and expectancy questionnaire. |  | Baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Neuromuscular electrical stimulation, Nerve conduction