Neuromuscular Electrical Stimulation For The Treatment of Diabetic Peripheral Neuropathy (NMES for DPN)

• ClinicalTrials.gov Identifier: NCT03767478
• Recruitment Status: Recruiting
• First Posted: December 6, 2018
• Last Update Posted: January 4, 2022
• Sponsor: Imperial College London
• Collaborator: Actegy Ltd.
• Information provided by (Responsible Party): Imperial College London

Study Description

Brief Summary:

Diabetic peripheral neuropathy (DPN) 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's neuroarthropathy, which are risk factors for lower limb amputation and mortality. In the United Kingdom, the annual costs of DPN alone exceed £300 million, with further complications expected to cost an additional £1 billion. Currently, management strategies for DPN focus on prophylaxis and pain management. Neuromuscular electrical stimulation (NMES) is a novel nonpharmacological intervention for people with DPN. NMES is the application of electrical impulses which are of sufficiency intensity to improve artificial contraction of the muscle tissue and may help with DPN by improving microvascular blood flow and nerve conductivity by direct stimulation of the nerves.

Condition or disease	Intervention/treatment	Phase
Diabetic Peripheral Neuropathy; Diabetic Neuropathies; Diabetic Polyneuropathy; Diabetic Complication	Device: Revitive Medic Coach (Actegy Ltd); Device: Sham Revitive Medic Coach (Actegy Ltd)	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 190 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Neuromuscular Electrical Stimulation For The Treatment of Diabetic Peripheral Neuropathy: A Multi-centre, Double-blinded, Randomised Controlled Trial (NMES for DPN)
• Actual Study Start Date: January 27, 2018
• Estimated Primary Completion Date: May 31, 2023
• Estimated Study Completion Date: December 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Sham Comparator: Control group; Best Medical Therapy + Sham Revitive Medic Coach Neuromuscular Electrical Stimulation Device for 6 months	Device: Sham Revitive Medic Coach (Actegy Ltd); 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).; Other Name: Sham Footplate Neuromuscular Electrical Stimulation Device
Active Comparator: Intervention group; Best Medical Therapy + Revitive Medic Coach Neuromuscular Electrical Stimulation Device for 6 months	Device: Revitive Medic Coach (Actegy Ltd); 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).; Other Name: Footplate Neuromuscular Electrical Stimulation Device

Outcome Measures

Primary Outcome Measures :

1. Any improvement in nerve conduction parameters of the tested sural, common peroneal, tibial and superficial peroneal nerves measured using a nerve conduction study. [ Time Frame: Month 6 ]

   Multi-component, single outcome. Nerve conduction parameters include:

   • Sural: conduction velocity (m/s) - calculated using distance and latency, SNAP amplitude (µV)
   • Common peroneal: conduction velocity (m/s) - calculated using distance and latency, CMAP amplitude (mV), minimum F wave latency (ms)
   • Tibial: conduction velocity (m/s) - calculated using distance and latency, CMAP amplitude (mV), minimum F wave latency (ms)
   • Superficial peroneal: conduction velocity (m/s) - calculated using distance and latency, SNAP amplitude (µV)

Secondary Outcome Measures :

1. Mobility and balance [ Time Frame: Month 6, Month 9 ]
   Berg Balance Scale Questionnaire is a 14-item disease specific questionnaire (scoring up to 56) assessing elements of balance, with each element scoring 0-4.
2. Quality of life - EuroQol 5 Domain Quality of Life Questionnaire [ Time Frame: Month 6, Month 9 ]
   EuroQol 5 Domain Quality of Life (EQ-5D QOL) questionnaire will provide assessment of the participants quality of life (EQ-5D QOL from 0-1).
3. Diabetic neuropathy [ Time Frame: Month 6, Month 9 ]
   Michigan Neuropathy Screening Instrument is a patient (15 questions) and clinician (5 questions) completed questionnaire that allows assessment of neuropathy.
4. Neuropathy symptoms [ Time Frame: Month 6, Month 9 ]
   NTSS-6 Questionnaire is a 6 item questionnaire, scoring a maximum of 3.66 per item with a maximum score of 21.96. This grades neuropathy symptomatology.
5. Protected sensation [ Time Frame: Month 6, Month 9 ]
   Monofilament test is an objective measurement to assess loss of protective sensation. The 10g monofilament will be perpendicularly applied to five sites (1st, 3rd, and 5th metatarsal heads and plantar surface of the hallux and 3rd toe) of both feet, scoring a maximum of 10.
6. Pain [ Time Frame: Daily for treatment phase (6 months) ]
   Daily pain measured using 11-point Numerical Rating Scale (NRS) collected via text message.
7. Sleep interference [ Time Frame: Daily for treatment phase (6 months) ]
   Daily Sleep Interference Scale (DSIS) is a 11-point scale collected via text message.
8. Cramping [ Time Frame: Daily for treatment phase (6 months) ]
   Daily cramp duration and severity measured using a questionnaire and 11-point Numerical Rating Scale (NRS) collected via text message.
9. Any improvement in nerve conduction parameters of the tested sural, common peroneal, tibial and superficial peroneal nerves measured using a nerve conduction study. [ Time Frame: Month 9 ]

   Multi-component, single outcome. Nerve conduction parameters include:

   • Sural: conduction velocity (m/s) - calculated using distance and latency, SNAP amplitude (µV)
   • Common peroneal: conduction velocity (m/s) - calculated using distance and latency, CMAP amplitude (mV), minimum F wave latency (ms)
   • Tibial: conduction velocity (m/s) - calculated using distance and latency, CMAP amplitude (mV), minimum F wave latency (ms)
   • Superficial peroneal: conduction velocity (m/s) - calculated using distance and latency, SNAP amplitude (µV)
10. Neuromuscular electrical stimulation (NMES) sensation - Intervention group only [ Time Frame: Month 6, Month 9 ]
    Assessed using sensory threshold and suprathresholds of NMES device.
11. Arterial Blood Flow [ Time Frame: Month 6, Month 9 ]
    Arterial blood flow assessed by Duplex Ultrasound (DU), utilising standard haemodynamics assessment, and ankle brachial pressure index.
12. Microcirculation [ Time Frame: Month 6, Month 9 ]
    Microcirculation assessed by Laser Doppler Flowmetry (LDF).
13. Skin oxygenation [ Time Frame: Month 6, Month 9 ]
    Skin oxygenation assessed by Trancutaenous Pressure of Oxygen (TcPO2).
14. Device experience [ Time Frame: Month 6 ]
    Measured using simple questionnaire.
15. Compliance with treatment allocations [ Time Frame: Month 6 ]
    Measured using Revitive App and patient diary.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

INCLUSION CRITERIA

• Aged 18+
• Diagnosis of Type 1 or Type 2 diabetes mellitus and receiving best medical therapy
• Diagnosis of diabetic peripheral neuropathy based on: a validated screening questionnaire Michigan Neuropathy Screening Instrument questionnaire score of ≥ 7 and nerve conduction study of at least one lower limb meet the criteria for mild, moderate or severe DPN based on both sural and common peroneal testing
• Has access to internet at home to use the Revitive App

EXCLUSION CRITERIA

• Lacks capacity to provide informed consent
• Pregnant
• Has an implanted electronic, cardiac or defibrillator device
• Has other cause of peripheral neuropathy (e.g. excessive drinking, low levels of vitamin B12 or other vitamins, syphilis, HIV, underactive thyroid gland)
• Has current foot ulceration
• Has severe vascular disease requiring invasive intervention
• Being treated for, or have the symptoms of, an existing Deep Vein Thrombosis (DVT)
• Already using a neuromuscular electrical stimulation device

Contacts and Locations

Contacts

Contact: Tristan R A Lane, MBBS BSc FRCS PhD; 02033117317; tristan.lane@imperial.ac.uk

Contact: Sasha K Smith, BSc; sasha.smith@imperial.ac.uk

Locations

United Kingdom

Imperial College London; Recruiting

London, United Kingdom, W6 8RF

Contact: Tristan R Lane, PhD FRCS tristan.lane@imperial.ac.uk

Contact: Sasha Smith, BSc sasha.smith@imperial.ac.uk

Sponsors and Collaborators

Imperial College London

Actegy Ltd.

Investigators

• Study Chair: Alun H Davies, MA DM DSC FRCS FEBVS; Imperial College London

More Information

• Responsible Party: Imperial College London
• ClinicalTrials.gov Identifier: NCT03767478
• Other Study ID Numbers: 18HH4610; IRAS ID ( Other Identifier: 23712 ); NRES REC ID ( Other Identifier: 18/NE/0281 )
• First Posted: December 6, 2018
• Last Update Posted: January 4, 2022
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Available on request.
• Supporting Materials: Study Protocol

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

Neuromuscular electrical stimulation; Nerve conduction

Additional relevant MeSH terms:

Peripheral Nervous System Diseases; Diabetic Neuropathies; Polyneuropathies; Diabetes Complications; Neuromuscular Diseases; Nervous System Diseases; Diabetes Mellitus; Endocrine System Diseases