Nerve Stimulation for Diabetic Neuropathy

Overseen by Ronald Triolo, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: VA Office of Research and Development

Disqualifiers: Uncontrolled diabetes, Vascular disease, Infections, Obesity, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial aims to help people who have lost a leg by using small devices that send electrical signals to nerves and record muscle activity. These signals help the brain feel sensations from the missing limb, and the muscle data helps control a robotic leg more naturally.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Implanted Multi contact stimulating electrode and intramuscular electromyography recording electrode for diabetic neuropathy?

Research on similar electrode implants shows they can reliably stimulate and record nerve activity, which may help restore motor and sensory functions. Studies in animals demonstrate that these implants can evoke muscle responses and maintain stable nerve recordings over time, suggesting potential benefits for conditions like diabetic neuropathy. ^{1 2 3 4 5}

Is nerve stimulation for diabetic neuropathy generally safe in humans?

Research on similar nerve stimulation devices shows they are generally safe, with studies indicating stable and biocompatible interfaces in both animal and human models. Some studies noted expected mild inflammatory responses, but no significant harmful effects were reported. ^{6 7 8 9 10}

How does the implanted multi-contact stimulating electrode treatment for diabetic neuropathy differ from other treatments?

This treatment is unique because it involves implanting electrodes directly into the body to stimulate nerves and record muscle activity, which can provide more precise control and feedback compared to traditional treatments that do not use implanted devices. It offers a novel approach by potentially restoring sensory and motor functions through direct nerve stimulation and recording, which is not typically available in standard diabetic neuropathy treatments. ^{3 4 9 11 12}

Research Team

Ronald Triolo, PhD

Principal Investigator

Louis Stokes VA Medical Center, Cleveland, OH

Eligibility Criteria

This trial is for individuals with lower limb loss above or below the knee due to diabetes, who can walk or stand with assistance and have healthy nerves in their remaining limbs. They should have good skin health, no autoimmune issues, seizures, heart problems, and must be able to follow the study plan. Excluded are those with uncontrolled diabetes (HbA1c ≥ 8.5%), active skin ulcers, pregnancy, language barriers (non-English speakers), balance disorders, severe obesity (BMI > 35), mental health issues that affect study participation.

Inclusion Criteria

I can walk or stand using a prosthesis or brace.

I have a stable lower limb amputation or insensate foot due to diabetes.

I do not have autoimmune deficiencies, seizures, or heart problems that prevent stimulation treatments.

Exclusion Criteria

I have arthritis near where a medical device was implanted.

You have severe mental illness or problems with memory and thinking that may make it hard for you to follow the study schedule.

You expect to need MRI scans during the study, or you have a type of medical device that makes MRI scans unsafe for you.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgical Implantation

Electrodes are surgically implanted on one to four nerves of the residual limb and intramuscular recording electrodes can be implanted in the lower limbs and hip muscles.

1-2 weeks

Treatment

Participants receive stimulation through implanted electrodes to restore sensation and develop a motor controller for a robotic prosthetic leg.

9 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of neuropathic pain and functional gait.

4 years

Treatment Details

Interventions

• Implanted Multi contact stimulating electrode and intramuscular electromyography recording electrode (Neurostimulation Device)
• Multi contact electrode implant (Neurostimulation Device)

Trial Overview The trial tests implanted electrodes that provide sensation to nerves in the residual limb of amputees simulating natural feedback from a lost foot or leg. Additionally offered is an option for muscle recording electrodes aimed at creating intuitive control over robotic prosthetic legs through a motor controller.

Participant Groups

Group I: Multi contact electrode implant and implanted electromyography recording electrodes Experimental Treatment 1 Intervention

Fifteen subjects with lower limb amputation will receive implanted multicontact stimulating nerve cuff electrodes connected to temporary percutaneous leads. During experimental testing, a small amount of stimulation will be applied to the nerves through the contacts of the multichannel cuff electrode.

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Dr. Grant Huang

VA Office of Research and Development

Acting Chief Research and Development Officer

PhD in Medical Psychology and Master of Public Health from the Uniformed Services University of Health Sciences

Dr. Erica M. Scavella

VA Office of Research and Development

Chief Medical Officer since 2022

MD from University of Massachusetts School of Medicine

Findings from Research

The implantable intraorbitary device (IOD) allows for chronic delivery of solutions, recording of nerve activity, and electrical stimulation, demonstrating its multifunctional capabilities for peripheral nerve applications.

The device was successfully tested on the abducens nerve, showing that it can provide valuable electrophysiological data and deliver pharmacological substances, which could enhance research and treatment options for nerve-related conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A chronically implantable device for the controlled delivery of substances, and stimulation and recording of activity in severed nerves. Davis-López de Carrizosa, MA., Tena, JJ., Benítez-Temiño, B., et al.[2007]

A new multielectrode array has been developed for precise electrical stimulation of peripheral nerves, featuring twelve platinum electrodes designed to selectively stimulate individual nerve fibers in rats.

Sensitivity tests showed that the number of activated motor units increases cubically with the current amplitude, while selectivity is maximized when electrodes are spaced 200-250 microns apart, providing important insights for future device designs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sensitivity and selectivity of intraneural stimulation using a silicon electrode array. Rutten, WL., van Wier, HJ., Put, JH.[2013]

Microchannel electrode implants successfully recorded neural activity from regenerating sciatic nerves in freely moving rats over a three-month period, demonstrating their potential for long-term monitoring of nerve regeneration.

Histological analysis showed robust regeneration of mini-nerves within the implants, and the recorded neural firing patterns correlated with different phases of gait, indicating the implants' effectiveness in interfacing with nerve activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait. Musick, KM., Rigosa, J., Narasimhan, S., et al.[2018]

The novel thin-film multichannel electrode, designed for both recording and stimulating muscle activity, was successfully tested in six tremor patients and three healthy individuals, demonstrating its potential for applications in neuroprosthetics.

In one tremor patient, closed-loop stimulation using the electrode led to a significant reduction in tremor power by over 50%, indicating its efficacy in managing tremor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications. Muceli, S., Poppendieck, W., Hoffmann, KP., et al.[2020]

The study assessed the biocompatibility of the transverse intrafascicular multi-channel electrode (TIME) by implanting it in the median nerves of Göttingen minipigs for 33-38 days, showing no significant inflammatory response or necrosis, indicating good safety.

The presence of only a layer of fibrosis around the implant suggests that the TIME could be a promising neural interface for future use in neuroprostheses, as it demonstrates favorable biosafety characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biosafety assessment of an intra-neural electrode (TIME) following sub-chronic implantation in the median nerve of Göttingen minipigs. Kundu, A., Wirenfeldt, M., Harreby, KR., et al.[2017]

In a study of 216 patients with refractory painful diabetic neuropathy, 10 kHz spinal cord stimulation (SCS) led to a remarkable 79.9% reduction in pain over 24 months, with 90.1% of participants achieving at least 50% pain relief.

The treatment also significantly improved health-related quality of life and sleep, with 65.7% of participants showing clinically meaningful neurological improvements, indicating that 10 kHz SCS is both safe and effective for long-term management of this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial. Petersen, EA., Stauss, TG., Scowcroft, JA., et al.[2023]

This review outlines a comprehensive framework for translating neural interfaces for electrical modulation of the peripheral nervous system (PNS) from design to clinical use, emphasizing the importance of following FDA guidelines for safety and efficacy.

Key steps in the translational process include quantitative human anatomy, neural modeling, acute testing, and chronic deployment, with case studies demonstrating successful applications of specific electrode designs like the spiral cuff and Flat Interface Nerve Electrode (FINE).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A translational framework for peripheral nerve stimulating electrodes: Reviewing the journey from concept to clinic. Charkhkar, H., Christie, BP., Pinault, GJ., et al.[2021]

The four-contact spiral nerve-cuff electrodes demonstrated stable performance over 63 weeks, with a low stimulation charge threshold (mean 23.3 nC), indicating a reliable interface with the peripheral nervous system.

These electrodes were able to selectively stimulate different heads of the quadriceps muscle, achieving maximum twitch responses of 3.8 to 8.1 N m, which suggests their potential effectiveness for neuroprosthetic applications in individuals with spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve. Fisher, LE., Tyler, DJ., Anderson, JS., et al.[2021]

The Utah Slanted Electrode Array (USEA) was implanted in human median and ulnar nerves for four weeks, showing that the current design only penetrates a small percentage of the nerve tissue, which may limit its effectiveness.

Despite some inflammatory response observed around the electrodes, the USEA was still able to successfully record nerve signals and elicit sensory responses, indicating its potential for neuroprosthetic applications, but future designs should aim for better tissue integration and reduced inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays. Christensen, MB., Wark, HA., Hutchinson, DT.[2016]

A novel neural prosthesis design eliminates the need for an implanted stimulator by using surface electrodes to stimulate nerves through an insulated lead, allowing for effective nerve activation with minimal current.

The system demonstrated long-term stability in chronic implants for over 8 months, successfully producing graded muscle force without reaching contraction thresholds, indicating its potential for practical applications in restoring motor functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new means of transcutaneous coupling for neural prostheses. Gan, LS., Prochazka, A., Bornes, TD., et al.[2019]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

A chronically implantable device for the controlled delivery of substances, and stimulation and recording of activity in severed nerves. [2007]

2. United States pubmed.ncbi.nlm.nih.gov

Sensitivity and selectivity of intraneural stimulation using a silicon electrode array. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

A multielectrode array for intrafascicular recording and stimulation in sciatic nerve of cats. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Chronic multichannel neural recordings from soft regenerative microchannel electrodes during gait. [2018]

5. England pubmed.ncbi.nlm.nih.gov

A thin-film multichannel electrode for muscle recording and stimulation in neuroprosthetics applications. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Biosafety assessment of an intra-neural electrode (TIME) following sub-chronic implantation in the median nerve of Göttingen minipigs. [2017]

7. Ireland pubmed.ncbi.nlm.nih.gov

Long-term efficacy of high-frequency (10 kHz) spinal cord stimulation for the treatment of painful diabetic neuropathy: 24-Month results of a randomized controlled trial. [2023]

8. Netherlands pubmed.ncbi.nlm.nih.gov

A translational framework for peripheral nerve stimulating electrodes: Reviewing the journey from concept to clinic. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Chronic stability and selectivity of four-contact spiral nerve-cuff electrodes in stimulating the human femoral nerve. [2021]

10. Netherlands pubmed.ncbi.nlm.nih.gov

A histological analysis of human median and ulnar nerves following implantation of Utah slanted electrode arrays. [2016]

11. England pubmed.ncbi.nlm.nih.gov

Micro-channel sieve electrode for concurrent bidirectional peripheral nerve interface. Part B: stimulation. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

A new means of transcutaneous coupling for neural prostheses. [2019]