Functional and Neuroprotective Effects of Restoring Lower Limb Sensation After Diabetic Peripheral Neuropathy

The purpose of this study is to evaluate the effectiveness of providing sensation of the missing limb to individuals with above and below the knee limb loss. The investigators will implanted stimulating electrodes to send small electrical currents to the remaining nerves. These small electrical currents cause the nerves to generate signals that are then transferred to your brain similar to how the information about your foot and lower limb used to be transferred to the brain prior to your limb loss. Additionally, there is the option to have muscle recording electrodes implanted within the muscles of the lower limb with the goal to develop a motor controller that would allow the user to have intuitive control of a robotic prosthetic leg.

Study Overview

• Status: Active, not recruiting
• Conditions: Diabetic Peripheral Neuropathy; Lower Extremity Amputee
• Intervention / Treatment: Device: Implanted Multi contact stimulating electrode and intramuscular electromyography recording electrode

Detailed Description

Electrodes are surgically implanted on one to four nerves of the residual limb. Intramuscular recording electrodes can be implanted in the lower limbs and hip muscles in order to obtain electromyography (EMG) signals. The EMG recordings will be used to develop an algorithm which can operate an advanced robotic prosthesis in which the prosthesis joint(s) movements could be controlled. An external wearable stimulation device controls the delivery of electrical pulses to the implanted system. An instrumented prosthesis will be developed such that perceived sensations would correspond to prosthesis interactions with the floor. The instrumented prosthesis will be worn while the participant is engaging in various functional tasks, such as standing, walking or climbing stairs or with visual or mental distractions.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-1702
      • Louis Stokes VA Medical Center, Cleveland, OH

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Veteran
• Chronic, medically stable lower limb amputation due to diabetes or insensate foot due to Diabetic peripheral neuropathy
• Being ambulatory and ability to stand or walk with prosthesis or orthosis
• Viable target nerves in the lower extremity as determined by standard-of-care clinical tests of nerve conduction, response to stimulation, sensory evoked potentials (SEP) and the like
• Good skin integrity and personal hygiene
• Absence of autoimmune deficiencies, seizure disorders or cardiac abnormalities contraindicating stimulation
• Sufficient social support and personal ability to tolerate study procedures and comply with follow-up schedule

Exclusion Criteria:

• Active pressure ulcers or chronic skin ulcerations
• Uncontrolled diabetes with HbA1c greater than or equal to 69 mmol/mol (8.5%)
• Significant vascular disease
• Significant history of poor wound healing
• Significant history of uncontrolled infections
• Active infection
• Significant pain in the foot, residual or phantom limb
• Pregnancy
• Inability to speak English: The study design requires the subject to communicate and describe the elicited sensations in their lower limb
• History of vestibular or movement disorders that would compromise balance or walking
• Class II or III obesity (Body Mass Index > 35)
• Uncontrolled depression, psychoses or cognitive impairments. Subjects with unstable mental illness or severe cognitive impairments may be unable to comply with a long term study schedule
• Expectation that MRI will be required at any point for the duration of study or while percutaneous leads are in place. At this time MRI is contraindicated, subjects who require regular MRI should not enroll
• Arthritis in the area of implant- Inflammation or stiffness in the area of implant could limit placement of the electrodes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Multi contact electrode implant and implanted electromyography recording electrodes; 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.

Device: Implanted Multi contact stimulating electrode and intramuscular electromyography recording electrode; See arm description; Other Names: Sensory Neuroprosthesis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stimulation thresholds	Quantify the minimum stimulation required to evoke electrically induced sensations on the phantom limb.	9 months post implant
Functional Gait Assessment (FGA)	The Functional Gait Assessment is a 10 task test that measures postural stability. Each task is scored from 0 -3 with 0 indicating severe impairment in the task and 3 indicating normal ambulation. The scores are combined to give a total score. The maximum score is 30. A higher score indicates a better outcome.	6 months post implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropathic Pain Syndrome Inventory (NPSI)	The NPSI is comprised of five subscales, each representing different dimensions of neuropathic pain: burning spontaneous pain (burning), pressing spontaneous pain (pressing), paroxysmal pain (paroxysmal), evoked pain (evoked), and paresthesia/dysesthesia Each area subscale is scored between 0-10. The scores are not combined, but are able to report on different aspects of neuropathic pain. A higher score indicates a worse outcome.	4 years post implant

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Collaborators: Case Western Reserve University
• Investigators: Principal Investigator: Ronald Triolo, PhD, Louis Stokes VA Medical Center, Cleveland, OH

Publications and helpful links

Helpful Links

• VA Center of Excellence website listing this and other ongoing studies.

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2021
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: November 20, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 8, 2020

Study Record Updates

• Last Update Posted (Actual): August 20, 2026
• Last Update Submitted That Met QC Criteria: August 19, 2026
• Last Verified: August 1, 2026

More Information

Terms related to this study

• Keywords: Limb Loss; Sensory Feedback; Prosthesis User
• Additional Relevant MeSH Terms: Endocrine System Diseases; Nervous System Diseases; Neuromuscular Diseases; Diabetes Mellitus; Diabetes Complications; Peripheral Nervous System Diseases; Diabetic Neuropathies
• Other Study ID Numbers: A3566-R; 1583890 (Other Identifier: IRBnet)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Deidentified data will be provided upon request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes