Agonist-Antagonist Myoneural Interface for Functional Limb Restoration After Transtibial Amputation

NCT03913273 | Completed Results

• 2 other identifiers: 1812634918R01HD097135
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

This study involves the functional testing of a new lower extremity prosthesis by healthy, active participants with fully healed transtibial (below knee) amputations. The study design calls for an experimental group of eleven participants who received two agonist-antagonist myoneural interfaces (AMIs) that were surgically constructed during a modified transtibial amputation procedure, and a control group of eleven matched participants who received standard transtibial amputations. The study protocol involves one or more of the following activities:

1. 1.Collection of electromyography (EMG) data from participants' lower limbs to characterize muscle activation and create maps specific to individual participants,
2. 2.Investigation of participants' capabilities to use a new lower extremity prosthesis that is designed to allow independent actuation of the ankle and subtalar joints, and offers EMG-modulated control over prosthetic joint position and stiffness, and
3. 3.Exploration of AMIs as a means of communicating information between the participant and the new prosthesis using an experimental system involving EMG, functional electrical stimulation, and ultrasound.

Conditions

Amputation

Keywords

Proprioception; Movement; Joint Prosthesis; Feedback; Rehabilitation

Outcome Measures

Primary Outcomes (4)

• Stability of Joint Position Control in Free Space

  The stability of joint position control in free space is quantified by the number of the distinct synergy activations (distinct movements) achieved out of a total of four targeted movements of interest: (1) ankle plantar flexion (toe down), (2) dorsiflexion (toe up), (3) subtalar joint eversion (sole of foot outward), and (4) subtalar joint inversion (sole of foot inward). For each movement, the subject is asked attempt the movement while the distinct synergy activation/neural signals are quantified using electromyography (EMG) data. An outcome of 4 indicates that the subject was able to produce distinct activations for each of the 4 targeted movements. An outcome of less than 4 indicates that although a subject attempted the movement, they were not able to successfully produce distinct activations for some portion of the targeted movements.

  1 time point, post-amputation

• Economy of Motion for Free Space Movements

  The economy of motion is computed as the total travel distance through synergy space, normalized by the minimum possible/most direct travel path, to reflect control efficiency. Given this definition, the economy of motion indicates the trajectory straightness of movements that were produced to achieve the target discrete movements. For this study, the movements were ankle plantar-dorsiflexion and subtalar inversion-eversion. An outcome of 100% represents how the two movements together could allow for an economy of the targeted movements in that space, indicating perfect economy of motion. The percentage may decrease if a subject achieves the targeted movements in a less efficient manner. For these movements, the economy of motion was evaluated under increasing time constraints from 2.0 s to 1.5 s, 1 s, 0.8 s, and 0.5 s.

  1 time point, post-amputation

• Late Swing Ankle Plantar Flexion During Stair Descent

  To address the clinical trial aim of determining whether AMIs can improve prosthetic terrain adaptations, we assessed swing phase control during stair descent by measuring the capability of the neuroprosthesis to exhibit prosthetic ankle joint plantar flexion characteristic of stair descent. This metric was defined as the change in ankle joint angle from terminal stance to terminal swing, capturing the user's ability to distinctly control joint angle transitions across gait phases of stair descent. For further details see: H. Song, T.-H. Hsieh, S. H. Yeon, T. Shu, M. Nawrot, C. F. Landis, G. N. Friedman, E. A. Israel, S. Gutierrez-Arango, M. J. Carty, L. E. Freed, H. M. Herr, Continuous neural control of a bionic limb restores biomimetic gait after amputation. Nat Med 30, 2010-2019 (2024).

  1 time point, post-amputation

• Late Swing Ankle Dorsiflexion During Stair Ascent

  To address the clinical trial aim of determining whether AMIs can improve prosthetic terrain adaptations, we assessed swing phase control during stair ascent by measuring the capability of the neuroprosthesis to exhibit prosthetic ankle joint dorsiflexion characteristic of stair ascent. This metric was defined as the change in ankle joint angle from terminal stance to terminal swing, capturing the user's ability to distinctly control joint angle transitions across gait phases of stair ascent. For further details see: H. Song, T.-H. Hsieh, S. H. Yeon, T. Shu, M. Nawrot, C. F. Landis, G. N. Friedman, E. A. Israel, S. Gutierrez-Arango, M. J. Carty, L. E. Freed, H. M. Herr, Continuous neural control of a bionic limb restores biomimetic gait after amputation. Nat Med 30, 2010-2019 (2024).

  1 time point, post-amputation

Secondary Outcomes (2)

• Correlation of Ankle Joint Proprioception

  1 time point, post-amputation

• Controllability Over Prosthetic Joint Dorsi and Plantar Flexion

  1 time point, post-amputation

Study Arms (2)

Intervention group

EXPERIMENTAL

Intervention: AMI transtibial amputation

Procedure: AMI transtibial amputation

Control group

ACTIVE COMPARATOR

Intervention: Standard transtibial amputation

Procedure: Standard transtibial amputation

Interventions

AMI transtibial amputation PROCEDURE

Two Agonist-antagonist myoneural interfaces (AMIs) were surgically constructed during a modified transtibial amputation procedure. Each AMI was made of natively innervated and vascularized muscle segments - an agonist and antagonist - that were surgically connected in series within the amputated residuum. Tarsal tunnels, including segments of each tunnel's native tendon component, were procured from the amputated joint. The tunnels were affixed to the residual limb tibia and the AMIs were constructed by coaptation of an agonist and an antagonist muscle to either end of the tendon passing through the tunnel. Consequently, the force produced by one muscle stretches its partner such that the AMI can communicate signals from the mechanoreceptors in both muscles to the central nervous system.

Intervention group

Standard transtibial amputation PROCEDURE

A standard transtibial amputation was performed according to traditional techniques. No surgical construction of agonist-antagonist myoneural interfaces (AMIs) was performed.

Control group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Experimental group participants:
• Modified transtibial (below knee) amputation incorporating agonist-antagonist myoneural interfaces (AMIs) and performed at the Brigham and Women's Hospital, Boston, MA.
• Fully healed amputation site
• Proficiency in using a standard lower extremity prosthesis
• Activity or K-Level of at least K3 to K4 (capability to ambulate with variable cadence)
• Control group participants:
• Standard transtibial (below knee) amputation
• Fully healed amputation site
• Proficiency in using a standard lower extremity prosthesis
• Activity or K-Level of at least K3 to K4 (capability to ambulate with variable cadence)

You may not qualify if:

• Experimental and Control group participants:
• Persons beyond the stated age restrictions
• Persons with one or more of the following underlying health conditions: cardiopulmonary instability manifest as coronary artery disease, chronic obstructive pulmonary disease, and extensive microvascular compromise
• Persons who are active smokers
• Persons who are pregnant

Sponsors & Collaborators

• Massachusetts Institute of Technology: lead
• National Institutes of Health (NIH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Massachusetts Institute of Technology

Cambridge, Massachusetts, 02139, United States

Location

Related Publications (14)

• Srinivasan SS, Carty MJ, Calvaresi PW, Clites TR, Maimon BE, Taylor CR, Zorzos AN, Herr H. On prosthetic control: A regenerative agonist-antagonist myoneural interface. Sci Robot. 2017 May 31;2(6):eaan2971. doi: 10.1126/scirobotics.aan2971.

  PMID: 33157872 BACKGROUND

• Clites TR, Carty MJ, Ullauri JB, Carney ME, Mooney LM, Duval JF, Srinivasan SS, Herr HM. Proprioception from a neurally controlled lower-extremity prosthesis. Sci Transl Med. 2018 May 30;10(443):eaap8373. doi: 10.1126/scitranslmed.aap8373.

  PMID: 29848665 BACKGROUND

• Clites TR, Herr HM, Srinivasan SS, Zorzos AN, Carty MJ. The Ewing Amputation: The First Human Implementation of the Agonist-Antagonist Myoneural Interface. Plast Reconstr Surg Glob Open. 2018 Nov 16;6(11):e1997. doi: 10.1097/GOX.0000000000001997. eCollection 2018 Nov.

  PMID: 30881798 BACKGROUND

• Amtmann D, Morgan SJ, Kim J, Hafner BJ. Health-related profiles of people with lower limb loss. Arch Phys Med Rehabil. 2015 Aug;96(8):1474-83. doi: 10.1016/j.apmr.2015.03.024. Epub 2015 Apr 25.

  PMID: 25917819 BACKGROUND

• Kurichi JE, Vogel WB, Kwong PL, Xie D, Bates BE, Stineman MG. Factors associated with total inpatient costs and length of stay during surgical hospitalization among veterans who underwent lower extremity amputation. Am J Phys Med Rehabil. 2013 Mar;92(3):203-14. doi: 10.1097/PHM.0b013e31827446eb.

  PMID: 23117271 BACKGROUND

• Ziegler-Graham K, MacKenzie EJ, Ephraim PL, Travison TG, Brookmeyer R. Estimating the prevalence of limb loss in the United States: 2005 to 2050. Arch Phys Med Rehabil. 2008 Mar;89(3):422-9. doi: 10.1016/j.apmr.2007.11.005.

  PMID: 18295618 BACKGROUND

• Herr HM, Grabowski AM. Bionic ankle-foot prosthesis normalizes walking gait for persons with leg amputation. Proc Biol Sci. 2012 Feb 7;279(1728):457-64. doi: 10.1098/rspb.2011.1194. Epub 2011 Jul 13.

  PMID: 21752817 BACKGROUND

• Stolyarov R, Burnett G, Herr H. Translational Motion Tracking of Leg Joints for Enhanced Prediction of Walking Tasks. IEEE Trans Biomed Eng. 2018 Apr;65(4):763-769. doi: 10.1109/TBME.2017.2718528. Epub 2017 Jun 22.

  PMID: 28650802 BACKGROUND

• Huang S, Huang H. Voluntary Control of Residual Antagonistic Muscles in Transtibial Amputees: Reciprocal Activation, Coactivation, and Implications for Direct Neural Control of Powered Lower Limb Prostheses. IEEE Trans Neural Syst Rehabil Eng. 2019 Jan;27(1):85-95. doi: 10.1109/TNSRE.2018.2885641. Epub 2018 Dec 7.

  PMID: 30530332 BACKGROUND

• Hargrove LJ, Simon AM, Young AJ, Lipschutz RD, Finucane SB, Smith DG, Kuiken TA. Robotic leg control with EMG decoding in an amputee with nerve transfers. N Engl J Med. 2013 Sep 26;369(13):1237-42. doi: 10.1056/NEJMoa1300126.

  PMID: 24066744 BACKGROUND

• Irwin ZT, Schroeder KE, Vu PP, Tat DM, Bullard AJ, Woo SL, Sando IC, Urbanchek MG, Cederna PS, Chestek CA. Chronic recording of hand prosthesis control signals via a regenerative peripheral nerve interface in a rhesus macaque. J Neural Eng. 2016 Aug;13(4):046007. doi: 10.1088/1741-2560/13/4/046007. Epub 2016 Jun 1.

  PMID: 27247270 BACKGROUND

• Ortiz-Catalan M, Hakansson B, Branemark R. An osseointegrated human-machine gateway for long-term sensory feedback and motor control of artificial limbs. Sci Transl Med. 2014 Oct 8;6(257):257re6. doi: 10.1126/scitranslmed.3008933.

  PMID: 25298322 BACKGROUND

• Schiefer M, Tan D, Sidek SM, Tyler DJ. Sensory feedback by peripheral nerve stimulation improves task performance in individuals with upper limb loss using a myoelectric prosthesis. J Neural Eng. 2016 Feb;13(1):016001. doi: 10.1088/1741-2560/13/1/016001. Epub 2015 Dec 8.

  PMID: 26643802 BACKGROUND

• Srinivasan SS, Gutierrez-Arango S, Teng AC, Israel E, Song H, Bailey ZK, Carty MJ, Freed LE, Herr HM. Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation. Proc Natl Acad Sci U S A. 2021 Mar 2;118(9):e2019555118. doi: 10.1073/pnas.2019555118.

  PMID: 33593940 DERIVED

Related Links

• STAT Documentary on the "Ewing" amputation surgery
• Brigham and Women's hospital video on the "Ewing" amputation surgery

Limitations and Caveats

We were not able to measure the outcome metric entitled, "Subtalar Eversion for an Obstacle". This measurement requires a functional robotic subtalar joint. During testing, our powered prosthesis malfunctioned such that we were not able to fully actuate the robotic subtalar joint. Hence, a measurement of subtalar eversion onto a ground block was not achieved.

Results Point of Contact

• Title: Hugh Herr, PI of clinical trial
• Organization: MIT

hherr@media.mit.edu

6173143661

Study Officials

• Hugh M Herr, PhD

  Massachusetts Institute of Technology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study calls for an experimental group of eleven participants who underwent AMI transtibial amputations incorporating surgically constructed Agonist-antagonist Myoneural Interfaces (AMIs), and a control group of eleven participants who underwent standard transtibial amputations. Each participant in the control group is prospectively matched to a participant in the experimental group to the degree possible based on time since amputation, body habitus, age, and biological sex. Matching is conducted by methods that estimate causal effects by reducing imbalance in the matching variables; any differences in outcomes in the two groups should therefore be attributable to the AMIs. We anticipate that a planned number of thirty two enrolled, consented participants will allow us to account for participant attrition over time. The study protocol focuses on functional performance testing of a multi-degree of freedom prosthesis in fully healed participants.

Study Record Dates

• First Submitted: April 11, 2019
• First Posted: April 12, 2019
• Study Start: June 12, 2019
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2025
• Last Updated: February 17, 2026
• Results First Posted: February 17, 2026

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)