NCT03913273

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

Completed NA Results posted Last updated 17 February 2026

What this trial tests

NA trial testing AMI transtibial amputation in Amputation in 14 participants. Completed in 1 June 2025.

Timeline

12 June 2019

Primary endpoint
1 June 2025

1 June 2025

Quick facts

Lead sponsor	Massachusetts Institute of Technology
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	basic science
Enrollment	14
Start date	12 June 2019
Primary completion	1 June 2025
Estimated completion	1 June 2025
Sites	1 location across United States

Drugs / interventions tested

• AMI transtibial amputation
• Standard transtibial amputation

Conditions studied

• Amputation — all drugs for Amputation →

Sponsor

Massachusetts Institute of Technology

Who can join

Adults 18 to 65, any sex, with Amputation. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Stability of Joint Position Control in Free Space Primary · 1 time point, post-amputation

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 prod

Group	Value	95% CI
Intervention Group	4	± 0
Control Group	3.1	± 0.7

Economy of Motion for Free Space Movements Primary · 1 time point, post-amputation

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

2 second Constraint

Group	Value	95% CI
Intervention Group	72.42	± 3.55
Control Group	69.38	± 4.09

1.5 second Constraint

Group	Value	95% CI
Intervention Group	73.03	± 5.18
Control Group	70.29	± 3.75

1 second Constraint

Group	Value	95% CI
Intervention Group	73.29	± 3.95
Control Group	69.02	± 2.85

0.8 second Constraint

Group	Value	95% CI
Intervention Group	72.67	± 2.70
Control Group	69.18	± 2.81

0.5 second Constraint

Group	Value	95% CI
Intervention Group	71.88	± 3.95
Control Group	66.96	± 2.87

Late Swing Ankle Plantar Flexion During Stair Descent Primary · 1 time point, post-amputation

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

Group	Value	95% CI
Intervention Group	-15.65	± 6.82
Control Group	-6.27	± 4.36

Late Swing Ankle Dorsiflexion During Stair Ascent Primary · 1 time point, post-amputation

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. Frie

Group	Value	95% CI
Intervention Group	19.27	± 3.51
Control Group	4.05	± 5.54

Correlation of Ankle Joint Proprioception Secondary · 1 time point, post-amputation

Correlation of Ankle Joint Proprioception was measured by applying functional electrical stimulation (FES) to either the tibialis anterior (TA) or lateral gastrocnemius (LG) and instructing the subject to resist the experienced movement. The level of correlation (R2) for both dorsiflexion and plantarflexion between the applied stimulation current and the subjects perceived joint counter-torque for the intervention subjects was compared to control subjects.

Dorsiflexion

Group	Value	95% CI
Intervention Group	0.77	0.58 – 0.95
Control Group	0.41	0.06 – 0.76

Plantar Flexion

Group	Value	95% CI
Intervention Group	0.82	0.67 – 0.97
Control Group	0.5	0.17 – 0.82

Controllability Over Prosthetic Joint Dorsi and Plantar Flexion Secondary · 1 time point, post-amputation

We analyzed the correlation (R2) between agonist contraction and antagonist stretch during dorsi and plantar flexion movements. Muscle fascicle strains were estimated from ultrasound data recorded from the agonist and antagonist muscles (e.g. lateral gastrocnemius (LG) and tibialis anterior (TA) during plantar flexion). Fascicle measurements were generated via optical tracking software. In the AMI subjects, because of the mechanical coupling of the agonist and antagonist muscles within the residual limb, a volitional contraction of the agonist muscle inherently induces a passive stretch in th

Dorsiflexion

Group	Value	95% CI
Intervention Group	0.41	0.06 – 0.76
Control Group	0.14	-0.15 – 0.43

Plantar Flexion

Group	Value	95% CI
Intervention Group	0.24	-0.1 – 0.58
Control Group	0.15	-0.15 – 0.42

Sponsor's own description

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. Collection of electromyography (EMG) data from participants' lower limbs to characterize muscle activation and create maps specific to individual participants,
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. 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.

The hypothesis is that transtibial amputations involving AMIs can offer improved motor control of the new prosthesis while also enabling proprioceptive sensation (perception of the position, movement, and torque of the affected limb and prosthetic joint). The AMIs are expected to improve voluntary prosthetic control, improve prosthetic terrain adaptations, and offer new possibilities for bi-directional communication across the human-device interface.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Continuous neural control of a bionic limb restores biomimetic gait after amputation.
   Song H, Hsieh TH, Yeon SH, Shu T, et al · · 2024 · cited 36× · PMID 38951635 · DOI 10.1038/s41591-024-02994-9
2. Neural interfacing architecture enables enhanced motor control and residual limb functionality postamputation.
   Srinivasan SS, Gutierrez-Arango S, Teng AC, Israel E, et al · · 2021 · cited 16× · PMID 33593940 · DOI 10.1073/pnas.2019555118
3. Agonist-antagonist muscle strain in the residual limb preserves motor control and perception after amputation.
   Song H, Israel EA, Gutierrez-Arango S, Teng AC, et al · · 2022 · cited 9× · PMID 35942078 · DOI 10.1038/s43856-022-00162-z