Imaging of 3D Innervation Zone Distribution in Spastic Muscles From High-density Surface EMG Recordings

Imaging of 3D Innervation Zone Distribution in Spastic Muscles From High-density Surface

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03302741

Enrollment

Registered

2017-10-05

Start date

2017-11-21

Completion date

2019-11-18

Last updated

2020-11-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Spasticity

Keywords

stroke

Brief summary

The purpose of this study is to evaluate if it is possible to use a new 3D imaging method to guide Botulinum neurotoxin (BTX) injection for muscle spasticity management after stroke. This imaging method is called three dimensional innervation zone imaging, or 3DIZI.

Interventions

DRUGBotulinum neurotoxin (BTX)

Each patient will receive BTX injections in 2 sites. 100 units at double dilution will be injected at each site.

OTHERPhysical Therapy

Standard physical therapy will be ordered to both groups as part of standard of care for patients after BTX injections to maximize the outcomes.

DEVICEStandard BTX injection (ultrasound guided)

For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the innervation zones (IZs) of the entire muscle.

DEVICE3-dimensional innervation zone (3DIZ) guided injection

Simultaneous surface EMG and intramuscular EMG measurements will be acquired from the spastic biceps of the patients. Patients will be seated comfortably on a height-adjustable chair. The arm to be tested will be secured firmly on a customized apparatus with the elbow joint at approximately 90° of flexion and the shoulder at approximately 45° of abduction and 30° of flexion. The 128-channel unipolar surface EMG signals will be recorded with 2 flexible 2-dimensional 64-channel surface electrode array. A coating fine wire electrode will be inserted into the mid-axial section of the biceps to record bipolar intramuscular EMG signals. Ultrasound scan will be performed on the biceps to identify the location of the inserted wire electrode. Patients will be asked to contract their impaired biceps to perform maximum voluntary contraction of elbow flexion against the vertical plates 3 times.

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

SINGLE (Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 75 Years

Healthy volunteers

Inclusion criteria

* a history of not more than one stroke which occurred at least 6 months prior to study enrollment; * elbow flexor spasticity rated at 2 or 3 on Modified Ashworth scale (MAS); * receiving repeated botulinum toxin injection every 3-4 months; * absence of excessive pain in the paretic upper limb; * capacity to provide informed consent, with Mini-Mental State Examination (MMSE) must be 25 or higher; The following modified Ashworth scale (MAS) will be used for spasticity assessment: 0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.

Exclusion criteria

* recent botulinum toxin injection \< 4 months; * recent changes in antispastic medications \<3 weeks (i.e., the antispastic medication regime is not stable; * Changes in antispastic medications (such as baclofen, tizanidine, dantrolene etc) during the followup research visits. (NOTE: it is clinically rare for patients who receive repeated injections to change their antispastic medications); * history of spinal cord injury or traumatic brain damage; * history of serious medical illness such as cardiovascular or pulmonary complications; * any condition that, in the judgment of a physician, would prevent the person from participating.

Design outcomes

Primary

Measure	Time frame	Description
Spasticity as Assessed by Reflex Torque of Elbow Flexors	baseline (1 day prior to BTX injection)	Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.

Secondary

Measure	Time frame	Description
Spasticity as Assessed by the Modified Ashworth Scale (MAS)	baseline (1 day prior to BTX injection)	The following modified Ashworth scale (MAS) will be used for spasticity assessment: 0 -No increase in muscle tone; 1 -Slight increase in muscle tone, manifested by a catch and release or by minimal resistance at the end of the range of motion when the affected part(s) is moved in flexion or extension; 1+ -Slight increase in muscle tone, manifested by a catch, followed by minimal resistance throughout the remainder (less than half) of the ROM; 2 -More marked increase in muscle tone through most of the ROM, but affected part(s) easily moved; 3 -Considerable increase in muscle tone, passive movement difficult; 4 -Affected part(s) rigid in flexion or extension.

Countries

United States

Participant flow

Participants by arm

Arm	Count
Standard BTX Injection (Ultrasound Guided) For standard injection procedures, target muscles will be visualized under ultrasound imaging which is operated by an experienced and dedicated technician. Position of needle tip within the target muscle is visualized prior to injection. Ultrasound guidance can help ensure depth of needle tip location, i.e., to make sure the needle tip is within the muscle, but it is not able to tell where it is located with reference to the IZs of the entire muscle.	7
3-dimensional Innervation Zone (3DIZ) Guided Injection In the IZ-guided injection technique, IZ location obtained using the 3DIZ will be first marked over the skin surface of the muscle and the depth of the IZ will be also provided. The 3DIZ will be applied to the IZ-guided injection group 1 day prior to scheduled injection. The surface location and depth information of the IZ will be used to guide where the needle tip needs to go. Currently, patients commonly receive 1 to 2 injection sites, occasionally 3 sites for biceps muscles. To standardize the procedure, we will choose 2 sites for all patients.	8
Total	15

Baseline characteristics

Characteristic	Standard BTX Injection (Ultrasound Guided)	3-dimensional Innervation Zone (3DIZ) Guided Injection	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	2 Participants	3 Participants	5 Participants
Age, Categorical Between 18 and 65 years	5 Participants	5 Participants	10 Participants
Age, Continuous	55.43 years STANDARD_DEVIATION 11.91	52.75 years STANDARD_DEVIATION 11.9	54.00 years STANDARD_DEVIATION 11.56
Race/Ethnicity, Customized Asian	1 Participants	2 Participants	3 Participants
Race/Ethnicity, Customized Black	4 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized Hispanic	1 Participants	3 Participants	4 Participants
Race/Ethnicity, Customized Other	0 Participants	1 Participants	1 Participants
Race/Ethnicity, Customized White	1 Participants	0 Participants	1 Participants
Region of Enrollment United States	7 Participants	8 Participants	15 Participants
Sex: Female, Male Female	3 Participants	3 Participants	6 Participants
Sex: Female, Male Male	4 Participants	5 Participants	9 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 8
other Total, other adverse events	0 / 7	0 / 8
serious Total, serious adverse events	0 / 7	0 / 8

Outcome results

Primary

Spasticity as Assessed by Reflex Torque of Elbow Flexors

Each subject will receive a total of 60 degrees of computer-controlled elbow extension stretching at different speeds. The stretch ends at 10 degrees beyond the resting angle of the elbow joint during standing to offset the baseline difference among subjects. From the angle-torque relations, reflex torque is obtained after subtracting passive torque at 5˚/sec from those at 50˚/sec or 100˚/sec. Reflex torque is considered to reflect the neural component of muscle spasticity.

Time frame: baseline (1 day prior to BTX injection)