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

NCT03302741 | Completed Phase 4 Results FDA Drug FDA Device

• 1 other identifier: HSC-MS-17-0174
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

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.

Conditions

Spasticity

Keywords

stroke

Outcome Measures

Primary Outcomes (3)

• 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.

  baseline (1 day prior to BTX injection)

• 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.

  3 weeks after BTX injection

• 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.

  3 months after BTX injection

Secondary Outcomes (3)

• Spasticity as Assessed by the Modified Ashworth Scale (MAS)

  baseline (1 day prior to BTX injection)

• Spasticity as Assessed by the Modified Ashworth Scale (MAS)

  3 weeks after BTX injection

• Spasticity as Assessed by the Modified Ashworth Scale (MAS)

  3 months after BTX injection

Study Arms (2)

Standard BTX injection (ultrasound guided)

ACTIVE COMPARATOR

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.

Drug: Botulinum neurotoxin (BTX); Other: Physical Therapy; Device: Standard BTX injection (ultrasound guided)

3-dimensional innervation zone (3DIZ) guided injection

EXPERIMENTAL

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.

Drug: Botulinum neurotoxin (BTX); Other: Physical Therapy; Device: 3-dimensional innervation zone (3DIZ) guided injection

Interventions

Botulinum neurotoxin (BTX) DRUG

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

Also known as: Botox

3-dimensional innervation zone (3DIZ) guided injection; Standard BTX injection (ultrasound guided)

Physical Therapy OTHER

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

3-dimensional innervation zone (3DIZ) guided injection; Standard BTX injection (ultrasound guided)

Standard BTX injection (ultrasound guided) DEVICE

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.

Standard BTX injection (ultrasound guided)

3-dimensional innervation zone (3DIZ) guided injection DEVICE

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.

3-dimensional innervation zone (3DIZ) guided injection

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• University of Houston: collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 70030, United States

Location

MeSH Terms

Conditions

Muscle Spasticity; Stroke

Interventions

Botulinum Toxins; Botulinum Toxins, Type A; Physical Therapy Modalities

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Therapeutics; Rehabilitation

Results Point of Contact

• Title: Sheng Li, MD, PhD
• Organization: The University of Texas Health Science Center at Houston

sheng.li@uth.tmc.edu

713-797-7125

Study Officials

• Sheng Li, MD, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 1, 2017
• First Posted: October 5, 2017
• Study Start: November 21, 2017
• Primary Completion: November 18, 2019
• Study Completion: November 18, 2019
• Last Updated: November 5, 2020
• Results First Posted: November 5, 2020

Record last verified: 2020-10

Locations

US (1)