The Movement of Botulinum Toxin Through the Lateral Gastrocnemius Muscle in Humans: An Expanded Examination

NCT03367429 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: 1708018456
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

Despite the wide-spread use of botulinum toxin (BT) to treat spasticity (increased muscle tone) in central neurological disease, evidence-based guidance on dosing, dilution, and injection technique is limited. The wide-spread use of BT in spasticity management, expense of these agents, and detrimental impact from movement into non-injected muscles mandates a better understanding of BT movement within muscles. A proof-of-concept paper written by investigators at Weill Cornell Medicine introduced a non-invasive MRI approach with "voxel thresholds" that was able to detect intramuscular effects of BT at 2 and 3 months post-injection of BT. The purpose of the current set of studies is to refine this MRI technique to better visualize the movement of botulinum toxin through muscle. In addition, the investigators plan to explore, using the imaging technique, how spastic muscle and differing dilutions affect BT movement in an effort to support the development of better research techniques to study toxin movement in human muscle.

Conditions

Stroke; Muscle Spasticity

Keywords

stroke; spasticity

Outcome Measures

Primary Outcomes (1)

• Botulinum Toxin Muscle Effect (BTME) Volume of Abnormal Voxels Per MRI Slice in Muscles After Research Injections

  BTME volume is calculated by counting the number of abnormal voxels (each voxel volume is .0015 cc) on MRI2, which have a relaxation time greater than or equal to 3 standard deviations above the baseline mean for a subject and their muscle found on their baseline MRI.

  At MRI 2, 2 Months after Research Injection

Secondary Outcomes (1)

• Change in Botulinum Toxin Muscle Effect (BTME) Volume of Abnormal Voxels Per MRI Slice in Muscles After Clinical Injections

  At MRI 3, 2 Months after Clinical Injections

Study Arms (2)

Exp 2 & 3 - Arm 1

EXPERIMENTAL

If within-subject design is adopted, subjects will receive one experimental BT injection of 25 units onobotulinumtoxinA (Botox®) diluted in 0.50 cc of saline to their spastic LGM and one standard BT injection of of 25 units onobotulinumtoxinA (Botox®) diluted in 0.25 cc of saline to their spastic MGM. If between-subjects design is adopted, subjects will receive one experimental BT injection of 25 units onobotulinumtoxinA (Botox®) diluted in 0.50 cc of saline to their spastic LGM.

Drug: Botox

Exp 2 & 3 - Arm 2

EXPERIMENTAL

If within-subject study design is adopted, subjects will receive one standard BT injection of 25 units onobotulinumtoxinA (Botox®) diluted in 0.25 cc of saline to their spastic LGM and one experimental BT injection of 25 units onobotulinumtoxinA (Botox®) diluted in 0.50 cc of saline to their spastic MGM. If between-subjects design is adopted, subjects will receive one standard BT injection of 25 units onobotulinumtoxinA (Botox®) diluted in 0.25 cc of saline to their spastic LGM.

Drug: Botox

Interventions

Botox DRUG

THE PROTOCOL DESCRIPTION ATTEMPTED TO OUTLINE A CONTINGINECY PLAN- MOVING TO ONE OF TWO METHODOLOGOIES DPENDING ON PRELIMINARY FINDINGS. UNFORTUNATLEY, OVER 2 YEARS RECRUITMENT WAS GROSSLY INADEQUATE PREVENTING ANY TYPE OF EVEN CURSURY PRELIMINARY DATA ANALYSIS AND FORCING THE EARLY TERMINATION OF THIS STUDY. MICHAEL W. O'DELL, MD

Exp 2 & 3 - Arm 1; Exp 2 & 3 - Arm 2

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female aged 30-75
• Diagnosis of any stroke (ischemic or hemorrhagic, first occurrence or recurrent)
• Clinically significant lower extremity spasticity as assessed by PI that would benefit from BT treatment
• Ambulatory with or without device and without assistance at household or greater level
• Indication to inject gastrocnemius muscle (any combination of spastic lower extremity muscle injections are acceptable)
• Goal of treatment may include improvement of gait, ankle range of motion, ankle foot orthosis fit, heel strike, ankle position in stance phase, decreased clonus, or relief from painful muscle spasms
• Naïve to BT of any serotype in any lower extremity muscle
• Naïve to phenol or alcohol treatment in any lower extremity muscle

You may not qualify if:

• History of concomitant neurological disease (central or peripheral) other than stroke
• Contraindication to intramuscular injection of BT
• Medically unstable as determined by PI
• Have an intrathecal baclofen pump
• Contraindication for MRI (Subjects with MRI-compatible hip replacements may participate, but not those with total knee replacements due to artifact)

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Allergan: collaborator

Study Sites (1)

NewYork Presbyterian Hospital - Weill Cornell Medicine

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Stroke; Muscle Spasticity

Interventions

Botulinum Toxins, Type A

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Michael O'Dell, M.D.
• Organization: Weill Cornell Medicine

mio2005@med.cornell.edu

19175495179

Study Officials

• Michael O'Dell, M.D.

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: If the within-subject design is used, N=15 and subjects will be randomized 1:1 to receive the standard injection to either the LGM or MGM. The experimental injection will be delivered to the muscle not receiving the standard injection. If the between-subject design must be used, N=25 and subjects will be randomized 2:3 to receive either the experimental or standard injection to the spastic LGM. Please note the following: Standard Injection: 25 units of onobotulinumtoxinA (Botox®) diluted in 0.25cc of saline. Experimental Injection: 25 units of onobutilinumtoxinA (Botox®) diluted in 0.50cc of saline.

Study Record Dates

• First Submitted: November 16, 2017
• First Posted: December 8, 2017
• Study Start: June 15, 2018
• Primary Completion: September 18, 2019
• Study Completion: September 18, 2019
• Last Updated: December 29, 2021
• Results First Posted: December 29, 2021

Record last verified: 2021-11

Locations

US (1)