Exploring Advanced Imaging Techniques to Characterize Botulinum Toxin Diffusion in Human Muscle

Exploring Advanced Imaging Techniques to Characterize Botulinum Toxin Diffusion

Since the use of botulinum toxin in treating spasticity has already been proven effective, we are now using magnetic resonance imaging to examine the toxin diffusion within muscle (post injection) in order to determine the specific toxin dose required for an optimal treatment response.

Study Overview

• Status: Completed
• Conditions: Stroke; Muscle Spasticity
• Intervention / Treatment: Drug: Botox (botulinum toxin)

Detailed Description

Over the past decade, botulinum toxins (BT) have been extensively used to treat any number of diverse disorders, including functionally significant, focal spasticity in the arm and leg of persons with injury/disease of the central nervous system. Spasticity is an involuntary muscle stiffness that limits movement of an extremity and often leads to pain, hygiene problems, difficulty in bed or wheelchair positioning, and functional deficits in self-care and mobility.

There are three BT products on the market: MyoBloc®, Botox®, and Dysport®. FDA approval for use of Botox® in spasticity is anticipated sometime during 2010. In the Weill Cornell Division of Rehabilitation Medicine alone, nearly 50,000 units of Botox® were injected for the treatment of spasticity during the 2008-2009 academic year. (Note: The vast majority of the BT market share in the US rests with Botox®.)

There is excellent evidence supporting the effectiveness of BT in decreasing tone and modest clinical evidence supporting functional improvement. Despite the frequent use, however, there is astonishingly little evidence delineating the impact on diffusion of dosing, dilution, approach to muscle localization, or serotype of BT. To better study these relationships we will be using advanced imaging to develop a model to characterize the physical characteristics of BT diffusion in human skeletal muscle.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10065
      • New York Presbyterian Hospital/Weill Cornell Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of UMN disease
• clinically significant spasticity in the gastrocnemius muscle to warrant Botox® injection (made at the discretion of Dr. O'Dell)
• naïve to all botulinum toxins in the lower extremity

Exclusion Criteria:

• MR incompatibility with implanted ferromagnetic devices.[Specifically, they may not participate in this study if they have a pacemaker, an implanted defibrillator or certain other implanted electronic or metallic devices. They will be screened by the MRI staff for past surgical procedures to determine the possibility of having an implanted medical or metallic device, shrapnel, or other metal, such as metal in the eye.]
• Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

No Intervention: botox diffusion; Each subject was given 3 injections in lateral gastrocnemius muscle:2 botox, 1 saline, each injection was 2.5mL. MRI of the lower leg was taken prior to injections and 2 months post for a comparison of diffusion properties.

Drug: Botox (botulinum toxin); A series of three injections will be made simultaneously to the gastroc-soleus muscles of the affected lower limb; this will be the only drug intervention/injection session throughout the study, and occurs at baseline. The top injection site, closest to the knee, consists of 25 units of Botox and 0.25 cc saline. The bottom injection site, closest to the ankle, also consists of 25 units of Botox and 0.25 cc saline. The middle injection site will be considered the placebo injection, as it will not contain any Botox (0 units Botox) and 0.25 cc saline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MRI	Subjects will undergo non-contrast MRI's of the target leg prior to Botox injections (0 months), then again at both 2 months and 3 months following the Botox injections.	Baseline (0 months), 2 months and 3 months

Collaborators and Investigators

• Sponsor: New York Presbyterian Hospital
• Investigators: Principal Investigator: Michael W O'Dell, MD, Weill Medical College of Cornell University

Publications and helpful links

Helpful Links

• NYPH/WCMC Rehabilitation Medicine Research/Trials Site

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: August 4, 2011
• First Submitted That Met QC Criteria: August 4, 2011
• First Posted (Estimate): August 8, 2011

Study Record Updates

• Last Update Posted (Estimate): October 1, 2013
• Last Update Submitted That Met QC Criteria: September 27, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: MRI; stroke; Magnetic Resonance Imaging; spasticity; botulinum toxin; muscle stiffness; Botox; neurological; diffusion; Weill Cornell; New York Presbyterian Hospital; O'Dell
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Muscle Spasticity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Botulinum Toxins
• Other Study ID Numbers: 1002010863