DTI Study of the Influence of Physiotherapy on Distribution of BoNT in Spastic Muscle

Completed

• Conditions: Spasticity
• Interventions: Other: physiotherapy

• Registration Number: NCT01523210
• Lead Sponsor: Kirsten Elwischger, MD

Brief Summary

Intramuscular application of botulinum toxin (BoNT) is used as a successful therapy of muscle spasticity. Clinical practice shows, that even with the use of special guidance techniques to increase accuracy of targeting, BoNT may spread to adjacent sites by diffusion. This causes fluctuating treatment response, unintended side effects, and decrease of effect due to production of antibodies. Hence, clinicians require increase of efficacy and safety by dose reduction, improvement of injection technique, and additional treatment strategies. Referring to this, animal model showed increased efficacy and decreased systemic side effects of BoNT in the injected muscle after active or passive manipulation of muscle. The mechanism of this effect remain unclear.

T2 and (Diffusion Tensor Imaging) DTI technique can evaluate the in-vivo distribution of fluids in human skeletal muscle. In addition, it allows to differentiate denervated muscle tissue, caused by BoNT injections, from surrounding unaffected muscle tissue.

Up to the investigators knowledge, neither a human, in vivo measurement of the influence of passive muscle activity on the area of denervation, nor the primary, in-vivo distribution of BoNT within spastic human muscle tissue, been evaluated.

The aim of this explorative study is:

* to monitor the inflow and regional distribution of the injection bolus by dynamic T2-weighted-, DTI-sequences;

* to assess the effect of passive muscle exercise on the area of denervated, caused by BoNT, measured by DTI-, T2-weighted and flair sequences.

The investigators hypothesize, that

* intramuscular denervation area, measured by DTI-, T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) sequences, 3 weeks after routine BoNT injection, is facilitated by passive muscle exercise;

* primary distribution of the injected BoNT bolus can be non-invasively monitored by dynamic T2-, DTI- and T2 weighted sequences.

Therefore, in this investigator blinded, cross-over study, 6 patients suffering from upper limb spasticity, including musculus biceps brachii, will be investigated. (Magnetic Resonance Tomography) MRI of the musculus biceps brachii will be performed at two consecutive, routine BoNT-injection days (baseline and week 16). Patients receive dosage as clinically indicated, due to routine treatment. Patients will be randomised to receive thirty minutes of physiotherapy of the affected arm, including exercise of the elbow flexors, at one of the injection days (baseline, or week 16, respectively). In addition, MRI will be repeated 3 weeks after injection.

Detailed Description

* At baseline and week 16, dynamic T2-, T2-,and DTI weighted sequences will be performed to monitor the injection of the BoNT-bolus. Immediate after MRI-scan, physiotherapy will be performed. Patients, who were randomised to the non-treatment group at baseline, will receive physiotherapy immediately after MRI at week 16.

* At week 3 and week 19, three weeks after BoNT injection, respectively, MRI will be repeated. T2-and DTI- weighted and FLAIR- sequences will be performed.

Study Timeline

• Study Start: 2011-11
• Study First Submitted: 2012-01-07
• Study First Submitted QC: 2012-01-28
• Study First Posted: 2012-02-01
• Status Verified: 2012-11
• Primary Completion: 2012-11
• Study Completion: 2012-11
• Last Update Submitted: 2012-11-12
• Last Update Posted: 2012-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

• willing to participate in this clinical pilot trial
• age 18-80 years
• ≥4 months under routine botulinum toxin treatment
• last botulinum toxin treatment ≥3 months before screening
• spasticity of m. biceps brachii elbow flexion: Modified Ashworth Scale (MAS) ≥3

Exclusion Criteria

• bleeding disorders or acute bleeding event.
• coumarine, warfarine therapy.
• non-MRI compatible medical (prothetics, pacemaker, etc) or non medical implantation (tattoos, intraorbital metal splinters, etc.) or other contraindications for MRI, not meeting the general safety recommendations for 3Tesla MRI.
• claustrophobia.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
upper limb spasticity	physiotherapy	patients suffering from upper limb spasticity and are treated with botulinum toxin

Primary Outcome Measures

Name	Time	Method
change of Fractionated Anisotropie (FA) value	baseline, week 3, week 16, week 19	FA value reflects indirect diffusion
change of muscle cross-sectional area after routine botulinum toxin injection	baseline, week 3, week 16, week 19	reflected by diameter of signal changes on T2-weighted and short-tau inversion recovery (STIR) sequences
Change of Apparent Diffusion Coefficient (ADC) values	baseline, week 3, week 16, week 19	ADC describes structural changes of myocytes

Trial Locations

Locations (1)

Medical University of Vienna, Department of Neurology; 🇦🇹 Vienna, Austria