Clinical trial NCT01523210: DTI Study of the Influence of Physiotherapy on Distribution of BoNT in Spastic Muscle
Official title: Influence of Physiotherapy on the Spastic Musculus Biceps Brachii Under Routine Botulinum Toxin Injection. - An Explorative MRI Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Spasticity
Keywords: spasticity
Diffusor tensor imaging
distribution
botulinum toxin
physiotherapy
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2012-02-01
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CROSSOVER
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: patients suffering from upper limb spasticity

receiving routine BoNT injection

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.

Eligibility criteria: 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.

Primary outcomes:
measure: change of Fractionated Anisotropie (FA) value
timeFrame: baseline, week 3, week 16, week 19
measure: change of muscle cross-sectional area after routine botulinum toxin injection
timeFrame: baseline, week 3, week 16, week 19
measure: Change of Apparent Diffusion Coefficient (ADC) values
timeFrame: baseline, week 3, week 16, week 19
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Neurology
Study officials:
affiliation: Medical University of Vienna, Department of Neurology
name: Thomas Sycha, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References: