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

Spasticity Clinical Trial

Official title:

Influence of Physiotherapy on the Spastic Musculus Biceps Brachii Under Routine Botulinum Toxin Injection. - An Explorative MRI Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523210
• Other study ID #: DTI_BoNT_distribution
• Status: Completed
• Phase: N/A
• First received: January 7, 2012
• Last updated: November 12, 2012
• Start date: November 2011
• Est. completion date: November 2012

Study information

• Verified date: November 2012
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Ethikkommission
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 5
• Est. completion date: November 2012
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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

Observational Model: Case-Crossover, Time Perspective: Prospective

Related Conditions & MeSH terms

• Muscle Spasticity
• Spasticity

Intervention

Other:
• physiotherapy
thirty minutes passive flexion and extension of the elbow joint by a physiotherapist

Locations

Country	Name	City	State
Austria	Medical University of Vienna, Department of Neurology	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Kirsten Elwischger, MD

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change of Fractionated Anisotropie (FA) value	FA value reflects indirect diffusion	baseline, week 3, week 16, week 19	No
Primary	change of muscle cross-sectional area after routine botulinum toxin injection	reflected by diameter of signal changes on T2-weighted and short-tau inversion recovery (STIR) sequences	baseline, week 3, week 16, week 19	No
Primary	Change of Apparent Diffusion Coefficient (ADC) values	ADC describes structural changes of myocytes	baseline, week 3, week 16, week 19	No