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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01523210
Recruitment Status : Completed
First Posted : February 1, 2012
Last Update Posted : November 14, 2012
Information provided by (Responsible Party):
Kirsten Elwischger, MD, Medical University of Vienna

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.

Condition or disease Intervention/treatment
Spasticity Other: physiotherapy

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 Type : Observational
Actual Enrollment : 5 participants
Observational Model: Case-Crossover
Time Perspective: Prospective
Official Title: Influence of Physiotherapy on the Spastic Musculus Biceps Brachii Under Routine Botulinum Toxin Injection. - An Explorative MRI Study
Study Start Date : November 2011
Actual Primary Completion Date : November 2012
Actual Study Completion Date : November 2012

Group/Cohort Intervention/treatment
upper limb spasticity
patients suffering from upper limb spasticity and are treated with botulinum toxin
Other: physiotherapy
thirty minutes passive flexion and extension of the elbow joint by a physiotherapist
Other Name: physical therapy

Primary Outcome Measures :
  1. change of Fractionated Anisotropie (FA) value [ Time Frame: baseline, week 3, week 16, week 19 ]
    FA value reflects indirect diffusion

  2. change of muscle cross-sectional area after routine botulinum toxin injection [ Time Frame: baseline, week 3, week 16, week 19 ]
    reflected by diameter of signal changes on T2-weighted and short-tau inversion recovery (STIR) sequences

  3. Change of Apparent Diffusion Coefficient (ADC) values [ Time Frame: baseline, week 3, week 16, week 19 ]
    ADC describes structural changes of myocytes

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

patients suffering from upper limb spasticity

receiving routine BoNT injection


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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01523210

Medical University of Vienna, Department of Neurology
Vienna, Austria, 1090
Sponsors and Collaborators
Kirsten Elwischger, MD
Principal Investigator: Thomas Sycha, Prof., MD Medical University of Vienna, Department of Neurology

Responsible Party: Kirsten Elwischger, MD, MD, Medical University of Vienna Identifier: NCT01523210     History of Changes
Other Study ID Numbers: DTI_BoNT_distribution
First Posted: February 1, 2012    Key Record Dates
Last Update Posted: November 14, 2012
Last Verified: November 2012

Keywords provided by Kirsten Elwischger, MD, Medical University of Vienna:
Diffusor tensor imaging
botulinum toxin

Additional relevant MeSH terms:
Muscle Spasticity
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Botulinum Toxins
Acetylcholine Release Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs