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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Kirsten Elwischger, MD, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01523210
First received: January 7, 2012
Last updated: November 12, 2012
Last verified: November 2012
  Purpose

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 Intervention
Spasticity
Other: physiotherapy

Study Type: Observational
Study Design: 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

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • change of Fractionated Anisotropie (FA) value [ Time Frame: baseline, week 3, week 16, week 19 ] [ Designated as safety issue: No ]
    FA value reflects indirect diffusion

  • change of muscle cross-sectional area after routine botulinum toxin injection [ Time Frame: baseline, week 3, week 16, week 19 ] [ Designated as safety issue: No ]
    reflected by diameter of signal changes on T2-weighted and short-tau inversion recovery (STIR) sequences

  • Change of Apparent Diffusion Coefficient (ADC) values [ Time Frame: baseline, week 3, week 16, week 19 ] [ Designated as safety issue: No ]
    ADC describes structural changes of myocytes


Enrollment: 5
Study Start Date: November 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

patients suffering from upper limb spasticity

receiving routine BoNT injection

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01523210

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

No publications provided

Responsible Party: Kirsten Elwischger, MD, MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT01523210     History of Changes
Other Study ID Numbers: DTI_BoNT_distribution
Study First Received: January 7, 2012
Last Updated: November 12, 2012
Health Authority: Austria: Ethikkommission

Keywords provided by Medical University of Vienna:
spasticity
Diffusor tensor imaging
distribution
botulinum toxin
physiotherapy

Additional relevant MeSH terms:
Muscle Spasticity
Muscular Diseases
Musculoskeletal Diseases
Muscle Hypertonia
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Botulinum Toxins
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 30, 2014