Clinical trial NCT01162291: Comparison of Intramuscular Distribution of Different Injection Volumes Via Diffusion Tensor Imaging (DTI)
Official title: Comparison of Intramuscular Distribution of Different Injection Volumes Via Diffusion Tensor Imaging (DTI)-A Pilot Trial
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy
Keywords: intramuscular
distribution
NaCl
botulinum toxin
muscle
volume
movement
biceps brachii
primary distribution of intramuscular NaCl representative for primary distribution of intramuscular botulinum toxin
shift from extracellular to intracellular viewed by DTI technology
effect of volume
effect of muscle movement
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2010-07-14
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: healthy volunteer

Brief summary: The purpose of this experimental pilot study is to assess a positive effect of higher injection volumes of fluid (physiological sodium) in the elbow-flection-muscle (M. biceps brachii) and elbow flexion and extension movements on fluid distribution in the muscle tissue.

Detailed description: Background:

Intramuscular application of Botulinum toxin is used as a successful therapy of many conditions (e.g. spasticity, movement disorders, hypersecretory disorders, ophthalmic disorders, painful conditions, pelvic floor and gastrointestinal disorders, cosmetic applications) Clinical practice shows that even with the use of special guidance techniques (electromyography (EMG), ultrasound, electrical stimulation) to increase accuracy of targeting, botulinum toxin may spread to adjacent sites by diffusion. Different therapy goals request variable diffusion of the toxin, depending on the number of muscles involved and loss of function in the affected area, respectively. There is some evidence that larger injection volume lead to greater distribution and a larger affected area. Thus, animal model showed increased efficacy and decreased systemic side effects of botulinum toxin A in the injected muscle after active or passive manipulation of muscle.

Magnetic resonance imaging (MRI) has the potential to noninvasively probe the amount and motion of intracellular and extracellular water using different sequences. T2-weighted and diffusion tensor sequences are especially useful in the quantification and characterization of the chemical behaviour of water in different (animal) tissue types. To our knowledge there has been no systematically performed in vivo MR study using these imaging techniques in the visualization of intramuscular dilution of fluid in human subjects. However, the in vivo effect on tissue distribution of different injection volumes and active muscle movement in humans via DTI has never been observed.

Hypothesis:

Intramuscular distribution of common saline solutions can be non-invasively quantified by DTI in human subjects. DTI can be used to elucidate if:

* Intramuscular distribution is favoured by larger injection volumes and
* Intramuscular distribution is facilitated by active muscle activity.

Rationale:

The effect of large injection volumes and active muscle activity after injection on intramuscular toxin distribution and uptake remains unclear. Physiological sodium is the carrier material of all preparations of Botulinum toxin, suggesting that physiological sodium or natriumchlorid (NaCl) distribution is representative for toxin primary distribution. Dynamic T2-weighted sequences may monitor the inflow and regional distribution of the infused saline solution.

DTI can non-invasively quantify the amount and directionality of motion of protons in human skeletal muscle and may therefore indirectly allow assumptions on the extra- and intracellular distribution of the infused solution/substance.

Methods:

In this exploratory, investigator blinded pilot study, 10 healthy subjects will be investigated by DTI of the musculi biceps brachii after randomised intramuscular injection of two different injection volumes of NaCl and randomisation to active flexion and extension in the elbow joints versus no active flexion and extension. During each injection dynamic T2 weighted magnetic resonance tomographic sequences will be performed. Subsequently diffusion tensor sequences will be carried out at defined time points.

Eligibility criteria: Inclusion Criteria:

* healthy volunteer
* willing to participate in this clinical pilot trial
* age 18-80 years old

Exclusion Criteria:

* bleeding disorder or acute bleeding event
* coumarines, warfarin therapy
* any type of medical implant (pacemaker, prosthesis, etc.) not meeting the general safety recommendations for 3 tesla MR imaging

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University of Vienna, Department of Neurology
Study officials:
affiliation: Medical University of Vienna
name: Thomas Sycha, Prof., MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hsu TS, Dover JS, Arndt KA. Effect of volume and concentration on the diffusion of botulinum exotoxin A. Arch Dermatol. 2004 Nov;140(11):1351-4. doi: 10.1001/archderm.140.11.1351.
citation: Minamoto VB, Hulst JB, Lim M, Peace WJ, Bremner SN, Ward SR, Lieber RL. Increased efficacy and decreased systemic-effects of botulinum toxin A injection after active or passive muscle manipulation. Dev Med Child Neurol. 2007 Dec;49(12):907-14. doi: 10.1111/j.1469-8749.2007.00907.x.
citation: Kranz G, Haubenberger D, Voller B, Posch M, Schnider P, Auff E, Sycha T. Respective potencies of Botox and Dysport in a human skin model: a randomized, double-blind study. Mov Disord. 2009 Jan 30;24(2):231-6. doi: 10.1002/mds.22336.
citation: Fan RH, Does MD. Compartmental relaxation and diffusion tensor imaging measurements in vivo in lambda-carrageenan-induced edema in rat skeletal muscle. NMR Biomed. 2008 Jul;21(6):566-73. doi: 10.1002/nbm.1226.
citation: Zaraiskaya T, Kumbhare D, Noseworthy MD. Diffusion tensor imaging in evaluation of human skeletal muscle injury. J Magn Reson Imaging. 2006 Aug;24(2):402-8. doi: 10.1002/jmri.20651.