ActivePhase 3ACTRN12617000379314

A clinical trial to study the safety and efficacy of Botox for arm tremor in people with multiple sclerosis (MS)

A randomized controlled trial of the efficacy of Botulinum Toxin type A in the treatment of MS tremor: a clinical, imaging and electrophysiological approach


Sponsor

University of Melbourne

Enrollment

100 participants

Start Date

Aug 8, 2016

Study Type

Interventional

Conditions

Summary

The treatment and pathophysiology of tremor in Multiple Sclerosis (MS) remains a significant challenge and unmet need, requiring further clinical research. We recently performed a phase II, randomized, controlled, crossover study demonstrating the efficacy of Botulinum toxin type A (BoNT-A) for treatment of MS tremor. This peer-reviewed NHMRC funded project proposes a detailed study of phenomenological, electrophysiological characteristics of MS tremor patients before and after BoNT-A or placebo treatment. The results of this study will help generate class I evidence that is required to translate treatment of MS tremor with BoNT-A into clinical practice. We aim to define predictors of the response to treatment and to better understand the underlying pathophysiology of MS tremor.


Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria6

  • a definite diagnosis of RRMS (38) or SPMS (39)
  • aged between 18 and 65 years
  • no other neurological disease to explain presence of tremor
  • no MS relapse or treatment with corticosteroids in the 3 months prior to
  • enrollment
  • normal or near-normal upper limb strength (Medical Research Council (MRC) score > 4+/5).

Exclusion Criteria6

  • Treatment of tremor with Botulinum toxin type A of any brand within the 6 months prior to enrollment
  • A known contraindication to Botox injection
  • Pregnancy, breastfeeding or unwillingness to use adequate contraception.
  • Inability to cease other tremor treatments (wash-out period of 4 weeks for any tremor reducing agents)
  • A MS relapse during the study that affects upper limb function will be a withdrawal criterion.
  • Any contra-indication to MRI will exclude the patient from MRI protocol.

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Interventions

This is a 24 week randomized controlled study of onabotulinumtoxina compared to placebo. Randomization is 1:1. An open-label extension starts at the 24 week visit with further follow-up to 48 weeks.

This is a 24 week randomized controlled study of onabotulinumtoxina compared to placebo. Randomization is 1:1. An open-label extension starts at the 24 week visit with further follow-up to 48 weeks. Details of the therapeutic intervention is as follows: Botulinum toxin A (onabotulinumtoxina) affects neuromuscular transmission by blocking calcium-mediated exocytosis of acetylcholine. Transmission of acetylcholine is restored over 2 to 4 months in human motor endplates, although the clinical effects may persist for 6 months. The medication is administered as an intramuscular injection. A maximum dose of 150 IU will be administered at baseline and/or at 6 months with the actual dosed determined by the treating neurologist. Dosages are individualised to target muscles according to the type of tremor observed. Data from our previous study (Van der Walt et al. Neurology, 2010) showed that the average dose per person is 83 IU per treatment with an average of 5 muscles injected. There is no minimum dose. Placebo The placebo intervention will be normal saline.


Locations(1)

Royal Melbourne Hospital - City campus - Parkville

VIC, Australia

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