Evaluation of Botulinum Toxin Injection Efficacy in the Treatment of Head Essential Tremor
Condition: Essential Head Tremor
MeSH terms: Tremor; Essential Tremor
Study type: Interventional
Phase: Phase 3

Summary: 
      Essential head tremor (HT) does not usually respond to drug treatment such as propranolol or
      primidone or to surgical treatment such as deep brain stimulation of the thalamic ventralis
      intermedius nucleus. Botulinum toxin (Btx) is widely used and efficient in the treatment of
      blepharospasm and cervical dystonia. Btx prevents the release of acetylcholine in synapses,
      leading to a reduction of pathological muscle movement. Very little information is available
      on its efficacy on HT. Two published reports suggested that local Btx A injections could be
      an effective and safe approach for treating HT. Given the scarcity of published data (small
      samples, open studies, different doses of Btx used, heterogeneous populations, several
      muscles injected, etc.), the aim of this study is to demonstrate the efficacy of Btx
      injections in essential HT by a multi-center, randomized, double-blind, parallel-group,
      placebo-controlled study.

      Principal objective: To evaluate the efficacy of botulinum toxin injections in the treatment
      of head tremor.

      Secondary objectives:

        -  - To evaluate the tolerance of botulinum toxin injections in the treatment of head
           tremor.

        -  - To evaluate the impact of botulinum toxin injections on the patients' quality of life
           and embarrassment.

        -  To evaluate the changes of tremor characteristics induced by a Btx treatment using a 3D
           accelerometer wireless portable system (Xsens MTw wireless motion tracker system)
           (tremor frequency, tremor displacement, mean peak amplitude, distance traveled) and a
           new video system device to analyze head tremor characteristics
    

Detailed description: 
      Type of study: multi-center, randomized, double-blind, parallel-group, placebo-controlled
      therapeutic clinical trial.

      Number of centers: 19 centers : Clermont-Ferrand, Paris (Fondation Rothschild, APHP, Hôpital
      Lariboisière, Hôpital Avicenne de Bobigny), Toulouse, Lyon, Amiens, Bordeaux, Narbonne,
      Lille, Strasbourg, Nîmes, Marseille, Besançon, Aix, Montpellier, Pau,Poitiers

      Medical product Botulinum toxin type A, 200U (BOTOX ® 200 Unités, Allergan)

      Patients

      Patients eligible for inclusion will be randomized to one of the two groups:

        -  Experimental group: 60 patients will receive 2 injections of Btx A (BOTOX - Allergan),
           one on D0 and one at 12W (into each splenius capitis).

        -  Control group: 60 patients will receive 2 injections of placebo, one on D0 and one at
           12W (into each splenius capitis).

      Study Performance Patients will be injected twice, with an interval of 12 weeks (D0 and 12W).
      On D0, patients will receive 75U of Btx A (BOTOX ® - Allergan) in each splenius capitis; at
      12W, patients will receive the same dose as on D0 (if the first injection is effective
      according to the CGI- improvement by at least two points), or a higher dose (100U) (if the
      first injection is ineffective according to the CGI- non improvement or improvement by less
      than two points).

      Patients will be assessed at baseline D0, 6 weeks (6W), 12 weeks (12W), 18 weeks (18W) and 24
      weeks (24W) after D0 as follows:

      Visit 1 (baseline):

        -  Signature of an informed consent form.

        -  Demographic and clinical characteristics (sex, age, disease duration, treatments).

        -  Clinical evaluation:

        -  Neurological evaluation: Fahn-Tolosa-Marin Tremor Rating Scale (TRS), Tsui Scale.

        -  The Quality of life in Essential Tremor (QUEST), the Essential Tremor Embarrassment
           Assessment (ETEA).

        -  Accelerometer recording and videotape recording.

      Visits at 6W, 12W, 18W and 24W

        -  Clinical evaluation:

        -  TRS.

        -  CGI.

        -  QUEST / ETEA.

        -  Accelerometer recording and videotape recording.
    

Intervention name(s): BOTOX ® 200 Unités; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Patients eligible for inclusion will be randomized to one of the two groups:
Experimental group: 60 patients will receive 2 injections of Btx A (BOTOX - Allergan), one on D0 and one at 12W (into each splenius capitis).
Control group: 60 patients will receive 2 injections of placebo, one on D0 and one at 12W (into each splenius capitis).; Control group: 60 patients will receive 2 injections of placebo, one on D0 and one at 12W (into each splenius capitis).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Essential Head tremor; Botulinum toxin injections; Quality of life; Embarrassment assessment