Clinical trial NCT02555982: Evaluation of Botulinum Toxin Injection Efficacy in the Treatment of Head Essential Tremor
Official title: Evaluation of Botulinum Toxin Injection Efficacy in the Treatment of Head Essential Tremor by a Multi-center, Randomized, Double-Blind, Parallel-group, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Essential Head Tremor
Keywords: Essential Head tremor
Botulinum toxin injections
Quality of life
Embarrassment assessment
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2015-09-22
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Patients suffering from a head tremor without (isolated) or with associated
* tremor in any other body parts.
* The HT must be troublesome for the patients (TRS 2 for the head tremor
* severity item).
* Patients never treated with botulinum toxin or not treated with botulinum toxin for this indication for at least 4 months.
* Men or women aged from 18 to 80 years old.
* Social security coverage.
* Ability to provide informed consent.

Exclusion Criteria:

* Patients with tremor from cerebellar syndrome (multiple sclerosis, etc.).
* Patients with a predominant dystonic jerky or myoclonic head tremor using
* the Tsui scale (\>1).
* Oral treatments for HT are allowed but must be stable during the study.
* Any contra-indication to Botulinum toxin.
* Women without efficient contraception.
* Patients under supervision or (legal) guardianship.

Primary outcomes:
measure: clinical state improvement of patients evaluated by the Clinical Global Impression of Change (CGI)
timeFrame: at 18 weeks
measure: % of responders defined with CGI
timeFrame: at 6 weeks
measure: % of responders defined with CGI
timeFrame: at 18 weeks
measure: The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)
timeFrame: at day 0
measure: The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)
timeFrame: at 6 weeks
measure: The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)
timeFrame: at 12 weeks
Secondary outcomes:
measure: The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)
timeFrame: at 18 weeks
measure: The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)
timeFrame: at 24 weeks
measure: The Essential Tremor Embarrassment Assessment (ETEA)
timeFrame: at day 0
measure: The Essential Tremor Embarrassment Assessment (ETEA)
timeFrame: at 6 weeks
measure: The Essential Tremor Embarrassment Assessment (ETEA)
timeFrame: at 12 weeks
measure: The Essential Tremor Embarrassment Assessment (ETEA)
timeFrame: at 18 weeks
measure: The Essential Tremor Embarrassment Assessment (ETEA)
timeFrame: at 24 weeks
measure: The Quality of life in Essential Tremor (QUEST)
timeFrame: at day 0
measure: The Quality of life in Essential Tremor (QUEST)
timeFrame: at 6 weeks
measure: The Quality of life in Essential Tremor (QUEST)
timeFrame: at 12 weeks
measure: The Quality of life in Essential Tremor (QUEST)
timeFrame: at 18 weeks
measure: The Quality of life in Essential Tremor (QUEST)
timeFrame: at 24 weeks
measure: tremor frequency measured by accelerometer
timeFrame: at day 0
measure: tremor frequency measured by accelerometer
timeFrame: at 6 weeks
measure: tremor frequency measured by accelerometer
timeFrame: at 12 weeks
measure: tremor frequency measured by accelerometer
timeFrame: at 18 weeks
measure: tremor frequency measured by accelerometer
timeFrame: at 24 weeks
measure: mean peak amplitude measured by accelerometer
timeFrame: at day 0
measure: mean peak amplitude measured by accelerometer
timeFrame: at 6 weeks
measure: mean peak amplitude measured by accelerometer
timeFrame: at 12 weeks
measure: mean peak amplitude measured by accelerometer
timeFrame: at 18 weeks
measure: mean peak amplitude measured by accelerometer
timeFrame: at 24 weeks
measure: distance traveled measured by accelerometer
timeFrame: at day 0
measure: distance traveled measured by accelerometer
timeFrame: at 6 weeks
measure: distance traveled measured by accelerometer
timeFrame: at 12 weeks
measure: distance traveled measured by accelerometer
timeFrame: at 18 weeks
measure: distance traveled measured by accelerometer
timeFrame: at 24 weeks
Other outcomes:
Locations:
city: Aix-en-Provence
country: France
facility: Centre Hospitalier Pays D'Aix
city: Amiens
country: France
facility: CHU d'Amiens
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: Bordeaux
country: France
facility: Hôpital Haut-Levêque
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand
city: Lille
country: France
facility: Hôpital R Salendro
city: Lyon
country: France
facility: Hôpital neurologique
city: Marseille
country: France
facility: Hôpital de la Timone
city: Narbonne
country: France
facility: CH Narbonne
city: Nîmes
country: France
facility: Hôpital Caremeau
city: Paris
country: France
facility: AP-HP
city: Paris
country: France
facility: Fondation Rothschild
city: Paris
country: France
facility: Hopital Lariboisière
city: Paris
country: France
facility: Hôptal Avicenne de Bobigny
city: Poitiers
country: France
facility: CHU de Poitiers
city: Strasbourg
country: France
facility: Hôpital de Hautepierre
city: Toulouse
country: France
facility: CHU de Toulouse
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Franck Durif
role: PRINCIPAL_INVESTIGATOR
References: