Evaluation of Botulinum Toxin Injection Efficacy in the Treatment of Head Essential Tremor

NCT02555982 | Completed Phase 3

• 2 other identifiers: CHU-02452015-000162-59
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 17

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

Conditions

Essential Head Tremor

Keywords

Essential Head tremor; Botulinum toxin injections; Quality of life; Embarrassment assessment

Outcome Measures

Primary Outcomes (6)

• clinical state improvement of patients evaluated by the Clinical Global Impression of Change (CGI)

  clinical state improvement of patients evaluated by the Clinical Global Impression of Change (CGI) (improvement by at least two points) measured 6 weeks after the 2nd injection of Btx (at 18W).

  at 18 weeks

• % of responders defined with CGI

  at 6 weeks

• % of responders defined with CGI

  at 18 weeks

• The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)

  at day 0

• The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)

  at 6 weeks

• The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)

  at 12 weeks

Secondary Outcomes (27)

• The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)

  at 18 weeks

• The Fahn-Tolosa-Marin Tremor Rating Scale (TRS) (sub item head)

  at 24 weeks

• The Essential Tremor Embarrassment Assessment (ETEA)

  at day 0

• The Essential Tremor Embarrassment Assessment (ETEA)

  at 6 weeks

• The Essential Tremor Embarrassment Assessment (ETEA)

  at 12 weeks

Study Arms (2)

EXPERIMENTAL GROUP

EXPERIMENTAL

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).

Drug: BOTOX ® 200 Unités

CONTROL GROUP

OTHER

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).

Drug: Placebo

Interventions

BOTOX ® 200 Unités DRUG

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).

EXPERIMENTAL GROUP

Placebo DRUG

Control group: 60 patients will receive 2 injections of placebo, one on D0 and one at 12W (into each splenius capitis).

CONTROL GROUP

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• Allergan: collaborator

Study Sites (17)

Centre Hospitalier Pays D'Aix

Aix-en-Provence, France

Location

CHU d'Amiens

Amiens, France

Location

Hôpital Jean Minjoz

Besançon, France

Location

Hôpital Haut-Levêque

Bordeaux, France

Location

CHU de Clermont-Ferrand

Clermont-Ferrand, 63003, France

Location

Hôpital R Salendro

Lille, France

Location

Hôpital neurologique

Lyon, France

Location

Hôpital de la Timone

Marseille, France

Location

CH Narbonne

Narbonne, France

Location

Hôpital Caremeau

Nîmes, France

Location

AP-HP

Paris, France

Location

Fondation Rothschild

Paris, France

Location

Hopital Lariboisière

Paris, France

Location

Hôptal Avicenne de Bobigny

Paris, France

Location

CHU de Poitiers

Poitiers, France

Location

Hôpital de Hautepierre

Strasbourg, France

Location

CHU de Toulouse

Toulouse, France

Location

Related Publications (1)

• Marques A, Pereira B, Simonetta-Moreau M, Castelnovo G, De Verdal M, Fluchere F, Laurencin C, Degos B, Tir M, Kreisler A, Blanchet-Fourcade G, Guehl D, Colin O, Poujois A, Sangla S, Tatu L, Derost P, Gayraud D, Tranchant C, Amarantini D, Devos D, Rascol O, Corvol JC, Durif F, Rieu I; Btx-HT Study Group. Trial of Botulinum Toxin for Isolated or Essential Head Tremor. N Engl J Med. 2023 Nov 9;389(19):1753-1765. doi: 10.1056/NEJMoa2304192.

  PMID: 37937777 RESULT

Study Officials

• Franck Durif

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2015
• First Posted: September 22, 2015
• Study Start: June 27, 2016
• Primary Completion: September 17, 2021
• Study Completion: September 1, 2022
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

FR (17)