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

NCT ID: NCT02555982

Last Updated: 2022-12-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-27
• Study Completion Date: 2022-09-01

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.

Conditions

Essential Head Tremor

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

EXPERIMENTAL GROUP

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).

Group Type: EXPERIMENTAL

BOTOX ® 200 Unités

Intervention Type: 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).

CONTROL GROUP

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).

Group Type: OTHER

Placebo

Intervention Type: DRUG

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

Interventions

BOTOX ® 200 Unités

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).

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Allergan

INDUSTRY

Sponsor Role: collaborator

University Hospital, Clermont-Ferrand

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Franck Durif

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Clermont-Ferrand

Locations

Centre Hospitalier Pays D'Aix

Aix-en-Provence, , France

CHU d'Amiens

Amiens, , France

Hôpital Jean Minjoz

Besançon, , France

Hôpital Haut-Levêque

Bordeaux, , France

CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Hôpital R Salendro

Lille, , France

Hôpital neurologique

Lyon, , France

Hôpital de la Timone

Marseille, , France

CH Narbonne

Narbonne, , France

Hôpital Caremeau

Nîmes, , France

AP-HP

Paris, , France

Fondation Rothschild

Paris, , France

Hopital Lariboisière

Paris, , France

Hôptal Avicenne de Bobigny

Paris, , France

CHU de Poitiers

Poitiers, , France

Hôpital de Hautepierre

Strasbourg, , France

CHU de Toulouse

Toulouse, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 37937777 (View on PubMed)

Other Identifiers

2015-000162-59

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHU-0245

Identifier Type: -

Identifier Source: org_study_id