Study to Assess the Efficacy and Safety of Dysport® in Cervical Dystonia

Multicentre Open Study on the Efficacy and Safety of Botulinum Toxin A (500 Units Dysport®) in the Treatment of Heterogeneous Forms of Cervical Dystonia

The aim is to demonstrate equivalent efficacy and safety in the treatment of the two most frequent forms of cervical dystonia (predominantly rotational torticollis and predominantly laterocollis) with the standard initial dose of 500 units Dysport®. The patients will be assigned to one of the two basic types of cervical dystonia, either predominantly rotational torticollis or predominantly laterocollis on the basis of clinical examination. This will determine which therapy is to be administered, using the clearly defined, structured injection protocols.

Study Overview

• Status: Completed
• Conditions: Cervical Dystonia
• Intervention / Treatment: Biological: Botulinum toxin type A

• Study Type: Interventional
• Enrollment (Actual): 516
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, A-8020
    • Krankenhaus der Barmherzigen Brüder
  • Grimmenstein, Austria, A-2240
    • NÖ LKH Grimmenstein-Hochegg
  • Innsbruck, Austria, A-6020
    • Univ.-Klinik für Neurologie
  • Linz, Austria, A-4014
    • Konventhospital der Barmherzigen Brüder
  • Linz, Austria, A-4020
    • O.Ö. Landes-Nervenklinik Wagner-Jauregg
• Germany
  • Aachen, Germany, 52074
    • Neurolog. Klinik des RWTH Aachen
  • Ahaus, Germany, 48683
    • Praxis für Anästhesiologie
  • Apolda, Germany, 99510
    • Praxis für Neurologie und Psychiatrie
  • Arnsdorf, Germany, 01477
    • Sächsisches Krankenhaus
  • Aschaffenburg, Germany, 63739
    • Praxis für Neurologie
  • Bad Oeynhausen, Germany, 32545
    • Klinikum für Rehabilitation
  • Bad Reichenhall, Germany, 83435
    • Praxis für Neurologie
  • Bayreuth, Germany, 95445
    • Krankenhaus Hohe Warte
  • Beelitz, Germany, 14547
    • Neurologische Rehabilitationsklinik
  • Bennewitz, Germany, 04828
    • NRZ Neurologisches Rehabilitationszentrum Leipzig
  • Berlin, Germany, 10178
    • Praxis für Neurologie
  • Berlin, Germany, 10713
    • Neurologisches Facharztzentrum am St.-Gertrauden-KH
  • Berlin, Germany, 10719
    • Praxis für Neurologie
  • Berlin, Germany, 12200
    • Universitätsklinikum Charité, Campus Benjamin Franklin
  • Berlin, Germany, 13353
    • Universitätsklinikum Charité, Campus Virchow-Klinikum
  • Berlin, Germany, 14050
    • Gemeinschaftspraxis für Neurologie
  • Berlin, Germany
    • Krankenhaus Henningsdorf
  • Bernburg, Germany, 06406
    • SALUS Fachkrankenhaus Bernburg
  • Bielefeld, Germany, 33617
    • Neurologische Klinik GILEAD im Evang. KH Bielefeld EVKB
  • Bochum, Germany, 44787
    • Praxis für Neurologie
  • Bochum, Germany, 44789
    • Berufsg. Kliniken Bergmannsheil
  • Bochum, Germany, 44791
    • St.-Josef-Hospital
  • Bonn, Germany, 53105
    • Medizinische Einrichtung Rhein. F.-Wilhelms-Universität Bonn
  • Bremen, Germany, 28325
    • Zentralkrankenhaus Bremen-Ost
  • Chemnitz, Germany, 09131
    • Klinikum Chemnitz gGmbH
  • Dachau, Germany, 85221
    • Praxis für Neurologie
  • Deggendorf, Germany, 94469
    • Bezirksklinikum Mainkofen
  • Dresden, Germany, 01307
    • Universitätsklinikum Carl Gustav Carus
  • Duisburg, Germany, 47259
    • Malteser Krankenhaus St. Anna
  • Düsseldorf, Germany, 40225
    • University Hospital, Neurology Clinic
  • Eberswalde, Germany, 16225
    • Landesklinik Eberswalde
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Erlangen, Germany, 91054
    • Uniklinik Erlangen
  • Essen, Germany, 45117
    • Alfried-Krupp-Krankenhaus
  • Essen, Germany, 45147
    • Universitätsklinik Essen
  • Freiberg, Germany, 09599
    • Kreiskrankenhaus Freiberg
  • Giessen, Germany, 35385
    • Zentrum für Neurologie
  • Giessen, Germany, 35392
    • Praxis für Neurologie und Psychiatrie
  • Gießen, Germany, 35390
    • Praxis für Neurologie
  • Großschweidnitz, Germany, '02708
    • Sächsisches Krankenhaus für Psychiatrie, Psychotherapie und Neurolgie
  • Günzburg, Germany, 89312
    • Bezirkskrankenhaus Günzburg
  • Hagen, Germany, 58091
    • Klinikum Ambrock
  • Hagen, Germany, 58099
    • Katholisches Krankenhaus Hagen
  • Halle, Germany, 06120
    • Städt. Krankenhaus Martha-Maria
  • Hamburg, Germany, 20249
    • Gemeinschaftspraxis für Neurologie
  • Hamburg, Germany, 22525
    • Praxis für Neurologie
  • Hannover, Germany
    • Neurologische Uniklinik
  • Hannover, Germany
    • Praxis für Neurologie
  • Homburg, Germany, 66421
    • Universitätskliniken des Saarlandes
  • Ilmenau, Germany, 98693
    • Gemeinschaftspraxis für Neurologie/Psychiatrie
  • Itzehoe, Germany, 25524
    • Praxis für Neurologie
  • Jena, Germany, 07743
    • Uniklinik Jena
  • Kaiserslautern, Germany, 67655
    • Westpfalz-Klinikum GmbH
  • Kiel, Germany, 24105
    • Universitätsklinikum Kiel
  • Koblenz, Germany, 56073
    • Kath. Klinikum/Brüderkrankenhaus
  • Koeln, Germany
    • Klinikum Koeln-Merheim
  • Landshut, Germany, 84028
    • Neurologische Praxis
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • Leipzig, Germany, 04155
    • Gemeinschaftspraxis für Neurologie/Psychiatrie
  • Leipzig, Germany, 04229
    • Gemeinschaftspraxis für Neurologie
  • Lemgo, Germany, 32657
    • Klinikum Lippe-Lemgo GmbH
  • Ludwigshafen, Germany, 67063
    • Klinikum der Stadt Ludwigshafen
  • Lübeck, Germany, 23562
    • Universitätsklinikum
  • Lüneburg, Germany, 21335
    • Gemeinschaftspraxis für Neurologie/Psychiatrie
  • Magdeburg, Germany, 39120
    • Universitätsklinikum
  • Mainz, Germany, 55131
    • Universitätsklinikum
  • Mannheim, Germany, 68167
    • Klinikum Mannheim
  • Mannheim, Germany, 68169
    • Praxis für Neurologie
  • Minden, Germany, 32427
    • Klinikum Minden
  • Mönchengladbach, Germany, 41063
    • Kliniken Maria Hilf GmbH
  • München, Germany, 81675
    • Klinikum Rechts der Isar
  • München, Germany, 80804
    • Neurologisches Krankenhaus München
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Neubrandenburg, Germany, 17033
    • Praxis für Neurologie und Nervenheilkunde
  • Nürnberg, Germany, 90471
    • Klinikum Nürnberg-Süd
  • Oldenburg, Germany, 26122
    • Evangelisches Krankenhaus Oldenburg
  • Ostfildern, Germany, 73760
    • Praxis für Neurologie und Psychiatrie
  • Paderborn, Germany, 33098
    • St. Vincenz-Krankenhaus GmbH
  • Potsdam, Germany, 14467
    • Klinikum Ernst von Bergmann
  • Potsdam, Germany, 11471
    • St.-Josefs-Krankenhaus
  • Ravensburg, Germany, 88214
    • Zentrum für Psychiatrie Weissenau
  • Recklinghausen, Germany, 45657
    • Knappschafts-Krankenhaus
  • Rostock, Germany, 18147
    • Universitätsklinikum
  • Rüdersdorf, Germany, 15562
    • Evang.-Freichkirchl. Krankenhaus
  • Schorndorf, Germany, 73614
    • Praxis für Neurologie
  • Schwedt/Oder, Germany, 16303
    • Klinikum Uckermark GmbH
  • Schwerin, Germany, 19055
    • HELIOS Kliniken Schwerin
  • Seesen, Germany, 38723
    • Asklepios Kliniken Schildautal
  • Singen, Germany, 78224
    • EMSA
  • Stadtroda, Germany, 07646
    • Landesfachkrankenhaus für Psychatrie und Neurologie
  • Stralsund, Germany, 18439
    • Praxis für Neurologie
  • Straubing, Germany, 94315
    • Neurologische Praxis
  • Teupitz, Germany, 15775
    • Landesklinik Teupitz
  • Tübingen, Germany, 72076
    • Zentrum für Neurologie und Hertie-Institut für Klinische Hirnforschung
  • Weiden, Germany, 92637
    • Klinikum Weiden
  • Wiesbaden, Germany, 65191
    • Stiftung Deutsche Klinik für Diagnostik
  • Wolfenbüttel, Germany, 38300
    • Gemeinschaftspraxis für Neurologie
  • Wuppertal, Germany, 42283
    • Klinikum Wuppertal
  • Würzburg, Germany, 97070
    • Universitätsklinikum Würzburg
  • Würzburg, Germany, 97070
    • Medizinisches Studienzentrum
  • Zwickau, Germany, 08060
    • Paracelsus Klinik

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• De novo patients with cervical dystonia
• Outpatient
• Patients to be of age 18 years or older
• Written informed consent to participate in the study

Exclusion Criteria:

• Pre-treatment of cervical dystonia with botulinum toxin
• Pre-treatment with botulinum toxin for any indication other than cervical dystonia within the past 12 months
• Pure retro- or antecollis
• Neurological or other diseases which may affect head and neck motor function or neuromuscular transmission, e.g. polyneuropathy with pareses, myasthenia, myopathy, motor neurone diseases, Bekhterev's disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Biological: Botulinum toxin type A; Active Drug: Botulinum type A toxin (Dysport®) 500 Units / 2.5 ml injected in muscles involved in cervical dystonia; Other Names: AbobotulinumtoxinA (Dysport®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Total Score of the Tsui Rating Scale (Patient in Sitting Position) at the First On-treatment Visit (Week 4 or Week 12)	The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0-9 points); Subscore B: duration of movement (values 1 or 2); Subscore C: severity and duration of shoulder elevation (range: 0-3 points); Subscore D: severity and duration of tremor (range: 0-4 points). The total score was calculated as follows: total score = subscores (A x B) + C + D. The total score ranges between 0 and 25 points. A high total score represents severe CD. The mean change in the total score of the Tsui rating scale (patient in the sitting position) between baseline (Week 0 visit) and the first on-treatment visit (Week 4 or Week 12 visit) is presented.	Baseline to Week 4 or Week 12 (up to 12 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Total Score of the Tsui Rating Scale (Patient in Sitting Position) Between Visit 1 (Week 0) and Visit 3 (Week 12)	The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0-9 points); Subscore B: duration of movement (values 1 or 2); Subscore C: severity and duration of shoulder elevation (range: 0-3 points); Subscore D: severity and duration of tremor (range: 0-4 points). The total score was calculated as follows: total score = subscores (A x B) + C + D. The total score ranges between 0 and 25 points. A high total score represents severe CD. The mean change in the total score of the Tsui rating scale (patient in the sitting position) between baseline (Week 0 visit) and the Week 12 visit is presented.	Baseline to Week 12
Change in the Total Score of the Tsui Rating Scale (Patient Walking) Between Baseline (Week 0) and Visit 2 (Week 4) and Visit 3 (Week 12)	The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0-9 points); Subscore B: duration of movement (values 1 or 2); Subscore C: severity and duration of shoulder elevation (range: 0-3 points); Subscore D: severity and duration of tremor (range: 0-4 points). The total score was calculated as follows: total score = subscores (A x B) + C + D. The total score ranges between 0 and 25 points. A high total score represents severe CD. The mean changes in the total score of the Tsui rating scale (patient walking) between baseline (Week 0 visit) and the Week 4 and Week 12 visits are presented.	Baseline to Week 4 and Week 12
Change in the 4 Subscores of the Tsui Rating Scale (Patient in the Sitting Position) Between Visit 1 (Week 0) and Visit 2 (Week 4) and Visit 3 (Week 12)	The Tsui rating scale measures severity and duration of head deviation, shoulder elevation and head tremor. This instrument is based on 4 subscores: Subscore A: amplitude of rotation, deflection (tilt) and ante- / retrocollis (range: 0-9 points); Subscore B: duration of movement (values 1 or 2); Subscore C: severity and duration of shoulder elevation (range: 0-3 points); Subscore D: severity and duration of tremor (range: 0-4 points). A higher score for each subscale represents severe CD symptoms. The total score was calculated as follows: total score = subscores (A x B) + C + D. The total score ranges between 0 and 25 points. A high total score represents severe CD. The mean changes in the subscores A to D of the Tsui rating scale (patient in the sitting position) between baseline (Week 0 visit) and the Week 4 and Week 12 visits are presented.	Baseline to Week 4 and Week 12
Change in the Craniocervical Dystonia Questionnaire (CDQ-24) Total Score and Subscores Between Visit 1 (Week 0) and Visit 2 (Week 4) and Visit 3 (Week 12)	The CDQ-24 is a disease-specific quality of life (QoL) instrument and was assessed at Visits 1 to 3. It consists of 24 items investigating problems in daily living skills related to CD. This instrument is based on 5 subscales: Stigma, Emotional well-being, Pain, Activities of daily living (ADL), Social/family life to which a number of the 24 items are assigned. There are five possible answers to each item representing increasing severity of impairment (scores 0 to 4). The total scores ranged from 0 to 96 (best to worst QoL). In order to obtain scores of the individual subscales, the total score of each subscale (sum of the individual item scores) was transformed linearly to a 0 to 100 scale (best to worst QoL). The mean changes in the CDQ-24 total score between baseline (Week 0 visit) and the Week 4 and Week 12 visits are presented.	Baseline to Week 4 and Week 12
Changes in the Items of the Patient Diary Based on Day-to-day Function and Activities, Pain and Duration of Pain Between Visit 1 (Week 0) and Visit 2 (Week 4) and Visit 3 (Week 12)	The weekly recorded patient diary consists of the three items: Day-to-Day Capacities and Activities, Pain and Duration of Pain. Each item was rated by the patient on an 11-point scale ranging from 0 = no problems at all to 10 = most severe problems (the actual wording is adapted to each item in question). The mean changes between the baseline (Week 0 visit) and the Week 4 and Week 12 visits are presented.	Baseline to Week 4 and Week 12
Categorical Changes in the Items of the Patient Diary Based on Day-to-day Function and Activities, Pain and Duration of Pain Between Visit 1 (Week 0) and Visit 2 (Week 4) and Visit 3 (Week 12)	The weekly recorded patient diary consists of the three items: Day-to-Day Capacities and Activities, Pain and Duration of Pain. Each item was rated by the patient on an 11-point scale ranging from 0 = no problems at all to 10 = most severe problems (the actual wording is adapted to each item in question). The following categorical changes between the baseline (Week 0 visit) and the Week 4 and Week 12 visits are presented: Improvement, No change and Deterioration.	Baseline to Week 4 and Week 12
Number of Patients Without Pain and/or With a Reduction in Pain Based on a Global Assessment of Pain by the Investigator and by the Patient at Visit 2 (Week 4) and Visit 3 (Week 12)	Global pain was assessed at Visit 2 (Week 4) and Visit 3 (Week 12); investigators and patients assessed change in global pain according to the following response categories: = no pain (anymore); = less pain; = no change; = more pain The numbers of patients falling under each of these categories as assessed by the investigator and patient at Weeks 4 and 12 are presented.	Week 4 visit and Week 12 visit
Global Assessment of Efficacy by the Investigator and by the Patient at Visit 2 (Week 4) and Visit 3 (Week 12)	At Visit 2 (Week 4) and Visit 3 (Week 12) investigators and patients assessed global efficacy of injection of 500 U Dysport® according to the following response categories: = very good; = good; = moderate; = insufficient The numbers of patients falling under each of these categories as assessed by the investigator and patient at Weeks 4 and 12 are presented.	Week 4 and Week 12

Collaborators and Investigators

• Sponsor: Ipsen

Publications and helpful links

General Publications

• Hefter H, Benecke R, Erbguth F, Jost W, Reichel G, Wissel J. An open-label cohort study of the improvement of quality of life and pain in de novo cervical dystonia patients after injections with 500 U botulinum toxin A (Dysport). BMJ Open. 2013 Apr 18;3(4):e001853. doi: 10.1136/bmjopen-2012-001853. Print 2013.
• Hefter H, Kupsch A, Mungersdorf M, Paus S, Stenner A, Jost W; Dysport Cervical Dystonia Study Group. A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis. BMJ Open. 2011 Jan 1;1(2):e000196. doi: 10.1136/bmjopen-2011-000196.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: March 13, 2007
• First Submitted That Met QC Criteria: March 13, 2007
• First Posted (Estimate): March 15, 2007

Study Record Updates

• Last Update Posted (Actual): March 30, 2023
• Last Update Submitted That Met QC Criteria: March 3, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Dysport, Cervical Dystonia
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Dystonia; Dystonic Disorders; Torticollis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Cholinergic Agents; Membrane Transport Modulators; Acetylcholine Release Inhibitors; Neuromuscular Agents; Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
• Other Study ID Numbers: A-94-52120-098; 2004-002086-20 (EudraCT Number)