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

Cervical Dystonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00447772
• Other study ID #: A-94-52120-098
• Secondary ID: 2004-002086-20
• Status: Completed
• Phase: Phase 3
• Start date: October 2004
• Est. completion date: April 2008

Study information

• Verified date: March 2023
• Source: Ipsen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 516
• Est. completion date: April 2008
• Est. primary completion date: February 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cervical Dystonia
• Dystonia
• Dystonic Disorders
• Torticollis

Intervention

Biological:
• Botulinum toxin type A
Active Drug: Botulinum type A toxin (Dysport®) 500 Units / 2.5 ml injected in muscles involved in cervical dystonia

Locations

Country	Name	City	State
Austria	Krankenhaus der Barmherzigen Brüder	Graz
Austria	NÖ LKH Grimmenstein-Hochegg	Grimmenstein
Austria	Univ.-Klinik für Neurologie	Innsbruck
Austria	Konventhospital der Barmherzigen Brüder	Linz
Austria	O.Ö. Landes-Nervenklinik Wagner-Jauregg	Linz
Germany	Neurolog. Klinik des RWTH Aachen	Aachen
Germany	Praxis für Anästhesiologie	Ahaus
Germany	Praxis für Neurologie und Psychiatrie	Apolda
Germany	Sächsisches Krankenhaus	Arnsdorf
Germany	Praxis für Neurologie	Aschaffenburg
Germany	Klinikum für Rehabilitation	Bad Oeynhausen
Germany	Praxis für Neurologie	Bad Reichenhall
Germany	Krankenhaus Hohe Warte	Bayreuth
Germany	Neurologische Rehabilitationsklinik	Beelitz
Germany	NRZ Neurologisches Rehabilitationszentrum Leipzig	Bennewitz
Germany	Gemeinschaftspraxis für Neurologie	Berlin
Germany	Krankenhaus Henningsdorf	Berlin
Germany	Neurologisches Facharztzentrum am St.-Gertrauden-KH	Berlin
Germany	Praxis für Neurologie	Berlin
Germany	Praxis für Neurologie	Berlin
Germany	Universitätsklinikum Charité, Campus Benjamin Franklin	Berlin
Germany	Universitätsklinikum Charité, Campus Virchow-Klinikum	Berlin
Germany	SALUS Fachkrankenhaus Bernburg	Bernburg
Germany	Neurologische Klinik GILEAD im Evang. KH Bielefeld EVKB	Bielefeld
Germany	Berufsg. Kliniken Bergmannsheil	Bochum
Germany	Praxis für Neurologie	Bochum
Germany	St.-Josef-Hospital	Bochum
Germany	Medizinische Einrichtung Rhein. F.-Wilhelms-Universität Bonn	Bonn
Germany	Zentralkrankenhaus Bremen-Ost	Bremen
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	Praxis für Neurologie	Dachau
Germany	Bezirksklinikum Mainkofen	Deggendorf
Germany	Universitätsklinikum Carl Gustav Carus	Dresden
Germany	Malteser Krankenhaus St. Anna	Duisburg
Germany	University Hospital, Neurology Clinic	Düsseldorf
Germany	Landesklinik Eberswalde	Eberswalde
Germany	HELIOS Klinikum Erfurt	Erfurt
Germany	Uniklinik Erlangen	Erlangen
Germany	Alfried-Krupp-Krankenhaus	Essen
Germany	Universitätsklinik Essen	Essen
Germany	Kreiskrankenhaus Freiberg	Freiberg
Germany	Praxis für Neurologie und Psychiatrie	Giessen
Germany	Zentrum für Neurologie	Giessen
Germany	Praxis für Neurologie	Gießen
Germany	Sächsisches Krankenhaus für Psychiatrie, Psychotherapie und Neurolgie	Großschweidnitz
Germany	Bezirkskrankenhaus Günzburg	Günzburg
Germany	Katholisches Krankenhaus Hagen	Hagen
Germany	Klinikum Ambrock	Hagen
Germany	Städt. Krankenhaus Martha-Maria	Halle
Germany	Gemeinschaftspraxis für Neurologie	Hamburg
Germany	Praxis für Neurologie	Hamburg
Germany	Neurologische Uniklinik	Hannover
Germany	Praxis für Neurologie	Hannover
Germany	Universitätskliniken des Saarlandes	Homburg
Germany	Gemeinschaftspraxis für Neurologie/Psychiatrie	Ilmenau
Germany	Praxis für Neurologie	Itzehoe
Germany	Uniklinik Jena	Jena
Germany	Westpfalz-Klinikum GmbH	Kaiserslautern
Germany	Universitätsklinikum Kiel	Kiel
Germany	Kath. Klinikum/Brüderkrankenhaus	Koblenz
Germany	Klinikum Koeln-Merheim	Koeln
Germany	Neurologische Praxis	Landshut
Germany	Gemeinschaftspraxis für Neurologie	Leipzig
Germany	Gemeinschaftspraxis für Neurologie/Psychiatrie	Leipzig
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Klinikum Lippe-Lemgo GmbH	Lemgo
Germany	Universitätsklinikum	Lübeck
Germany	Klinikum der Stadt Ludwigshafen	Ludwigshafen
Germany	Gemeinschaftspraxis für Neurologie/Psychiatrie	Lüneburg
Germany	Universitätsklinikum	Magdeburg
Germany	Universitätsklinikum	Mainz
Germany	Klinikum Mannheim	Mannheim
Germany	Praxis für Neurologie	Mannheim
Germany	Klinikum Minden	Minden
Germany	Kliniken Maria Hilf GmbH	Mönchengladbach
Germany	Klinikum rechts der Isar	München
Germany	Neurologisches Krankenhaus München	München
Germany	Universitätsklinikum Münster	Münster
Germany	Praxis für Neurologie und Nervenheilkunde	Neubrandenburg
Germany	Klinikum Nürnberg-Süd	Nürnberg
Germany	Evangelisches Krankenhaus Oldenburg	Oldenburg
Germany	Praxis für Neurologie und Psychiatrie	Ostfildern
Germany	St. Vincenz-Krankenhaus GmbH	Paderborn
Germany	Klinikum Ernst von Bergmann	Potsdam
Germany	St.-Josefs-Krankenhaus	Potsdam
Germany	Zentrum für Psychiatrie Weissenau	Ravensburg
Germany	Knappschafts-Krankenhaus	Recklinghausen
Germany	Universitätsklinikum	Rostock
Germany	Evang.-Freichkirchl. Krankenhaus	Rüdersdorf
Germany	Praxis für Neurologie	Schorndorf
Germany	Klinikum Uckermark GmbH	Schwedt/Oder
Germany	HELIOS Kliniken Schwerin	Schwerin
Germany	Asklepios Kliniken Schildautal	Seesen
Germany	EMSA	Singen
Germany	Landesfachkrankenhaus für Psychatrie und Neurologie	Stadtroda
Germany	Praxis für Neurologie	Stralsund
Germany	Neurologische Praxis	Straubing
Germany	Landesklinik Teupitz	Teupitz
Germany	Zentrum für Neurologie und Hertie-Institut für Klinische Hirnforschung	Tübingen
Germany	Klinikum Weiden	Weiden
Germany	Stiftung Deutsche Klinik für Diagnostik	Wiesbaden
Germany	Gemeinschaftspraxis für Neurologie	Wolfenbüttel
Germany	Klinikum Wuppertal	Wuppertal
Germany	Medizinisches Studienzentrum	Würzburg
Germany	Universitätsklinikum Würzburg	Würzburg
Germany	Paracelsus Klinik	Zwickau

Sponsors (1)

Lead Sponsor	Collaborator
Ipsen

Countries where clinical trial is conducted

Austria,  Germany, 

References & Publications (2)

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 — View Citation

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-20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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