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IncobotulinumtoxinA (Xeomin) to Treat Focal Hand Dystonia

Phase 3
Recruiting
Conditions
Focal Hand Dystonia
Interventions
Drug: Placebo - Concentrate
Registration Number
NCT03977493
Lead Sponsor
Alain Kaelin
Brief Summary

This study is a multicenter, double-blind, randomized placebo controlled, parallel group, superiority trial in order to test the superiority of intramuscular injections of IncobotulinumtoxinA against placebo using a 1:1 allocation ratio.

Detailed Description

After a baseline evaluation, each patient will receive a first injection of IncobotulinumtoxinA or placebo (50:50 randomization) in a double blinding setting. Assessment of the Focal hand dystonia (FHD) will be done at each site by an investigator blinded to the treatment.

A first evaluation of the efficacy will be performed after 6 weeks. After 6 weeks, patients unsatisfied with treatment and wishing to continue the treatment will receive an injection of IncobotulinumtoxinA regardless of the treatment arm they were initially assigned to at baseline. These patients will subsequently be excluded from the study.

A second assessment will be performed after 12 weeks (only for patients not receiving a second injection of IncobotulinumtoxinA at week 6).

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
48
Inclusion Criteria
  • Informed Consent as documented by signature
  • Age ≥ 18 years
  • Focal hand dystonia (FHD). Diagnosis must be made by a neurologist specialized in movement disorder (at least 2 years specific training, all partners listed have at least 2 years training)
  • Both idiopathic and secondary FHD are allowed
  • Both drug naive subjects and subjects previously treated with other BoNT-A will be included
  • Patients must be willing and able to comply with the study procedures
  • Female patients of childbearing potential must agree to use an effective method of contraception during the treatment period
Exclusion Criteria
  • Presence of spasticity, or other central sensorimotor lesion of motor system other than dystonia in the affected limb
  • Peripheral nerve lesion (diagnosis either clinical or electrophysiological) in the affected limb, for example with a muscle weakness at baseline
  • Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to BoNT-A toxins including IncobotulinumtoxinA
  • Doses and schedules of any ongoing treatment with potential confounding drugs such as muscle relaxants (for example Tolperison, Tizinadid, Baclofen, Mestinon, Dantrolen), benzodiazepine, neuroleptics or antidepressants have to be kept unchanged throughout the study and no changes should be made between the first trial injection and the end of study visit at week 12.
  • Previous treatment with other BoNT-A less than 3 months before the inclusion in this study
  • Women who are pregnant or breast feeding,
  • Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
  • Participation in another study with investigational drug within the 30 days preceding and during the present study
  • Previous enrolment into the current study
  • Enrolment of the investigator, his/her family members, employees and other dependent persons
  • Severe depression (>29 as measured with the Beck Depression Inventory, see Appendix 8) or other relevant psychiatric disorder
  • INR > 2 on the day of injection if the patient is anticoagulated. If INR > 2, the study injection will be delayed until the return to a safer INR.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo concentratePlacebo - ConcentrateIntramuscular Placebo injection under guidance (EMG and/or sonographic monitoring), in each muscle (max. 5 forearm- and/or hand muscles).
Xeomin®XeominIntramuscular IncobotulinumtoxinA (Xeomin®) injection under guidance (EMG and/or sonographic monitoring), 2.5 to 40 U in each muscle (max. 5 forearm- and/or hand muscles).
Primary Outcome Measures
NameTimeMethod
Evaluation of the efficacy of IncobotulinumtoxinA on focal hand dystonia (FHD)6 weeks

To evaluate patient's subjective impairment due to FHD on VAS for handwriting. The VAS for handwriting is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates the worst possible situation and 10 the best possible situation.

Secondary Outcome Measures
NameTimeMethod
Evaluation of the effect of IncobotulinumtoxinA on writing pressure6 and 12 weeks

To measure the change in writing pressure by using a pressure sensitive-tablet. Writing Movement pressure will be measured in Pascal.

Evaluation of the effect of IncobotulinumtoxinA on disease improvement6 and 12 weeks

To measure the change in the physician's clinical evaluation of the disease by using the CGI-improvement scale. The CGI-improvement scale ranges from 0 to 4 (none, minimal, mild, moderate, excellent).

Evaluation of the effect of IncobotulinumtoxinA on writing speed6 and 12 weeks

To measure the change in writing speed by using a pressure sensitive-tablet. Writing movement speed will be measured in seconds.

Evaluation of the effect of IncobotulinumtoxinA on muscle strength6 and 12 weeks

To measure the change in muscle strength by using the Medical Research Council Scale for Muscle strength. The patient's effort is graded on a scale of 0 (normal muscle) to 5 (no movement).

Evaluation of the responders to IncobotulinumtoxinA treatment6 and 12 weeks

Number of patients showing an improvement of FHD by ≥ 1 points over baseline

Evaluation of the effect of IncobotulinumtoxinA on FHD symptoms severity6 and 12 weeks

To measure change in symptoms severity by using the Symptom Severity Scale (SSS). Total SSS score ranges from 10 (best possible) to 43 (worst possible).

Evaluation of the effect of IncobotulinumtoxinA on functional status6 and 12 weeks

To measure change in functional status by using the Functional Status Scale (FSS). Total FSS score ranges from 0 (best possible) to 40 (worst possible).

Evaluation of the overall satisfaction of the patients following IncobotulinumtoxinA treatment6 weeks

Patients will answer the following two questions: a) Considering all advantages and disadvantages of this treatment, is the improvement such that you wish to continue this treatment or not? Yes/No b) Do you think that you would need an injection of IncobotulinumtoxinA today? Yes/No

Need of re-injection6 weeks

The physician will judge about whether an injection with IncobotulinumtoxinA is recommended or not (Yes/No)

Safety outcomes: adverse events6 and 12 weeks

Incidence and severity of adverse reactions (mild, moderate, severe).

Evaluation of the efficacy of IncobotulinumtoxinA on FHD12 weeks

To evaluate patient's subjective impairment due to FHD on VAS for handwriting. The VAS for handwriting is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates the worst possible situation and 10 the best possible situation.

Evaluation of the effect of IncobotulinumtoxinA on writer's cramp improvement6 and 12 weeks

To measure the change in writer's cramp measured by the Writer's Cramp Rating Scale (WCRS) - only part A. Total WCRS score ranges from 0 (no improvement) to 28 (marked improvement).

Safety outcomes: pain6 and 12 weeks

Pain assessed by VAS scale. The VAS for pain is a self-assessment scale drawn by the patients on a 10-cm line, on which 0 indicates no pain and 10 an extreme amount of pain.

Safety outcomes: weakness6 and 12 weeks

Weakness assessed by using the CGI-side effect scale and CGI-weakness scale. CGI-side effect scale ranges from 0 to 3 (no, mild, marked, severe side effects). CGI-weakness assessment scale ranges from 0 to 4 (none, \<25%, 26-50%, 51-75%, 76-100% reduction in normal strength).

Evaluation of the effect of IncobotulinumtoxinA on depressive symptoms6 and 12 weeks

To measure the change in depressive symptoms by using the Beck Depression Inventory (BDI). Total BDI score ranges from 0 to 63 with scores \> 29 indicating severe depression and \> 40 extreme depression.

Trial Locations

Locations (5)

Inselspital - University Hospital Berne

🇨🇭

Berne, Switzerland

USZ- Univerity Hospital Zurich

🇨🇭

Zurich, Switzerland

Neurocentro della Svizzera Italiana

🇨🇭

Lugano, Switzerland

Centre hospitalier universitaire vaudois (CHUV)

🇨🇭

Lausanne, Switzerland

Neurocenter of St. Gallen

🇨🇭

St.Gallen, Switzerland

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