Clinical trial NCT02207946: Botulinum Toxin A to Treat Arm Tremor
Official title: Prospective, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of the Efficacy and Safety of NT 201 in the Unilateral Treatment of Essential Tremor of the Upper Limb
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Essential Tremor of the Upper Limbs
Lead sponsor: Merz Pharmaceuticals GmbH
Sponsor class: INDUSTRY
First posted: 2014-08-04
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The objective of this study is to assess the efficacy and safety of a single, kinematic-analysis-based intramuscular injection of NT 201, compared with placebo, in moderate to marked essential tremor of the upper limb.


Eligibility criteria: Main Inclusion Criteria:

* Diagnosis of 'definite essential tremor' in accordance with modified TRIG criteria, as follows:

  * Bilateral postural tremor with or without kinetic tremor, involving hands and forearms, that is visible and persistent.
  * It is to be noted that:
  * Tremor of other body parts may be present in addition to upper limb tremor.
  * Bilateral tremor may be asymmetric.
  * Tremor is reported by patient to be persistent, although the amplitude may fluctuate.
* First onset of essential tremor at least 6 months before screening with stability of the tremor symptoms over 4 weeks and in the opinion of the investigator definite diagnosis of essential tremor.
* Moderate-to-marked upper-limb postural and/or kinetic tremor at wrist level, corresponding to Fahn-Tolosa-Marin upper-limb tremor rating of at least 2 categories (scale part C, items 16-23) in the limb to be treated between of 2 or higher.
* Visible tremor at wrist level in at least one of the four positions/tasks used in kinematic assessments
* Tremor deemed by the investigator to require a treatment with 30 - 200 U NT 201 for a treatment of up to three joints of the selected upper limb (wrist treatment mandatory).
* Stable concomitant anti-tremor medication and no clinically relevant findings in routine laboratory examinations.

Main Exclusion Criteria:

* Any neurological signs abnormal for the subject's age, other than the tremor itself and Froment's maneuver.
* Exposure to the following tremorogenic drugs: Lithium, Valproic acid, Amiodarone, typical and atypical neuroleptics. Exposure to other than the listed tremorogenic or potentially tremorogenic drugs is allowed only if, in the opinion of the investigator, this will not interfere with the study drug evaluation. In these cases, a stable medication should be reached 4 weeks before screening and intended for the time during the study drug evaluation.
* Trauma to the central nervous system or the nerves of the target limb within the three months preceding the onset of tremor.
* Evidence of psychogenic origins of tremor.
* Life habits (e.g. smoking, alcohol or substance abuse) prejudicial to study participation.
* Prior surgery to treat tremor
* Recent (16 weeks) treatment with any Botulinum toxin product for any reason.
* Relevant recent or planned surgery or other specified relevant treatments and/or concomitant disorders.

Primary outcomes:
measure: Change From Baseline to Week 4 in Maximum Angular Tremor Amplitude of the Wrist (Injected Limb)
timeFrame: Baseline up to Week 4
Secondary outcomes:
measure: Change From Baseline to Week 4 in Maximum Log-transformed Accelerometric Tremor Amplitude at Wrist Level (Injected Limb)
timeFrame: Baseline up to Week 4
measure: Change From Baseline to Week 4 in Fahn-Tolosa-Marin (FTM) Tremor Score in Injected Limb (Item 5 [Right Upper Extremity] or 6 [Left Upper Extremity])
timeFrame: Baseline up to Week 4
measure: Change From Baseline to Week 4 in FTM Motor Performance Score (Items 11-15)
timeFrame: Baseline up to Week 4
measure: Participant's Global Impression of Change Scale (GICS) at Week 4
timeFrame: Week 4
measure: Investigator's Global Impression of Change Scale (GICS) at Week 4
timeFrame: Week 4
Other outcomes:
Locations:
city: New York
country: United States
facility: Merz Investigational Site #0010191
state: New York
city: Winnipeg
country: Canada
facility: Merz Investigational Site #0010317
state: Manitoba
city: Halifax
country: Canada
facility: Merz Investigational Site #0010089
state: Nova Scotia
city: Toronto
country: Canada
facility: Merz Investigational Site #0010078
state: Ontario
city: Toronto
country: Canada
facility: Merz Investigational Site #0010305/1
state: Ontario
city: Toronto
country: Canada
facility: Merz Investigational Site #0010305/2
state: Ontario
Study officials:
affiliation: Merz Pharmaceuticals GmbH
name: Merz Medical Expert
role: STUDY_DIRECTOR
References:
citation: Jog M, Lee J, Scheschonka A, Chen R, Ismail F, Boulias C, Hobson D, King D, Althaus M, Simon O, Dersch H, Frucht S, Simpson DM. Tolerability and Efficacy of Customized IncobotulinumtoxinA Injections for Essential Tremor: A Randomized, Double-Blind, Placebo-Controlled Study. Toxins (Basel). 2020 Dec 20;12(12):807. doi: 10.3390/toxins12120807.