NCT01682148

Brief Summary

The aim of the study was to compare Dysport treatment results (as assessed by Modified Ashworth Scale (MAS) in the elbow joint 4 weeks post treatment) following two treatment techniques: the current clinical practice injection technique using high-concentration dilution (300 U/mL Dysport) versus the neuromuscular junction (NMJ)-targeted injection technique using low-concentration dilution (100 U/mL Dysport). The hypothesis was that one high-volume, low-concentration injection located centrally in the area/band of the NMJ zones would be as effective as the technique used in current medical practice.

Trial Health

60
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
100

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Sep 2012

Geographic Reach
4 countries

23 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2012

Completed
5 days until next milestone

First Submitted

Initial submission to the registry

September 6, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

September 10, 2012

Completed
2.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2015

Completed
4 years until next milestone

Results Posted

Study results publicly available

February 18, 2019

Completed
Last Updated

September 27, 2022

Status Verified

September 1, 2022

Enrollment Period

2.5 years

First QC Date

September 6, 2012

Results QC Date

December 28, 2016

Last Update Submit

September 15, 2022

Conditions

Keywords

Dysportarm spasticityModified Ashworth Scaleneuromuscular junctionBotulinum toxinupper limb spasticity

Outcome Measures

Primary Outcomes (1)

  • Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4

    A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 4 were considered as responders in the primary efficacy analysis.

    Baseline to Week 4

Secondary Outcomes (7)

  • Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 and Week 12

    Baseline to Week 12

  • Change From Baseline for Elbow Flexors Muscle Tone as Measured by the MAS at Week 12

    Baseline to Week 12

  • Change From Baseline of Spasticity Related Pain Measured by Visual Analogue Scale (VAS), Assessed by the Subject

    Baseline, Week 4 and Week 12

  • Injection Site Pain Measured by VAS at Day 1.

    Baseline

  • Achievement of the Primary Goal Measured by Goal Attainment Scale (GAS)

    Up to Week 12

  • +2 more secondary outcomes

Study Arms (2)

NMJ Targeted

EXPERIMENTAL

NMJ targeted technique and low-concentration dilution (Dysport 100 U/mL). The same number and sites of injections/deposits per muscle were given as per prestudy. With a Dysport dilution of 300 U/mL the volume to be injected varied between 0.1 mL and 0.7 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.

Biological: Botulinum toxin type A

Current Clinical Practice

ACTIVE COMPARATOR

Current clinical practice technique and high-concentration dilution (Dysport 300 U/mL). A single injection per muscle was given in the midline of the band of NMJ zones. With a Dysport dilution of 100 U/mL the volume to be injected varied between 0.4 mL and 2.0 mL per muscle. The dose and the choice of muscles involved in the elbow flexion were the same as for the last prestudy treatment.

Biological: Botulinum toxin type A

Interventions

Also known as: AbobotulinumtoxinA (Dysport®)
Current Clinical PracticeNMJ Targeted

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Provision of written informed consent prior to any study related procedures.
  • Subjects male or female, aged 18 years or older.
  • Upper limb spasticity post stroke or traumatic brain injury.
  • Spasticity position pattern type 1, 3 or 4.
  • Elbow flexor muscles spasticity MAS 2 to 3.
  • At least 2 consecutive previous treatment cycles of BoNT-A for current diagnosis.
  • The latest treatment cycle demonstrating good treatment efficacy where the Dysport dose administered was considered to be adequate according to Investigator judgement.
  • Need of the same treatment modality in muscle (m.) brachialis, m. biceps brachii, m. brachioradialis, m. flexor carpi ulnaris, m. flexor carpi radialis as the previous treatment cycle.
  • Last BoNT-A treatment 12-24 weeks ago.

You may not qualify if:

  • Poor response to BoNT-A treatment, according to Investigator.
  • Need of Dysport doses \>800 U in the upper limb.
  • Concomitant treatment with BoNT-A for other indications than spasticity.
  • Any elbow flexor contracture prohibiting MAS evaluation and/or elbow flexion improvement of at least 1 step on the MAS.
  • Cutaneous or joint inflammation in the affected upper limb.
  • Was likely to start other spasticity treatment during the study.
  • Was likely to start physiotherapy treatment during the study.
  • Other ongoing neurological disorder (e.g., myasthenia gravis).
  • History of dysphagia or aspiration.
  • Use of agents interfering with neuromuscular transmission (e.g., aminoglycosides).
  • Treated with an investigational medicinal product within 30 days before start of the study.
  • Known sensitivity to BoNT-A or any components of Dysport.
  • Was at risk of pregnancy or was lactating. Females of childbearing potential must have provided a negative pregnancy test (urinary human chorionic gonadotropin (U-hCG)) at Visit 1 and must have been using adequate contraception. Non-childbearing potential was defined as post-menopause for at least one year, surgical sterilisation or hysterectomy at least three months before the start of the study.
  • Had a history of, or known current, problems with alcohol or drug abuse.
  • Had a mental condition rendering the subject unable to understand the nature, scope and possible consequences of the study, and/or evidence of an uncooperative attitude.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (23)

Aalborg Sygehus Nord

Aalborg, 9000, Denmark

Location

Glostrup Hospital

Glostrup Municipality, 2600, Denmark

Location

Regionshospitalet Hammel

Hammel, 8450, Denmark

Location

Bispebjerg Hospital

København NV, 2400, Denmark

Location

Roskilde Hospital

Roskilde, 4000, Denmark

Location

Vejle Hospital

Vejle, 7100, Denmark

Location

Regionshopsitalet Viborg

Viborg, 8800, Denmark

Location

North Karelia Central Hospital

Joensuu, 80210, Finland

Location

Central Hospital of Central Finland

Jyväskylä, 40503, Finland

Location

Haukeland University Hospital

Bergen, 5021, Norway

Location

Sykehuset Telemark HF

Skien, , 3700, Norway

Location

Mälarsjukhuset MSE

Eskilstuna, 631-88, Sweden

Location

Sahlgrenska University Hospital

Gothenburg, Sweden

Location

Hallands Sjukhus, Neurology Clinic

Halmstad, 30185, Sweden

Location

Sundsvall-Härnösand, Rehabilitation Medicine

Härnösand, 87182, Sweden

Location

Nyköpings Lasarett,

Nyköping, 61185, Sweden

Location

Örnsköldsviks Sjukhus, Neurology Clinic

Örnsköldsvik, 891 89, Sweden

Location

Östersunds Rehabilitation Center

Östersund, 83102, Sweden

Location

Neurorehab Sävar

Sävar, 91831, Sweden

Location

Neurology Clinic Stockholm

Stockholm, 114 33, Sweden

Location

Danderyds Hospital,

Stockholm, 18288, Sweden

Location

Rehabilitation Center Gotland

Visby, 62184, Sweden

Location

Ystad Lasarett

Ystad, 27133, Sweden

Location

Related Publications (1)

  • Rekand T, Biering-Sorensen B, He J, Vilholm OJ, Christensen PB, Ulfarsson T, Belusa R, Strom T, Myrenfors P, Maisonobe P, Dalager T. Botulinum toxin treatment of spasticity targeted to muscle endplates: an international, randomised, evaluator-blinded study comparing two different botulinum toxin injection strategies for the treatment of upper limb spasticity. BMJ Open. 2019 May 5;9(5):e024340. doi: 10.1136/bmjopen-2018-024340.

MeSH Terms

Interventions

Botulinum Toxins, Type AabobotulinumtoxinA

Intervention Hierarchy (Ancestors)

Botulinum ToxinsMetalloendopeptidasesEndopeptidasesPeptide HydrolasesHydrolasesEnzymesEnzymes and CoenzymesMetalloproteasesBacterial ProteinsProteinsAmino Acids, Peptides, and ProteinsBacterial ToxinsToxins, BiologicalBiological Factors

Limitations and Caveats

Due to slow recruitment, the study was terminated early. Therefore, fewer subjects than planned were enrolled.

Results Point of Contact

Title
Medical Director, Neurology
Organization
Ipsen

Study Officials

  • Ipsen Medical Director

    Ipsen

    STUDY DIRECTOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
OTHER
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 6, 2012

First Posted

September 10, 2012

Study Start

September 1, 2012

Primary Completion

March 1, 2015

Study Completion

March 1, 2015

Last Updated

September 27, 2022

Results First Posted

February 18, 2019

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will share

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of study participants. Any requests should be submitted to www.vivli.org for assessment by an independent scientific review board.

Time Frame
Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and EU or after the primary manuscript describing the results has been accepted for publication, whichever is later.
Access Criteria
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
More information

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