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Arm SpasticityPhase 3NMJNCT01682148

Comparing Lower-concentration Dysport Treatment Targeted to the Neuromuscular Junction With Current Clinical Practice

A Phase 3 study testing Botulinum toxin type A in people with Arm Spasticity, run by Ipsen at 23 sites in 4 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Arm Spasticity
What is being tested?
Botulinum toxin type A
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
100 participants
Where
23 sitesin 4 countries
Study dates
Sep 2012to Mar 2015
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
Show all 16Show fewer
  • 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.
  • Had abnormal Baseline findings, any other medical condition(s) or laboratory findings that, in the opinion of the investigator, might have jeopardised the subject's safety or decreased the chance of obtaining satisfactory data needed to achieve the objective(s) of the study.

Trial locations and contacts

23 sites in 4 countries.

23 sites in 4 countries

Sweden12 sites

  • Mälarsjukhuset MSE

    Eskilstuna, 631-88

  • Sahlgrenska University Hospital

    Gothenburg

  • Hallands Sjukhus, Neurology Clinic

    Halmstad, 30185

  • Sundsvall-Härnösand, Rehabilitation Medicine

    Härnösand, 87182

  • Nyköpings Lasarett,

    Nyköping, 61185

  • Örnsköldsviks Sjukhus, Neurology Clinic

    Örnsköldsvik, 891 89

  • Östersunds Rehabilitation Center

    Östersund, 83102

  • Neurorehab Sävar

    Sävar, 91831

  • Neurology Clinic Stockholm

    Stockholm, 114 33

  • Danderyds Hospital,

    Stockholm, 18288

  • Rehabilitation Center Gotland

    Visby, 62184

  • Ystad Lasarett

    Ystad, 27133

Other trials in Sweden

Denmark7 sites

  • Aalborg Sygehus Nord

    Aalborg, 9000

  • Glostrup Hospital

    Glostrup Municipality, 2600

  • Regionshospitalet Hammel

    Hammel, 8450

  • Bispebjerg Hospital

    København NV, 2400

  • Roskilde Hospital

    Roskilde, 4000

  • Vejle Hospital

    Vejle, 7100

  • Regionshopsitalet Viborg

    Viborg, 8800

Other trials in Denmark

Finland2 sites

  • North Karelia Central Hospital

    Joensuu, 80210

  • Central Hospital of Central Finland

    Jyväskylä, 40503

Other trials in Finland

Norway2 sites

  • Haukeland University Hospital

    Bergen, 5021

  • Sykehuset Telemark HF

    Skien, , 3700

Other trials in Norway

About this study

Official title: A Phase III Prospective, Multi-center, Randomised, Evaluator-blinded Study to Compare Neuromuscular Junction (NMJ) Targeted Technique for Dysport Injections in Upper Limb Spasticity Post Stroke or Traumatic Brain Injury to the Technique Used in Current Clinical Practice

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.

Read the detailed description

This was a randomised, evaluator-blinded, comparative, parallel group, multicentre study, conducted in four countries (Denmark, Finland, Norway and Sweden). For each subject, the primary efficacy assessments using MAS were performed by the same blinded evaluator, and every effort was made at each site to ensure that the MAS evaluator was the same person throughout the study. Dysport doses were to follow clinical practice for subjects suffering from upper limb spasticity position pattern type 1, 3 or 4 post stroke or traumatic brain injury.

The hypothesis for this study was that one low-concentration botulinum neurotoxin type A (BoNT-A) injection per muscle, centrally located in the area/band of the NMJ zones, would spread to and block the surrounding NMJ zones and be as effective as the technique used today in clinical practice. The possibility to reduce the number of injection points would decrease the risk of injection discomfort, pain and injection site bleeding for the patient. A simplified injection technique with one injection per muscle and in a defined location would also benefit physicians.

At Baseline (Visit 1), subjects were randomised to one of two treatment groups:

  • Group 1: Current clinical practice technique and high-concentration dilution: Dysport 300 U/mL.
  • Group 2: NMJ targeted technique and low-concentration dilution: Dysport 100 U/mL.

Each subject visited the clinic on at least three occasions:

  • Baseline (Visit 1): Screening, randomisation and Dysport treatment.
  • Week 4 (Visit 2): Treatment follow-up, 4 weeks after Dysport treatment.
  • Week 12 (Visit 3): Treatment and study follow-up, 12 weeks after Dysport treatment.

For subjects not receiving any post study BoNT-A injection at Week 12 due to remaining treatment effect, an extra visit (Visit 4) for study follow-up was to take place at the next routine visit planned for a new BoNT-A injection, at the latest 24 weeks post study injection.

The duration of each subject's study period was at a minimum 12 weeks and maximum 24 weeks. The overall duration of the study was planned to be approximately 36 months.

Conditions
Arm Spasticity
Keywords
Dysport, arm spasticity, Modified Ashworth Scale, neuromuscular junction, Botulinum toxin, upper limb spasticity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01682148
Study groupRoleWhat they receive
NMJ TargetedExperimentalNMJ 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.
Receives: Biological: Botulinum toxin type A
Current Clinical PracticeActive comparatorCurrent 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.
Receives: Biological: Botulinum toxin type A

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to Week 4

Secondary outcomes (7)

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

    Increased muscle tone in elbow flexors was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension).

    Measured: Baseline to Week 12

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

    A clinically relevant change was one level decrease on the MAS scale. Subjects meeting the defined decrease at Week 12 were considered as responders.

    Measured: Baseline to Week 12

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

    Pain assessment using the VAS. The VAS was a 10 cm straight horizontal line scoring scale. Score range on VAS was from 0 to 10 where 0 indicated no pain and 10 indicated worst pain imaginable.

    Measured: Baseline, Week 4 and Week 12

  4. Injection Site Pain Measured by VAS at Day 1.

    Pain assessment using the VAS. The VAS was a 100 mm straight horizontal line scoring scale. Score range on VAS was from 0 to 100 where 0 indicated no pain and 100 indicated worst pain imaginable.

    Measured: Baseline

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

    At Baseline, an agreed primary goal related to elbow flexion in one of the following categories was determined: active function, impairment, involuntary movement, mobility, pain passive function or other. Each goal was usually rated -1, unless the subject was as bad as he/she could be in that particular goal area, in which case the Baseline score was -2. The evaluator rated the outcome score at Week 4 or Week 12, depending on the time point defined at the baseline visit (Visit 1), using the GAS five-point scale (-2, -1, 0, +1 and +2).

    Measured: Up to Week 12

  6. Subject Global Evaluation of Treatment Effect

    Comparison of treatment effect between previous (prestudy) and study treatment cycles assessed by the subject at the end of study (Week 12 up to Week 24 (Visit 3 or Visit 4)). Categorised as follows: Much worse / Worse / Same / Better / Much better.

    Measured: Up to Week 24

  7. Investigator Preference of Injection Technique

    When all patients at the site had completed the study (last subject last visit) a global assessment of the injection technique was to be made by the Investigators. The following question was answered: "Based on your experience during this study, which injection technique do you prefer?"

    Measured: Following last visit of the last subject at each site

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2012 (estimated)
  2. Study startSep 2012
  3. Primary completionMar 2015
  4. Study completionMar 2015

Why it stopped: The study was terminated early due to slow recruitment.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
100 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01682148
Sponsor's protocol ID
A-99-52120-162
Other IDs
2011-005375-16
Acronym
NMJ
Status last verified
Sep 2022
First submitted
6 Sep 2012
Last updated
27 Sep 2022
Data monitoring committee
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 31061021

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Botulinum toxin type A in people with Arm Spasticity, run by Ipsen at 23 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 23 sites in Sweden, Denmark, Finland, Norway. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline for Elbow Flexors Muscle Tone as Measured by the Modified Ashworth Scale (MAS) at Week 4 (time frame: Baseline to Week 4). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01682148, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.

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