Back to resultsStudy to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression (ONTIME Pilot)
Primary Purpose
Stroke, Upper Limb Spasticity
Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
Botulinum toxin type A
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Stroke
Eligibility Criteria
Inclusion Criteria:
- 2 to 12 weeks after first ever stroke according to the World Health Organisation criteria (previous transient ischaemic attack or clinically silent infarct on computerised tomography (CT)/magnetic resonance imaging (MRI) are not counted as previous stroke)
- Stroke confirmed by CT/MRI scan and classified as ischaemic/haemorrhagic stroke
Presence of spasticity:
- either symptomatic, based on symptomatic spasticity criteria (i.e. at least one of the following items: impacted passive/active function, involuntary movements, or pain ≥4 on a numeric pain rating scale [NPRS]), in addition to increased muscle tone [Modified Ashworth Scale, MAS ≥2])
- or only increased muscle tone (MAS≥2)
Exclusion Criteria:
- Neuromuscular junction (NMJ) diseases, or any other neurological disorders (including prior local joint, tendon, and intrinsic muscle disorders) that could potentially interfere with assessment of spasticity in the primary targeted muscle group selected by the Investigator and in agreement with the subject
- Currently receiving drugs affecting NMJ transmission e.g. aminoglycosides, aminoquinolines, cyclosporine, D penicillamine
- Previous surgery of the affected muscles/ ligaments/tendons
- Severe comorbidities (e.g. congestive heart failure, myocardial infarction, multiple organ failure, hepatic renal failures, severe infections)
Sites / Locations
- Neurology Laboratory -University Malaya Medical Centre
- Center for Neurodiagnostic and Therapeutic Services Metropolitan Medical Center
- TTSH Rehabilitation Centre Ang Mo Kio Community Hospital
- Department of rehabilitation Medicine Faculty of medicine Siriraj Hospital, Madihol University Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Treatment group
Placebo Group
Arm Description
Dysport® 500U intramuscular injection
Placebo intramuscular injection
Outcomes
Primary Outcome Measures
Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms
The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL:
A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain])
An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact])
An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale
An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb.
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Secondary Outcome Measures
Mean Change in MAS of the Primary Targeted Muscle Group.
Increased muscle tone in the primary muscle group (selected by the investigator at the first visit, based on his/her clinical judgement and in agreement with the subject, in one of the following muscle groups: elbow flexors or pronators, wrist flexors, or finger flexors) was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Least Squares (LS) mean change from baseline to each subsequent visit (including the subject's last study visit) of the MAS score is reported.
Mean Change in Fugl-Meyer Assessment for Evaluation of UL Motor Impairment.
The Fugl-Meyer assessment is a validated tool for measuring motor functioning, balance, sensation, and joint functioning in the upper or lower limbs of subjects with post-stroke hemiplegia. The assessment scale is comprised of 155 items across 5 domains: motor functioning, sensory functioning, balance, joint range of motion and joint pain. For this study, only the UL motor part was assessed using the following criteria:
A. Upper Extremity (from 0 to 36) B. Wrist (from 0 to 10) C. Hand (from 0 to 14) D. Coordination / Speed (from 0 to 6)
Total motor function scores (A-D [from 0 to 66]) were calculated and LS mean changes from baseline up to (but not including) the visit when the reinjection criteria were met were reported.
Higher values for change from baseline indicated a better outcome.
Global Assessment of Changes at Last Visit
Global assessment of changes was assessed by the investigator from Week 4 up to (but not including) the visit when the reinjection criteria were met. This endpoint was assessed by the investigator using a 5-point Likert scale to answer the following question: How does your patient feel compared to his/her condition at the first visit?
Much better
Better
No change
Worse
Much worse
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Number of Concomitant Non-drug Therapy Sessions.
The number of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). All concomitant therapies in the indication of "Post Stroke UL Spasticity" were counted by subject from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Mean Duration of Concomitant Non-drug Therapy Sessions.
The duration of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). Overall duration of concomitant therapies in the indication of "Post Stroke UL Spasticity" was computed for the period from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02321436
Brief Title
Study to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression
Acronym
ONTIME Pilot
Official Title
Asian Multicentre, Double Blind, Randomised, Placebo Controlled Pilot Study, to Assess the Impact of Dysport® Intramuscular Injections When Administered Within the First 12 Weeks After Stroke on the Time to Spasticity Progression in Adult Subjects With Upper Limb (UL) Spasticity.
Study Type
Interventional
2. Study Status
Record Verification Date
September 2022
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ipsen
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to investigate if early administration (i.e. within 12 weeks after stroke) of Dysport® 500 U injections may delay the appearance or the progression of upper limb symptomatic spasticity.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stroke, Upper Limb Spasticity
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
42 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Treatment group
Arm Type
Active Comparator
Arm Description
Dysport® 500U intramuscular injection
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Placebo intramuscular injection
Intervention Type
Biological
Intervention Name(s)
Botulinum toxin type A
Other Intervention Name(s)
AbobotulinumtoxinA (Dysport®)
Intervention Description
Subjects to receive Dysport® 500U administered intramuscularly in the targeted upper limb.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo administered intramuscularly in the targeted upper limb.
Primary Outcome Measure Information:
Title
Time Between the Initial Injection and the Appearance of Reinjection Criteria as Evaluated by the Modified Ashworth Scale (MAS) and Spasticity Symptoms
Description
The appearance of increased muscle tone was assessed using the MAS (scale ranges from 0 [no increase in muscle tone] to 4 [affected part rigid in flexion or extension]). For confirmation of reinjection criteria appearance, a subject had to have a MAS score in the primary targeted muscle group of ≥2 and at least 1 of the following 4 criteria confirming signs of symptomatic spasticity in the UL:
A Numeric Pain Rating Scale (NPRS) pain score ≥ 4 (NPRS ranges from 0 [no pain] to 10 [severe pain])
An impact on passive function measured by a score of ≥ 1 on the 4-point Likert scale (scale ranges from 0 [no impact] to 3 [severe impact])
An impact on active function measured by a score of ≥ 1 on the 4-point Likert scale
An involuntary movements score ≥1 on the 4-point Likert scale in relevant upper limb.
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Time Frame
From Week 4 up to Week 28
Secondary Outcome Measure Information:
Title
Mean Change in MAS of the Primary Targeted Muscle Group.
Description
Increased muscle tone in the primary muscle group (selected by the investigator at the first visit, based on his/her clinical judgement and in agreement with the subject, in one of the following muscle groups: elbow flexors or pronators, wrist flexors, or finger flexors) was assessed using the MAS. Scale ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). Least Squares (LS) mean change from baseline to each subsequent visit (including the subject's last study visit) of the MAS score is reported.
Time Frame
From baseline up to Week 28
Title
Mean Change in Fugl-Meyer Assessment for Evaluation of UL Motor Impairment.
Description
The Fugl-Meyer assessment is a validated tool for measuring motor functioning, balance, sensation, and joint functioning in the upper or lower limbs of subjects with post-stroke hemiplegia. The assessment scale is comprised of 155 items across 5 domains: motor functioning, sensory functioning, balance, joint range of motion and joint pain. For this study, only the UL motor part was assessed using the following criteria:
A. Upper Extremity (from 0 to 36) B. Wrist (from 0 to 10) C. Hand (from 0 to 14) D. Coordination / Speed (from 0 to 6)
Total motor function scores (A-D [from 0 to 66]) were calculated and LS mean changes from baseline up to (but not including) the visit when the reinjection criteria were met were reported.
Higher values for change from baseline indicated a better outcome.
Time Frame
From baseline up to Week 28
Title
Global Assessment of Changes at Last Visit
Description
Global assessment of changes was assessed by the investigator from Week 4 up to (but not including) the visit when the reinjection criteria were met. This endpoint was assessed by the investigator using a 5-point Likert scale to answer the following question: How does your patient feel compared to his/her condition at the first visit?
Much better
Better
No change
Worse
Much worse
Results are reported overall for subjects with both symptomatic and asymptomatic spasticity.
Time Frame
From Week 4 up to Week 28
Title
Number of Concomitant Non-drug Therapy Sessions.
Description
The number of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). All concomitant therapies in the indication of "Post Stroke UL Spasticity" were counted by subject from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Time Frame
From baseline up to Week 28
Title
Mean Duration of Concomitant Non-drug Therapy Sessions.
Description
The duration of non-drug therapy sessions that the subject received for UL spasticity in combination with injections of either Dysport® or placebo - up to and including the subject's last study visit - were recorded in the Electronic Case Report Form (eCRF) as part of concomitant medications and therapies evaluation at all study visits (Prior and Concomitant Non-Drug Therapies eCRF page). Overall duration of concomitant therapies in the indication of "Post Stroke UL Spasticity" was computed for the period from first administration of Dysport® or placebo to last study visit. Concomitant non-drug therapies were defined as received any time during study (on or after the day of the first injection of Dysport® or placebo) regardless of the start or stop date. For each subject, overlapping sessions were defined as one therapy session using the earliest start date as the start date and the latest start date as the stop date.
Time Frame
From baseline up to Week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
2 to 12 weeks after first ever stroke according to the World Health Organisation criteria (previous transient ischaemic attack or clinically silent infarct on computerised tomography (CT)/magnetic resonance imaging (MRI) are not counted as previous stroke)
Stroke confirmed by CT/MRI scan and classified as ischaemic/haemorrhagic stroke
Presence of spasticity:
either symptomatic, based on symptomatic spasticity criteria (i.e. at least one of the following items: impacted passive/active function, involuntary movements, or pain ≥4 on a numeric pain rating scale [NPRS]), in addition to increased muscle tone [Modified Ashworth Scale, MAS ≥2])
or only increased muscle tone (MAS≥2)
Exclusion Criteria:
Neuromuscular junction (NMJ) diseases, or any other neurological disorders (including prior local joint, tendon, and intrinsic muscle disorders) that could potentially interfere with assessment of spasticity in the primary targeted muscle group selected by the Investigator and in agreement with the subject
Currently receiving drugs affecting NMJ transmission e.g. aminoglycosides, aminoquinolines, cyclosporine, D penicillamine
Previous surgery of the affected muscles/ ligaments/tendons
Severe comorbidities (e.g. congestive heart failure, myocardial infarction, multiple organ failure, hepatic renal failures, severe infections)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ipsen Medical Director
Organizational Affiliation
Ipsen
Official's Role
Study Director
Facility Information:
Facility Name
Neurology Laboratory -University Malaya Medical Centre
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Center for Neurodiagnostic and Therapeutic Services Metropolitan Medical Center
City
Manila
ZIP/Postal Code
1003
Country
Philippines
Facility Name
TTSH Rehabilitation Centre Ang Mo Kio Community Hospital
City
Singapore
ZIP/Postal Code
569766
Country
Singapore
Facility Name
Department of rehabilitation Medicine Faculty of medicine Siriraj Hospital, Madihol University Hospital
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing 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.
IPD Sharing Access Criteria
Further details on Ipsen's sharing criteria, eligible studies and process for sharing are available here (https://vivli.org/members/ourmembers/).
IPD Sharing URL
https://vivli.org/members/ourmembers/
Citations:
PubMed Identifier
29933562
Citation
Rosales RL, Balcaitiene J, Berard H, Maisonobe P, Goh KJ, Kumthornthip W, Mazlan M, Latif LA, Delos Santos MMD, Chotiyarnwong C, Tanvijit P, Nuez O, Kong KH. Early AbobotulinumtoxinA (Dysport(R)) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study. Toxins (Basel). 2018 Jun 21;10(7):253. doi: 10.3390/toxins10070253.
Results Reference
derived
Learn more about this trial
Study to Assess Impact of Dysport Injections Early After Stroke on Upper Limb Spasticity Progression
We'll reach out to this number within 24 hrs