Chronic StrokePhase 2IMPULSENCT04124367
IMPULSE - StIMulation of Brain Plasticity to Improve Upper Limb Recovery After StrokE
A Phase 2 study testing Cerebrolysin and non-invasive brain stimulation in people with Chronic Stroke and Subacute Stroke, run by Ever Neuro Pharma GmbH at 1 site in Austria.
Trial summary
Stroke is a leading cause of adult long-term disability worldwide. Recovery of arm and hand function after stroke is limited to about 50% of patients and full recovery is achieved in only 12% of stroke survivors by 6 months after stroke. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Chronic Stroke, Subacute Stroke
- What is being tested?
- Cerebrolysin and non-invasive brain stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 1 siteAustria
- Study dates
- 25 Jun 2021to 21 Mar 2022
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18-80 years of age, both inclusive, of all sexes
- 8 weeks to 12 months after a first-ever hemispheric subcortical ischemic stroke, confirmed by imaging
- Pre-stroke modified Rankin Scale (mRS) 0 or 1
- Action Research Arm Test (ARAT) score 13-50, both inclusive
- Shoulder Abduction Finger Extension (SAFE) score ≥5
- Patient participates voluntarily and gave written informed consent
Who cannot join
- Disease-related:
- o Study procedures:
- Severe sensory deficits (score of 2 on item 8 of the NIHSS)
- Severe aphasia (a score of ≥2 on item 9 of the NIHSS)
- Severe neglect (a score of 2 on item 11 of the NIHSS)
- Co-morbid conditions such as fractures, osteoarthritis, fixed or severely interfering contraction or deformity in the affected limb, polyneuropathy and/or ischemic peripheral disease if the sensorimotor functions of the upper extremities are affected, other neurological disease(s) or known brain abnormalities, acute coronary syndrome, severe heart disease (NYHA class III or IV), cancer, severe liver disease (hepatic disease associated with coagulopathy [prothrombin time prolonged beyond the normal range] and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C), and other major medical conditions that, in the opinion of the site investigator, might influence efficacy or safety assessment
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- MMSE <20
- Current drug or alcohol use or dependency that would interfere with adherence to study procedures
- Participation in another interventional study
- Spasticity:
- Major spasticity as indicated by the Modified Ashworth Spasticity Scale >2/4 in either elbow flexors, wrist flexors or finger flexors of the affected limb
- Injection of botulinum toxin to the affected upper limb in the last three months, or the need of an injection of botulinum toxin anytime during the study period
- Injection of phenol to the affected upper limb in the last six months, or the need of an injection of phenol anytime during the study period
- Exposure-related:
- Pacemaker or brain stimulator
- Implanted intracranial metals in the stimulation area such as clipping, coilings, ventriculo-peritoneal shunts, endoprosthesis, cochlear implant
- Scalp wounds or infections in the area of stimulation
- Any condition that would represent a contraindication for Cerebrolysin administration:
- hypersensitivity to one of the components of the drug
- epilepsy
- severe renal impairment (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2 as assessed at local laboratory within one month before screening)
- Breastfeeding; pregnant or trying to become pregnant
- Concomitant medications
- with potential negative effects on cortical excitability or plasticity (e.g. psycholeptics (ATC class N05), antiepileptics, neuroleptics, benzodiazepines, dextromethorphan)
- with potential positive effects on cortical excitability or plasticity (e.g. SSRIs, SNRIs, dopaminergic preparations, memantine, AChEIs, amphetamines) - except if the patient is on a stable dose for a minimum of four weeks. Special attention should be given to possible additive effects when Cerebrolysin is used in conjunction with antidepressants/MAO inhibitors. High doses of MAO inhibitors in combination with higher dosages of Cerebrolysin (30-40 ml) have been reported to increase blood pressure.
- with neuroprotective/neurotrophic/nootropic effects (e.g. ginkgo biloba, erythropoietin, citicoline, amantadine, piracetam)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: IMPULSE StIMulation of Brain Plasticity to Improve Upper Limb Recovery After StrokE A Prospective, Multi-center, Randomized, Double-blind Study to Assess Efficacy and Safety of Neuroplastic Intervention by Cerebrolysin and atDCS on Motor Function Recovery in Subacute and Chronic Stroke Patients
Stroke is a leading cause of adult long-term disability worldwide. Recovery of arm and hand function after stroke is limited to about 50% of patients and full recovery is achieved in only 12% of stroke survivors by 6 months after stroke. Within the first 8-12 weeks post-stroke, a proportional recovery of 70%, corresponding to good recovery, may be achieved, but at later stages no major gain is observed with current therapy practices. Accordingly, there is a need to find new potential therapeutic tools to enhance post-stroke motor recovery. Rehabilitation supported by neuroplastic intervention is a new and pragmatic therapeutic approach in the treatment of stroke, giving way to a concept of 'recovery enhancers'.
The objective of this study is to assess whether an additional therapy with Cerebrolysin and anodal transcranial direct current stimulation (atDCS) increases the success of conventional rehabilitation therapy in subacute and chronic stroke patients with unexploited potential for functional recovery despite intact structural and functional pathways in the brain.
Read more
Hypothesis:
The hypothesis is that the combination of Cerebrolysin and atDCS facilitates motor learning in subacute and chronic stroke patients. Accordingly, motor function recovery at day 21 post-baseline is expected to be higher in the verum group (conventional rehabilitation + task-specific motor training + Cerebrolysin + atDCS) as compared to the control group (conventional rehabilitation + task-specific motor training + placebo + sham-transcranial direct current stimulation).
The primary objective is to show a significantly higher proportional recovery rate in the Action Research Arm Test (ARAT) at day 21 post-baseline in the verum group as compared to the control group.
The secondary objective is to assess the impact of this neuroplastic intervention on finger dexterity (Nine-hole peg test - 9HPT), hand grip strength, and neurological deficits (National Institutes of Healths Stroke Scale - NIHSS) at the end of therapy (day 21 post-baseline). Safety data are collected throughout the study and thereafter in case of ongoing serious adverse events (SAEs) at study endpoint.
Optional secondary parameters include electroencephalography (EEG) parameters and Brain Derived Neurotrophic Factor (BDNF) status analyses to document plastic changes in the brain, in particular changes of the cortical network functionality during neurorehabilitation, and to assess the impact of neuroplastic intervention on the BDNF synthesis rate as well as the influence of different BDNF polymorphisms.
- Conditions
- Chronic Stroke, Subacute Stroke
- Being tested
- Cerebrolysin, non-invasive brain stimulation, Placebo, sham intervention
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CerebrolysinDrug
30 ml once daily (+70 ml 0.9% saline)
non-invasive brain stimulationDevice
Also called atDCS
2 mA/35 cm² for 2x20 minutes, once daily
PlaceboDrug
100 ml once daily 0.9% saline
sham interventionDevice
0 mA/35 cm² for 2x20 minutes, once daily Run-in phase consisting of ramp-up (10 seconds), stimulation (10 seconds), and ramp-down (10 seconds).
| Study group | Role | What they receive |
|---|---|---|
| Verum | Active comparator | Not described Receives: Drug: Cerebrolysin; Device: non-invasive brain stimulation |
| Control | Placebo comparator | Not described Receives: Drug: Placebo; Device: sham intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Action Research Arm Test (ARAT)
The ARAT assesses upper limb functioning. The ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement. The total score on the ARAT ranges from 0 to 57, with the lowest score indicating that no movements can be performed, and the upper score indicating normal performance.
Measured: Day 21
Secondary outcomes (3)
Nine-Hole Peg Test (NHPT)
The NHPT is used to measure finger dexterity. The NHPT is composed of a square board with 9 pegs. At one end of the board are holes for the pegs to fit in to, and at the other end is a shallow round dish to store the pegs. The NHPT is administered by asking the patient to take the pegs from a container, one by one, and placing them into the holes on the board, as quickly as possible. Patients must then remove the pegs from the holes, one by one, and replace them back into the container. Patients are scored based on the time taken to complete the test activity, recorded in seconds.
Measured: Day 21
Hand grip dynamometry
Hand grip dynamometry measures grip strength. The best out of three strength tests of the impaired hand is used as resultant score. A score is taken with the non-affected hand, followed by the impaired hand.
Measured: Day 21
National Institutes of Health Stroke Scale (NIHSS)
The NIHSS is a 15-item impairment scale, intended to evaluate neurologic outcome and degree of recovery for patients with stroke. Total scores on the NIHSS range from 0 - 42, with higher values reflecting more severe cerebral infarcts and correspondingly more severe neurological impairment.
Measured: Day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2019
- Study start25 Jun 2021
- Primary completion21 Mar 2022
- Study completion21 Mar 2022
Why it stopped: for strategic and pandemic reasons
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ever Neuro Pharma GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- VASCage GmbH
- Responsible party
- Sponsor
- Investigators
- Andreas Winkler, MD, MSc, Principal investigator, Klinik Pirawarth
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04124367
- Sponsor's protocol ID
- EVER-AT-0618
- Acronym
- IMPULSE
- Status last verified
- Jul 2022
- First submitted
- 10 Oct 2019
- Last updated
- 28 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IMPULSE StIMulation of Brain Plasticity to Improve Upper Limb Recovery After StrokE A Prospective, Multi-center, Randomized, Double-blind Study to Assess Efficacy and Safety of Neuroplastic Intervention by Cerebrolysin and atDCS on Motor Function Recovery in Subacute and Chronic Stroke Patients
- ClinicalTrials.gov ID
- NCT04124367
- Acronym / sponsor ID
- IMPULSE / EVER-AT-0618
- Conditions
- Chronic Stroke, Subacute Stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: for strategic and pandemic reasons
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Ever Neuro Pharma GmbHIndustry (pharma, biotech, devices)
- Collaborators
- VASCage GmbH
- Study start
- 25 Jun 2021 (actual)
- Primary completion
- 21 Mar 2022 (actual)
- Study completion
- 21 Mar 2022 (actual)
- First posted
- 11 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stroke is a leading cause of adult long-term disability worldwide. Recovery of arm and hand function after stroke is limited to about 50% of patients and full recovery is achieved in only 12% of stroke survivors by 6 months after stroke. Within the first 8-12 weeks post-stroke, a proportional recovery of 70%, corresponding to good recovery, may be achieved, but at later stages no major gain is observed with current therapy practices. Accordingly, there is a need to find new potential therapeutic tools to enhance post-stroke motor recovery. Rehabilitation supported by neuroplastic intervention is a new and pragmatic therapeutic approach in the treatment of stroke, giving way to a concept of 'recovery enhancers'.
The objective of this study is to assess whether an additional therapy with Cerebrolysin and anodal transcranial direct current stimulation (atDCS) increases the success of conventional rehabilitation therapy in subacute and chronic stroke patients with unexploited potential for functional recovery despite intact structural and functional pathways in the brain.
Hypothesis:
The hypothesis is that the combination of Cerebrolysin and atDCS facilitates motor learning in subacute and chronic stroke patients. Accordingly, motor function recovery at day 21 post-baseline is expected to be higher in the verum group (conventional rehabilitation + task-specific motor training + Cerebrolysin + atDCS) as compared to the control group (conventional rehabilitation + task-specific motor training + placebo + sham-transcranial direct current stimulation).
The primary objective is to show a significantly higher proportional recovery rate in the Action Research Arm Test (ARAT) at day 21 post-baseline in the verum group as compared to the control group.
The secondary objective is to assess the impact of this neuroplastic intervention on finger dexterity (Nine-hole peg test - 9HPT), hand grip strength, and neurological deficits (National Institutes of Healths Stroke Scale - NIHSS) at the end of therapy (day 21 post-baseline). Safety data are collected throughout the study and thereafter in case of ongoing serious adverse events (SAEs) at study endpoint.
Optional secondary parameters include electroencephalography (EEG) parameters and Brain Derived Neurotrophic Factor (BDNF) status analyses to document plastic changes in the brain, in particular changes of the cortical network functionality during neurorehabilitation, and to assess the impact of neuroplastic intervention on the BDNF synthesis rate as well as the influence of different BDNF polymorphisms.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Verum | Active comparator | Drug: Cerebrolysin, Device: non-invasive brain stimulation |
| Control | Placebo comparator | Drug: Placebo, Device: sham intervention |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 18-80 years of age, both inclusive, of all sexes
- 8 weeks to 12 months after a first-ever hemispheric subcortical ischemic stroke, confirmed by imaging
- Pre-stroke modified Rankin Scale (mRS) 0 or 1
- Action Research Arm Test (ARAT) score 13-50, both inclusive
- Shoulder Abduction Finger Extension (SAFE) score ≥5
Key exclusion criteria (26 listed)
- Severe sensory deficits (score of 2 on item 8 of the NIHSS)
- Severe aphasia (a score of ≥2 on item 9 of the NIHSS)
- Severe neglect (a score of 2 on item 11 of the NIHSS)
- Co-morbid conditions such as fractures, osteoarthritis, fixed or severely interfering contraction or deformity in the affected limb, polyneuropathy and/or ischemic peripheral disease if the sensorimotor functions of the upper extremities are affected, other neurological disease(s) or known brain abnormalities, acute coronary syndrome, severe heart disease (NYHA class III or IV), cancer, severe liver disease (hepatic disease associated with coagulopathy [prothrombin time prolonged beyond the normal range] and clinically relevant bleeding risk including cirrhotic patients with Child Pugh B and C), and other major medical conditions that, in the opinion of the site investigator, might influence efficacy or safety assessment
- MMSE <20
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cerebrolysin30 ml once daily (+70 ml 0.9% saline) | Drug | Verum |
| non-invasive brain stimulationAlso: atDCS2 mA/35 cm² for 2x20 minutes, once daily | Device | Verum |
| Placebo100 ml once daily 0.9% saline | Drug | Control |
| sham intervention0 mA/35 cm² for 2x20 minutes, once daily Run-in phase consisting of ramp-up (10 seconds), stimulation (10 seconds), and ramp-down (10 seconds). | Device | Control |
Primary outcome
Action Research Arm Test (ARAT)
Time frame: Day 21
The ARAT assesses upper limb functioning. The ARAT consists of 19 items grouped into four subscales: grasp, grip, pinch, and gross movement. The total score on the ARAT ranges from 0 to 57, with the lowest score indicating that no movements can be performed, and the upper score indicating normal performance.
3 secondary outcomes
Nine-Hole Peg Test (NHPT)
Time frame: Day 21
Hand grip dynamometry
Time frame: Day 21
National Institutes of Health Stroke Scale (NIHSS)
Time frame: Day 21
Results and safety
The study was stopped early (reason given: for strategic and pandemic reasons). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Winkler, MD, MSc principal investigator
Klinik Pirawarth
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cerebrolysin and non-invasive brain stimulation in people with Chronic Stroke and Subacute Stroke, run by Ever Neuro Pharma GmbH at 1 site in Austria.
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 6 inclusion and 26 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 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: for strategic and pandemic reasons). Results are not available in the source record.
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?
Action Research Arm Test (ARAT) (time frame: Day 21). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Jul 2022.