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IMPULSE - StIMulation of Brain Plasticity to Improve Upper Limb Recovery After StrokE (IMPULSE)

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ClinicalTrials.gov Identifier: NCT04124367
Recruitment Status : Recruiting
First Posted : October 11, 2019
Last Update Posted : July 1, 2021
Sponsor:
Collaborator:
VASCage GmbH
Information provided by (Responsible Party):
Ever Neuro Pharma GmbH

Tracking Information
First Submitted Date  ICMJE October 10, 2019
First Posted Date  ICMJE October 11, 2019
Last Update Posted Date July 1, 2021
Actual Study Start Date  ICMJE June 25, 2021
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 14, 2019)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 10, 2019)
Action Research Arm Test (ARAT) at day 21 [ Time Frame: Day 21 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 14, 2019)
  • Nine-Hole Peg Test (NHPT) [ Time Frame: Day 21 ]
    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.
  • Hand grip dynamometry [ Time Frame: Day 21 ]
    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.
  • National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: Day 21 ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 10, 2019)
  • 9-Hole Peg Test [ Time Frame: Day 21 ]
  • Hand grip dynamometry [ Time Frame: Day 21 ]
  • National Institutes of Health Stroke Scale (NIHSS) [ Time Frame: Day 21 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE IMPULSE - StIMulation of Brain Plasticity to Improve Upper Limb Recovery After StrokE
Official Title  ICMJE 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
Brief 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. 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Stroke
  • Subacute Stroke
Intervention  ICMJE
  • Drug: Cerebrolysin
    30 ml once daily (+70 ml 0.9% saline)
  • Device: non-invasive brain stimulation
    2 mA/35 cm² for 2x20 minutes, once daily
    Other Name: atDCS
  • Drug: Placebo
    100 ml once daily 0.9% saline
  • Device: sham intervention
    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 Arms  ICMJE
  • Active Comparator: Verum
    Interventions:
    • Drug: Cerebrolysin
    • Device: non-invasive brain stimulation
  • Placebo Comparator: Control
    Interventions:
    • Drug: Placebo
    • Device: sham intervention
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 10, 2019)
90
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date December 31, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

Disease-related:

o Study procedures:

  1. Severe sensory deficits (score of 2 on item 8 of the NIHSS)
  2. Severe aphasia (a score of ≥2 on item 9 of the NIHSS)
  3. Severe neglect (a score of 2 on item 11 of the NIHSS)
  4. 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
  5. MMSE <20
  6. Current drug or alcohol use or dependency that would interfere with adherence to study procedures
  7. Participation in another interventional study

    • Spasticity:
  8. 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
  9. 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
  10. 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:

  11. Pacemaker or brain stimulator
  12. Implanted intracranial metals in the stimulation area such as clipping, coilings, ventriculo-peritoneal shunts, endoprosthesis, cochlear implant
  13. Scalp wounds or infections in the area of stimulation
  14. 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)
  15. Breastfeeding; pregnant or trying to become pregnant
  16. 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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Edith Doppler, PhD 0043766520555 ext 411 edith.doppler@everpharma.com
Contact: Stefan Winter, PhD 0766520555 ext 422 stefan.winter@everpharma.com
Listed Location Countries  ICMJE Austria
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04124367
Other Study ID Numbers  ICMJE EVER-AT-0618
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ever Neuro Pharma GmbH
Study Sponsor  ICMJE Ever Neuro Pharma GmbH
Collaborators  ICMJE VASCage GmbH
Investigators  ICMJE
Principal Investigator: Andreas Winkler, MD, MSc Klinik Pirawarth
PRS Account Ever Neuro Pharma GmbH
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP