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

NCT04124367 | Terminated Phase 2

• 1 other identifier: EVER-AT-0618
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Stroke; Subacute Stroke

Outcome Measures

Primary Outcomes (1)

• 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.

  Day 21

Secondary Outcomes (3)

• Nine-Hole Peg Test (NHPT)

  Day 21

• Hand grip dynamometry

  Day 21

• National Institutes of Health Stroke Scale (NIHSS)

  Day 21

Study Arms (2)

Verum

ACTIVE COMPARATOR

Drug: Cerebrolysin; Device: non-invasive brain stimulation

Control

PLACEBO COMPARATOR

Drug: Placebo; Device: sham intervention

Interventions

Cerebrolysin DRUG

30 ml once daily (+70 ml 0.9% saline)

Verum

non-invasive brain stimulation DEVICE

2 mA/35 cm² for 2x20 minutes, once daily

Also known as: atDCS

Verum

Placebo DRUG

100 ml once daily 0.9% saline

Control

sham intervention DEVICE

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).

Control

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age, both inclusive, of all sexes
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ever Neuro Pharma GmbH: lead
• VASCage GmbH: collaborator

Study Sites (1)

Klinik Pirawarth

Bad Pirawarth, 2222, Austria

Location

MeSH Terms

Interventions

cerebrolysin

Study Officials

• Andreas Winkler, MD, MSc

  Klinik Pirawarth

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2019
• First Posted: October 11, 2019
• Study Start: June 25, 2021
• Primary Completion: March 21, 2022
• Study Completion: March 21, 2022
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)