NCT05005780

Brief Summary

This randomized, controlled, double-blind clinical pilot trial investigates the therapeutic potential of a novel personalized therapeutic brain-stimulation protocol in chronic stroke patients with spasticity. Stroke patients will either receive ipsilesional 100 Hz transcranial magnetic stimulation (TMS) triplet burst protocol synchronized to the ongoing µ-alpha oscillation or contralesional 1 Hz repetitive TMS (rTMS) protocol. Motor recovery is assessed directly after as well as three months after completion of the therapy.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for not_applicable stroke

Timeline
Completed

Started Oct 2019

Typical duration for not_applicable stroke

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 2, 2019

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

July 21, 2021

Completed
26 days until next milestone

First Posted

Study publicly available on registry

August 16, 2021

Completed
1 year until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2022

Completed
Last Updated

August 18, 2023

Status Verified

July 1, 2021

Enrollment Period

2.9 years

First QC Date

July 21, 2021

Last Update Submit

August 16, 2023

Conditions

Stroke

Outcome Measures

Primary Outcomes (2)

  • Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)

    Upper limb, affected side

    Difference of score directly before intervention and score directly after intervention

  • Change in Fugl-Meyer Assessment Upper Extremity (FMA-UE)

    Upper limb, affected side

    Difference of score directly before intervention and score 3 months after intervention

Secondary Outcomes (4)

  • Change in Wolf-Motor Function Test

    Difference of score directly before intervention and score directly after intervention

  • Change in Modified Ashworth Scale

    Difference of score directly before intervention and score directly after intervention

  • Change in PSAD spasticity assessment device score

    Difference of score directly before intervention and score directly after intervention

  • Change in Resting-motor-threshold (RMT)

    Difference of score directly before intervention and score directly after intervention

Study Arms (2)

µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts

EXPERIMENTAL

µ-rhythm (The µ rhythm frequency band is defined by activity falling between 8 and 13 Hz and recorded by scalp electrodes over the sensorimotor cortex during waking neural activity) negative peak triggered TMS of ipsilesional primary motor cortex, consisting of 400 triple pulses at 100 Hz, delivered at a mean inter-triple pulse interval of 3.0 s. Stimulation intensity: 100% resting motor threshold.

Device: Negative peak triggered 100 Hz triplet burst TMS

contralesional 1 Hz rTMS

ACTIVE COMPARATOR

1200 stimuli to the contralesional primary motor cortex at 1 Hz. Stimulation intensity: 115% resting motor threshold.

Device: 1 Hz rTMS

Interventions

Negative peak triggered 100 Hz triplet burst TMSDEVICE

MagVenture MagPro X100: Ipsilesional negative peak triggered 100 Hz triplet burst TMS.

µ-alpha oscillation coupled ipsilesional 100 Hz triplet bursts
1 Hz rTMSDEVICE

MagVenture MagPro X100: Contralesional 1 Hz rTMS.

contralesional 1 Hz rTMS

Eligibility Criteria

Age18 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients are between 18 to 85 years old
  • Patient suffers from chronic stroke including hand/arm paresis and spasticity
  • Ipsilesional motor evoked potentials (MEPs) can be evoked (EMG \> 50uV)
  • RMT of contralesional side \< 70% maximum stimulator output (MSO)
  • Patient is willing to comply with the study restrictions.
  • Subject FMA-UE at the lesioned side is \<= 60.

You may not qualify if:

  • Patient is under the age of legal consent.
  • Patient has a history of seizure disorder.
  • Patient with intake of pro-convulsive medication, e.g. , chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, MDMA (ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma-hydroxybutyrate (GHB), alcohol, theophylline, in accord with present consensus guidelines on safety, ethical considerations, and application of TMS in clinical practice and research (Rossi et al., 2009, 2021).
  • Subject with intake of muscle-relaxing medication (e.g. baclofen, tizanidine, gabapentin,tolperisone, THC and derivates)
  • When spasticity is treated with botox there have to be at least tree months since the last injection
  • Patient has a cardiac pacemaker, implanted medication pump, intracardiac line, that is located close to (≤ 10 cm) to the location of activation of the TMS coil or acute, unstable cardiac disease.
  • Patient has an intracranial implant (e.g., aneurysm clips, shunts, stimula-tors, cochlear implants, or electrodes) or any other metal object that is located close to (≤ 10 cm) to the location of activation of the TMS coil (excluding the mouth) and that cannot be safely removed.
  • Patient has participated in another study within 2 weeks prior to the first study visit.
  • Patient is pregnant or trying to get pregnant.
  • Patient is unable to give informed consent.
  • Patient is unable to understand the instructions of the FMA-UE or not motivated to follow these instructions.
  • Patients who have contractions and therefore can't move.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Tübingen, Department for Neurology and Stroke

Tübingen, Baden-Wurttemberg, 72076, Germany

Location

Related Publications (1)

  • Mahmoud W, Baur D, Zrenner B, Brancaccio A, Belardinelli P, Ramos-Murguialday A, Zrenner C, Ziemann U. Brain state-dependent repetitive transcranial magnetic stimulation for motor stroke rehabilitation: a proof of concept randomized controlled trial. Front Neurol. 2024 Aug 26;15:1427198. doi: 10.3389/fneur.2024.1427198. eCollection 2024.

    PMID: 39253360DERIVED

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Ulf Ziemann, Prof. Dr.

    University Hospital Tübingen, Department of Neurology and Stroke

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 21, 2021

First Posted

August 16, 2021

Study Start

October 2, 2019

Primary Completion

August 31, 2022

Study Completion

August 31, 2022

Last Updated

August 18, 2023

Record last verified: 2021-07

Locations

DE(1)