Priming Effects of Ultra-high Frequency Quattro Pulse Transcranial Brain Stimulation Prior to Hand Motor Function Training in Children With Unilateral Spastic Cerebral Palsy (TRAINCP)

Unilateral spastic cerebral palsy (USCP) leads to life-long impairment with a hemiparesis of the affected side of the body. Rehabilitation efforts combine evidence based methods such as constrained induced movement therapy (CIMT) or hand-arm bimanual intensive therapy (HABIT) as well as training in daily life activities and psychological support in order to improve participation. It has been tried to enhance hand motor function trainings with non-invasive brain stimulation. However, evidence of this promising approach is limited. This might be due to a non-consideration of the individually different types of cortico-spinal projections to the paretic hand that demonstrated to be of highly relevant for the therapy of these children. Approximately one third of such patients control their paretic hands via crossed projections from the affected hemisphere (CONTRA), while one third uses ipsilateral projections from the contralesional hemisphere (IPSI). This study aims - for the first time - to enhance the effects of the training by priming the primary motor cortex (M1) of the paretic hand with a newly established high frequency quadri-pulse theta burst stimulation (qTBS) in a randomized, patient and evaluator blind, sham-controlled approach, for the first time taking the individual type of cortico-spinal reorganization (CONTRA vs IPSI) into account. This promising and neurophysiologically motivated approach is likely to ameliorate hand function in children with USCP.

Study Overview

• Status: Recruiting
• Conditions: Cerebral Palsy, Spastic; Transcranial Magnetic Stimulation, Repetitive
• Intervention / Treatment: Other: Quadri-pulse theta burst stimulation

• Study Type: Interventional
• Enrollment (Estimated): 32
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Volker Mall, Prof.; Phone Number: +49 (0)89 71009-233; Email: volker.mall@kbo.de
• Study Contact Backup: Name: Nikolai Jung, PD Dr. med; Phone Number: +49 (0)89 71009-236; Email: nikolai.jung@tum.de

Study Locations

• Germany
  • Munich, Germany, 81377
    • Recruiting
    • Technical University Munich
    • Contact: Volker Mall, Prof.; Phone Number: +49 (0)89 71009-233; Email: volker.mall@kbo.de
    • Contact: Nikolai Jung, Dr.; Phone Number: +49 (0)89 71009-236; Email: nikolai.jung@tum.de
  • Vogtareuth, Germany, 83569
    • Recruiting
    • Clinic for Neuropediatrics and Neurorehabilitation, Epilepsy Center for Children and Adolescents, Schön Klinik
    • Contact: Steffen Berweck, Prof.; Phone Number: +49 (0)8038 901418; Email: sberweck@schoen-kliniken.de
    • Contact: Julia Hartmann; Phone Number: +49 (0)8038 901418; Email: JHartmann@schoen-klinik.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Assured diagnosis of USCP.
2. Children aged 6 to 18 years with USCP
3. Dated and signed informed consent of legal guardian, informed assent from minor

Exclusion Criteria:

1. Therapy refractory epilepsy
2. Seizures within the last 2 years
3. More than 1 anti epileptic drugs
4. Implanted shunt system
5. If singular primary motor cortex cannot be identified by TMS, e.g. because of bilateral cortico-spinal reorganization or resting motor threshold above 80% maximum stimulator output (MSO)
6. Severe mental retardation
7. Psychiatric diseases
8. Pregnancy
9. Uncooperative patients

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Real transcranial magnetic stimulation applied	Other: Quadri-pulse theta burst stimulation; High frequency transcranial quadri-pulse theta burst stimulation prior to hand motor function training
Sham Comparator: Sahm-control; Sham transcranial magnetic stimulation applied	Other: Quadri-pulse theta burst stimulation; High frequency transcranial quadri-pulse theta burst stimulation prior to hand motor function training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assisting hand assessment	Difference in change of logit assisting hand assessment scores between the TMS and sham-TMS group from baseline to end of 10 days intensive hand function training.	10 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Corticospinal reorganization	Subgroup analyses of the primary endpoint (cortico-spinal organization, age and sex) will be computed.	1 year
Assisting hand assessement - smallest detectable difference	Number of patients per treatment group who achieved the smallest detectable difference in logit assisting hand assessment score of 5 points at visit 12.	1 year
Assisting hand assessement - Follow up	Difference in the assisting hand assessment logit score between the TMS and sham-TMS group 12 months after the standardized hand motor function training.	1 year
Neuronal plasticity	Differences in neuronal plasticity as measured by motor evoked potentials with suprathreshold TMS single pulses between baseline and visit 12 as well as after 12 months follow-up.	1 year
Box-and-blocks test	Differences of Blocks transferred with the Box-and-blocks test between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up	1 year
Goal attainment scaling	Differences in Goal Attainment Scaling between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up.	1 year
Canadian occupational performance measure	Differences in the Canadian Occupational Performance Measure scale between the TMS and sham-TMS group between baseline and visit 12 as well as after 12 months follow-up.	1 year

Collaborators and Investigators

• Sponsor: Technical University of Munich
• Collaborators: German Federal Ministry of Education and Research

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): October 31, 2025
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: December 7, 2021
• First Submitted That Met QC Criteria: December 7, 2021
• First Posted (Actual): December 21, 2021

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 22, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Unilateral Spastic Cerebral Palsy; Cortico-spinal Reorganization; Sham-controlled Trial; Intensive Hand Function Training
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Damage, Chronic; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Manifestations; Muscle Hypertonia; Cerebral Palsy; Paralysis; Muscle Spasticity
• Other Study ID Numbers: TRA-MAL-0034-I

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Sharing upon request planned
• IPD Sharing Access Criteria: The study protocol will be published in an international journal. Data will be available for other reseachers upon request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No