Controlling Coordination After Childhood Cerebellar Cancer, a Pilot Study (5C-pilot)

Controlling Coordination After Childhood Cerebellar Cancer - Pilot Study

Posterior fossa tumours (PFT) account for 2/3 of childhood brain cancers. They can be highly malignant requiring combined chemotherapy and radiotherapy post-surgery for a >50% chance of cure. PFT frequently involve the cerebellum which is responsible for coordinating movement, balance, emotional control, and links closely to control of affect and executive function. PFT survivors show highly variable profiles for cognitive and sensorimotor functioning which are influenced strongly by the severity of the pre-diagnostic or post-surgical brain injury

State-of-the-art magnetic resonance imaging (MRI) scans can allow to measure a variety of different biological processes in the brain, and the investigators believe that some of these MRI measures (called MRI biomarkers) have the potential to improve our ability to understand and monitor consequences of the ablative brain surgery and complex mechanisms of motor skills recovery. Biomarkers are very important for the development of intervention because 1) they help understand the recuperation process and 2) they allow to effectively assess whether or not a treatment or intervention works.

Transcranial magnetic stimulation (TMS) is a powerful non-invasive neuro-modulatory intervention that has the potential to evaluate the integrity of the nervous tracts from the brain to the hand. It is a procedure that applies magnetic pulses on the surface of the scalp to reach underlying brain tissue. TMS has built a reputable status among neuro-rehabilitative research, and there is currently a major effort to translate the positive research findings into clinically useful therapeutic strategies.

This study is therefore an important first step towards understanding how potential MRI biomarkers and responses to TMS relate to motor symptoms in PFT young survivors. Once completed, this study will allow the investigators to select the most promising MRI biomarkers and TMS protocols to take forward into future treatment trials. The investigators aim to stimulate the recovery of coordination skills, help the development of targeted therapies, and consequently improve long-term quality of life in children and young people with history of brain tumour.

The proposed research intends to prove the feasibility of such brain stimulation and imaging and collect some preliminary measures

Study Overview

• Status: Recruiting
• Conditions: Brain Cancer
• Intervention / Treatment: Other: Transcranial Magnetic Stimulation (TMS); Other: Magnetic Resonance Imaging (MRI); Other: Motor assessment; Other: Questionnaires

• Study Type: Observational
• Enrollment (Anticipated): 10

Contacts and Locations

• Study Contact: Name: Caroline Blanchard; Email: caroline.blanchard@nottingham.ac.uk

Study Locations

• United Kingdom
  • Nottingham, United Kingdom
    • Recruiting
    • Queen's Medical Centre
    • Contact: Madhumati Dandapani

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 22 years (ADULT, CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

4 participants with history of PFT (no history of seizure, no current cancer treatment) 6 healthy controls (no history of brain injury)

Description

Inclusion Criteria:

• Able to undergo MRI scan without sedation or general anaesthetic
• Able to give informed consent.

Exclusion Criteria:

• History of seizure
• Current cancer or post surgery treatment
• Contraindication to TMS or MRI
• Pregnancy

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Young PFT survivors	Other: Transcranial Magnetic Stimulation (TMS); With the TMS session we gather information about nerve fibres from the brain to the hand. It will last around 2 hours and 30 minutes.; Other: Magnetic Resonance Imaging (MRI); With the MRI scan we will gather information about the brain structure and function. This will last around 30 minutes.; Other: Motor assessment; The motor assessment includes a pegboard game, a "grab the alien nose" game and measure of your maximum grip force. In total it will last around 30 minutes.; Other: Questionnaires; Feasibility, tolerability of such intervention as well as quality of life of PFT survivors will be assessed thanks to questionnaires.
Age-matching controls	Other: Transcranial Magnetic Stimulation (TMS); With the TMS session we gather information about nerve fibres from the brain to the hand. It will last around 2 hours and 30 minutes.; Other: Magnetic Resonance Imaging (MRI); With the MRI scan we will gather information about the brain structure and function. This will last around 30 minutes.; Other: Motor assessment; The motor assessment includes a pegboard game, a "grab the alien nose" game and measure of your maximum grip force. In total it will last around 30 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5C-pilot Satisfaction Questionnaire	Participants rating their experience of MRI, TMS and motor assessment	6 months
Completion rate of the sessions of TMS, MRI and motor tasks	Measure of quality of MRI images (participants motion) - Feasibility will be confirmed if 50% or more of these participants complete the TMS session	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anatomical MRI metrics (PFT vs control)	Cerebellar volumetry and cerebellar parcellation - after surgery (mm3)	1 year
fMRI metrics (PFT vs control)	Functional connectivity within sensorimotor network (activation map)	1 year
Diffusion MRI metrics (PFT vs control)	Anatomical connectivity within sensorimotor network (tractography)	1 year
Single-pulse TMS metrics (PFT vs control)	Resting motor threshold (Stimulus intensity expressed as a percentage of maximal stimulator output)	1 year
Single-pulse TMS metrics (PFT vs control)	input-output curve	1 year
Single-pulse TMS metrics (PFT vs control)	Silent period (ms)	1 year
Single-pulse TMS metrics (PFT vs control)	Short-afferent inhibition	1 year
Dual-pulse TMS metrics (PFT vs control)	Intracortical & long-latency inhibition and facilitation	1 year
Dual-pulse TMS metrics (PFT vs control)	cerebellar-motor inhibition	1 year
Motor performance (PFT vs control) - Reaching and grasping task	Kinematic parameters of movement	1 year
Motor performance (PFT vs control) - Grooved pegboard	Score	1 year
Motor performance (PFT vs control) - Grip force	Maximum force (N)	1 year
Quality of life of PFT survivors: FACT-Peds-Br Questionnaire	FACT-Peds-Br Pediatric Questionnaire - For patients with Brain cancer	6 months

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Nottingham University Hospital NHS Trust; Nottingham Hospitals Charity

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 28, 2022
• Primary Completion (ANTICIPATED): July 30, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: July 23, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (ACTUAL): August 6, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 25, 2022
• Last Update Submitted That Met QC Criteria: May 18, 2022
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Transcranial Magnetic Stimulation; Motor recovery; Cerebellum; Paediatric; Posterior Fossa Tumour
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Central Nervous System Neoplasms; Nervous System Neoplasms; Cerebellar Diseases; Infratentorial Neoplasms; Brain Neoplasms; Cerebellar Neoplasms
• Other Study ID Numbers: 20047

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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