<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04501731</url>
  </required_header>
  <id_info>
    <org_study_id>20047</org_study_id>
    <nct_id>NCT04501731</nct_id>
  </id_info>
  <brief_title>Controlling Coordination After Childhood Cerebellar Cancer, a Pilot Study</brief_title>
  <acronym>5C-pilot</acronym>
  <official_title>Controlling Coordination After Childhood Cerebellar Cancer - Pilot Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nottingham University Hospital NHS Trust</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nottingham Hospitals Charity</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Posterior fossa tumours (PFT) account for 2/3 of childhood brain cancers. They can be highly&#xD;
      malignant requiring combined chemotherapy and radiotherapy post-surgery for a &gt;50% chance of&#xD;
      cure. PFT frequently involve the cerebellum which is responsible for coordinating movement,&#xD;
      balance, emotional control, and links closely to control of affect and executive function.&#xD;
      PFT survivors show highly variable profiles for cognitive and sensorimotor functioning which&#xD;
      are influenced strongly by the severity of the pre-diagnostic or post-surgical brain injury&#xD;
&#xD;
      State-of-the-art magnetic resonance imaging (MRI) scans can allow to measure a variety of&#xD;
      different biological processes in the brain, and the investigators believe that some of these&#xD;
      MRI measures (called MRI biomarkers) have the potential to improve our ability to understand&#xD;
      and monitor consequences of the ablative brain surgery and complex mechanisms of motor skills&#xD;
      recovery. Biomarkers are very important for the development of intervention because 1) they&#xD;
      help understand the recuperation process and 2) they allow to effectively assess whether or&#xD;
      not a treatment or intervention works.&#xD;
&#xD;
      Transcranial magnetic stimulation (TMS) is a powerful non-invasive neuro-modulatory&#xD;
      intervention that has the potential to evaluate the integrity of the nervous tracts from the&#xD;
      brain to the hand. It is a procedure that applies magnetic pulses on the surface of the scalp&#xD;
      to reach underlying brain tissue. TMS has built a reputable status among neuro-rehabilitative&#xD;
      research, and there is currently a major effort to translate the positive research findings&#xD;
      into clinically useful therapeutic strategies.&#xD;
&#xD;
      This study is therefore an important first step towards understanding how potential MRI&#xD;
      biomarkers and responses to TMS relate to motor symptoms in PFT young survivors. Once&#xD;
      completed, this study will allow the investigators to select the most promising MRI&#xD;
      biomarkers and TMS protocols to take forward into future treatment trials. The investigators&#xD;
      aim to stimulate the recovery of coordination skills, help the development of targeted&#xD;
      therapies, and consequently improve long-term quality of life in children and young people&#xD;
      with history of brain tumour.&#xD;
&#xD;
      The proposed research intends to prove the feasibility of such brain stimulation and imaging&#xD;
      and collect some preliminary measures&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 28, 2022</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">July 30, 2022</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <target_duration>1 Day</target_duration>
  <primary_outcome>
    <measure>5C-pilot Satisfaction Questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>Participants rating their experience of MRI, TMS and motor assessment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Completion rate of the sessions of TMS, MRI and motor tasks</measure>
    <time_frame>6 months</time_frame>
    <description>Measure of quality of MRI images (participants motion) - Feasibility will be confirmed if 50% or more of these participants complete the TMS session</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Anatomical MRI metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Cerebellar volumetry and cerebellar parcellation - after surgery (mm3)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fMRI metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Functional connectivity within sensorimotor network (activation map)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diffusion MRI metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Anatomical connectivity within sensorimotor network (tractography)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Resting motor threshold (Stimulus intensity expressed as a percentage of maximal stimulator output)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>input-output curve</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Silent period (ms)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Single-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Short-afferent inhibition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dual-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>Intracortical &amp; long-latency inhibition and facilitation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dual-pulse TMS metrics (PFT vs control)</measure>
    <time_frame>1 year</time_frame>
    <description>cerebellar-motor inhibition</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motor performance (PFT vs control) - Reaching and grasping task</measure>
    <time_frame>1 year</time_frame>
    <description>Kinematic parameters of movement</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motor performance (PFT vs control) - Grooved pegboard</measure>
    <time_frame>1 year</time_frame>
    <description>Score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Motor performance (PFT vs control) - Grip force</measure>
    <time_frame>1 year</time_frame>
    <description>Maximum force (N)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life of PFT survivors: FACT-Peds-Br Questionnaire</measure>
    <time_frame>6 months</time_frame>
    <description>FACT-Peds-Br Pediatric Questionnaire - For patients with Brain cancer</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Brain Cancer</condition>
  <arm_group>
    <arm_group_label>Young PFT survivors</arm_group_label>
  </arm_group>
  <arm_group>
    <arm_group_label>Age-matching controls</arm_group_label>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Transcranial Magnetic Stimulation (TMS)</intervention_name>
    <description>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.</description>
    <arm_group_label>Age-matching controls</arm_group_label>
    <arm_group_label>Young PFT survivors</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Magnetic Resonance Imaging (MRI)</intervention_name>
    <description>With the MRI scan we will gather information about the brain structure and function. This will last around 30 minutes.</description>
    <arm_group_label>Age-matching controls</arm_group_label>
    <arm_group_label>Young PFT survivors</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Motor assessment</intervention_name>
    <description>The motor assessment includes a pegboard game, a &quot;grab the alien nose&quot; game and measure of your maximum grip force. In total it will last around 30 minutes.</description>
    <arm_group_label>Age-matching controls</arm_group_label>
    <arm_group_label>Young PFT survivors</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Questionnaires</intervention_name>
    <description>Feasibility, tolerability of such intervention as well as quality of life of PFT survivors will be assessed thanks to questionnaires.</description>
    <arm_group_label>Young PFT survivors</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        4 participants with history of PFT (no history of seizure, no current cancer treatment) 6&#xD;
        healthy controls (no history of brain injury)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Able to undergo MRI scan without sedation or general anaesthetic&#xD;
&#xD;
          -  Able to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of seizure&#xD;
&#xD;
          -  Current cancer or post surgery treatment&#xD;
&#xD;
          -  Contraindication to TMS or MRI&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>22 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Caroline Blanchard</last_name>
    <email>caroline.blanchard@nottingham.ac.uk</email>
  </overall_contact>
  <location>
    <facility>
      <name>Queen's Medical Centre</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Madhumati Dandapani</last_name>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 23, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>May 18, 2022</last_update_submitted>
  <last_update_submitted_qc>May 18, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Motor recovery</keyword>
  <keyword>Transcranial Magnetic Stimulation</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Paediatric</keyword>
  <keyword>Cerebellum</keyword>
  <keyword>Posterior Fossa Tumour</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Neoplasms</mesh_term>
    <mesh_term>Cerebellar Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04501731
org study id: 20047
nct id: NCT04501731
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
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
observational model: Case-Control
time perspective: Cross-Sectional
measure: 5C-pilot Satisfaction Questionnaire
time frame: 6 months
description: Participants rating their experience of MRI, TMS and motor assessment
measure: Completion rate of the sessions of TMS, MRI and motor tasks
time frame: 6 months
description: Measure of quality of MRI images (participants motion) - Feasibility will be confirmed if 50% or more of these participants complete the TMS session
measure: Anatomical MRI metrics (PFT vs control)
time frame: 1 year
description: Cerebellar volumetry and cerebellar parcellation - after surgery (mm3)
measure: fMRI metrics (PFT vs control)
time frame: 1 year
description: Functional connectivity within sensorimotor network (activation map)
measure: Diffusion MRI metrics (PFT vs control)
time frame: 1 year
description: Anatomical connectivity within sensorimotor network (tractography)
measure: Single-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: Resting motor threshold (Stimulus intensity expressed as a percentage of maximal stimulator output)
measure: Single-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: input-output curve
measure: Single-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: Silent period (ms)
measure: Single-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: Short-afferent inhibition
measure: Dual-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: Intracortical & long-latency inhibition and facilitation
measure: Dual-pulse TMS metrics (PFT vs control)
time frame: 1 year
description: cerebellar-motor inhibition
measure: Motor performance (PFT vs control) - Reaching and grasping task
time frame: 1 year
description: Kinematic parameters of movement
measure: Motor performance (PFT vs control) - Grooved pegboard
time frame: 1 year
description: Score
measure: Motor performance (PFT vs control) - Grip force
time frame: 1 year
description: Maximum force (N)
measure: Quality of life of PFT survivors: FACT-Peds-Br Questionnaire
time frame: 6 months
description: FACT-Peds-Br Pediatric Questionnaire - For patients with Brain cancer
arm group label: Young PFT survivors
arm group label: Age-matching controls
intervention type: Other
intervention name: Transcranial Magnetic Stimulation (TMS)
description: 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.
arm group label: Age-matching controls
arm group label: Young PFT survivors
intervention type: Other
intervention name: Magnetic Resonance Imaging (MRI)
description: With the MRI scan we will gather information about the brain structure and function. This will last around 30 minutes.
arm group label: Age-matching controls
arm group label: Young PFT survivors
intervention type: Other
intervention name: Motor assessment
description: 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.
arm group label: Age-matching controls
arm group label: Young PFT survivors
intervention type: Other
intervention name: Questionnaires
description: Feasibility, tolerability of such intervention as well as quality of life of PFT survivors will be assessed thanks to questionnaires.
arm group label: Young PFT survivors
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 16 Years
maximum age: 22 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Caroline Blanchard
email: caroline.blanchard@nottingham.ac.uk
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Brain Neoplasms
mesh term: Cerebellar Neoplasms
sharing ipd: Undecided