xml: <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/NCT05989646</url>
    </required_header>
    <id_info>
      <org_study_id>N-20210004</org_study_id>
      <nct_id>NCT05989646</nct_id>
    </id_info>
    <brief_title>Brain Activity Among Children With Overactive Bladder and Daytime Urinary Incontinence and Healthy Children</brief_title>
    <official_title>Brain Activity Among Children With Overactive Bladder and Daytime Urinary Incontinence and Healthy Children, and Modulation of Brain Activity by Transcutaneous Electrical Nerve Stimulation - a Functional Magnetic Resonance Imaging Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Aalborg University Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Aarhus University Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Regional Hospital West Jutland</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>North Denmark Regional Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Aalborg University Hospital</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The aim of this study is to investigate whether the activity in brain areas controlling the&#xD;
        bladder is different among children suffering from Overactive Bladder (OAB) and Daytime&#xD;
        Urinary Incontinence (DUI) compared to age- and gender-matched healthy children without&#xD;
        bladder symptoms. Moreover, the aim is to investigate if sacral transcutaneous electric nerve&#xD;
        stimulation (TENS) has a central mechanism of action. Children with OAB and DUI will be&#xD;
        recruited from involved pediatric departments, and functional magnetic resonance imaging&#xD;
        (fMRI) will be performed before and after 10 weeks of sacral TENS. In healthy children&#xD;
        without bladder symptoms, only the baseline fMRI will be performed.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Daytime Urinary Incontinence (DUI) is a common condition among children affecting 2.1-21.8 %&#xD;
        of children aged 4.5-17 years. DUI is most often caused by a functional overactive bladder&#xD;
        (OAB) leading to urgent desire to void (urgency) and frequent urinations (frequency). In some&#xD;
        children with functional OAB and DUI, the bladder detrusor is overactive when performing a&#xD;
        urodynamic investigation, but this is not evident for all children suffering from OAB and&#xD;
        DUI. The etiology of OAB and DUI is not yet fully established and might be multifactorial.&#xD;
  &#xD;
        A few studies among adults have shown that adult women with OAB and DUI has more activity in&#xD;
        brain areas controlling the bladder compared to adult women without bladder symptoms.&#xD;
        Moreover, one study among adult women has shown a decrease in brain activity in areas&#xD;
        controlling the bladder after sacral TENS treatment. This has led to a hypothesis that&#xD;
        increased activity in the brain is a pathophysiological mechanism of OAB and DUI. Brain&#xD;
        activity among children with OAB and DUI has not yet been investigated.&#xD;
  &#xD;
        Therefore, the objectives of this study is:&#xD;
  &#xD;
          1. To investigate the activity in brain areas controlling the bladder among children with&#xD;
             OAB and DUI and age- and gender-matched children without bladder symptoms AND&#xD;
  &#xD;
          2. To investigate if sacral TENS has a centrally modulatory effect on the brain activity in&#xD;
             areas controlling the bladder among children with OAB and DUI.&#xD;
  &#xD;
        Methods: The study consists of two sub-studies. The first sub-study is a cross-sectional&#xD;
        study, whereas the second sub-study is an interventional cohort study. Forty-five children&#xD;
        with OAB and DUI and 20 healthy children without bladder symptoms will be recruited. The&#xD;
        study includes one structural MRI as well as two sessions of functional MRIs (only one&#xD;
        functional MRI for healthy participants), one session prior to and after 10 weeks of sacral&#xD;
        TENS treatment. The functional MRI session consist of a functional MRI with full bladder&#xD;
        followed by a functional MRI with empty bladder. Moreover, the study participants and/or&#xD;
        their parents are asked to fill in frequency and volume charts, Dry Pie, screening tools to&#xD;
        rule out attention deficit hyperactivity disorder and autism spectrum disorders, and quality&#xD;
        of life-questionnaires (WHO-5 and PinQ).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 5, 2021</start_date>
    <completion_date type="Anticipated">April 2024</completion_date>
    <primary_completion_date type="Anticipated">April 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Cross-sectional and interventional cohort study</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Activity in brain areas controlling the bladder</measure>
      <time_frame>Baseline</time_frame>
      <description>Blood Oxygen Level Dependent (BOLD)-signals on functional MRIs, compared between children with Overactive Bladder and Daytime Urinary Incontinence and children without bladder symptoms.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in activity in brain areas controlling the bladder after TENS-treatment</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Blood Oxygen Level Dependent (BOLD)-signals on functional MRIs, compared between responders and non-responders to TENS-treatment.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Structural differences on MRI among children with OAB and DUI and healthy children</measure>
      <time_frame>Baseline</time_frame>
      <description>Volume of brain areas involved in bladder control (e.g. lateral nuclei in pons, prefrontal cortex, anterior cingulate cortex (ACC), insula, periaqueductal grey (PAG), the pontine micturition center (PMC), and hypothalamus)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Differences in Quality of Life (QoL) between children with OAB and DUI and healthy children</measure>
      <time_frame>Baseline</time_frame>
      <description>Assessment of QoL using WHO-5 among children with OAB and DUI and compare to QoL among children without bladder symptoms.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in WHO-5 score among children with OAB and DUI at baseline and after the intervention.</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Assessment of QoL using WHO-5 among children with OAB and DUI prior to and after ten weeks of sacral TENS-treatment. WHO-5 (World Health Organization Quality of Life Brief Version) is a validated tool, assessing QoL as a total percent-score (range 0-100). A high score indicates better QoL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in PinQ score among children with OAB and DUI at baseline and after the intervention.</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Assessment of QoL using PinQ among children with OAB and DUI prior to and after ten weeks of sacral TENS treatment. PinQ (Pediatric Incontinence Questionnaire) is a validated tool, assessing QoL as a total score (range 0-80). A lower score indicates better QoL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in WHO-5 score among children with OAB and DUI compared among responders and non-responders to sacral TENS treatment.</measure>
      <time_frame>Immediately after the intervention</time_frame>
      <description>Assessment of QoL using WHO-5 and compare among responders and non-responders to sacral TENS-treatment. WHO-5 (World Health Organization Quality of Life Brief Version) is a validated tool, assessing QoL as a total percent-score (range 0-100). A high score indicates better QoL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in PinQ score among children with OAB and DUI compared among responders and non-responders to sacral TENS treatment.</measure>
      <time_frame>Immediately after the intervention</time_frame>
      <description>Assessment of QoL using PinQ and compare among responders and non-responders to sacral TENS-treatment. PinQ (Pediatric Incontinence Questionnaire) is a validated tool, assessing QoL as a total score (range 0-80). A lower score indicates better QoL.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Differences in maximum voided volume among responders and non-responders to sacral TENS treatment</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Differences in maximum voided volume (MVV) in milliliters as assessed by the frequency and volume chart, compared among responders and non-responders to sacral TENS treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Differences in voiding frequency among responders and non-responders to sacral TENS treatment</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Differences in voiding frequency as assessed by the frequency and volume chart, compared among responders and non-responders to sacral TENS treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Differences in VAS Urgency among responders and non-responders to sacral TENS treatment</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Differences in VAS Urgency (visual analogue scale for urgency) in percent with a higher percent indicating a higher degree of urgency, compared among responders and non-responders to sacral TENS treatment.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Differences in urinary incontinence severity scores among responders and non-responders to sacral TENS treatment</measure>
      <time_frame>Baseline AND immediately after the intervention</time_frame>
      <description>Differences in urinary incontinence severity scores as assessed by Dry Pie, compared among responders and non-responders to sacral TENS treatment.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">65</enrollment>
    <condition>Urinary Incontinence</condition>
    <condition>Daytime Wetting</condition>
    <condition>Urination Disorders</condition>
    <condition>Urination Involuntary</condition>
    <condition>Urologic Diseases</condition>
    <condition>Lower Urinary Tract Symptoms</condition>
    <condition>Urological Manifestations</condition>
    <condition>Behavioral Symptoms</condition>
    <condition>Mental Disorders</condition>
    <condition>Elimination Disorders</condition>
    <arm_group>
      <arm_group_label>Transcutaneous Electric Nerve Stimulation (TENS)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Sacral TENS</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sacral TENS</intervention_name>
      <description>Sacral TENS applied two hours daily for 10 weeks</description>
      <arm_group_label>Transcutaneous Electric Nerve Stimulation (TENS)</arm_group_label>
      <other_name>Urotherapy</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Overactive Bladder as per International Children's Continence Society criteria (cases&#xD;
               only).&#xD;
  &#xD;
            -  At least 2 incontinence episodes per week (cases only).&#xD;
  &#xD;
            -  No urinary tract symptoms (healthy participants only).&#xD;
  &#xD;
            -  More than 3 daily urinations.&#xD;
  &#xD;
            -  Normal clinical examination.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Known urogenital abnormality affecting the lower urinary tract function.&#xD;
  &#xD;
            -  Prior surgery in the urinary tract (except circumcision).&#xD;
  &#xD;
            -  Known neurological diseases or prior cerebral surgery.&#xD;
  &#xD;
            -  Known neuropsychiatric disorders or suspicion of those by screening.&#xD;
  &#xD;
            -  Treatment with pharmacological agents affecting the brain function.&#xD;
  &#xD;
            -  Prior treatment with Enuresis Alarm or Transcutaneous Electrical Nerve Stimulation.&#xD;
  &#xD;
            -  Prior or current treatment with mirabegron or oxybutynin.&#xD;
  &#xD;
            -  Current urinary tract infection.&#xD;
  &#xD;
            -  Current constipation according to Rome IV-criteria or faecal incontinence.&#xD;
  &#xD;
            -  Claustrophobia.&#xD;
  &#xD;
            -  Metallic items in the body contraindicating MRI-scans.&#xD;
  &#xD;
            -  Abnormal uroflowmetry (healthy participants only).&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>6 Years</minimum_age>
      <maximum_age>14 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Kristina Thorsteinsson, MD</last_name>
      <phone>+4597663372</phone>
      <email>uroforsk@rn.dk</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Søren Hagstrøm, MD, PhD</last_name>
      <phone>+4597663400</phone>
      <email>uroforsk@rn.dk</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Department of Pediatrics, Aalborg University Hospital</name>
        <address>
          <city>Aalborg</city>
          <zip>9000</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Kristina Thorsteinsson, MD</last_name>
        <phone>+4597660477</phone>
        <email>uroforsk@rn.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Department of Pediatrics, Aarhus University Hospital</name>
        <address>
          <city>Aarhus</city>
          <zip>8200</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Konstantinos Kamperis, MD, PhD</last_name>
        <phone>+4578430000</phone>
        <email>kostas.kamperis@clin.au.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Department of Pediatrics, Regional Hospital West Jutland</name>
        <address>
          <city>Herning</city>
          <zip>7400</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Luise Borch, MD, PhD</last_name>
        <email>luise.borch@rm.dk</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Department of Pediatrics, North Denmark Regional Hospital</name>
        <address>
          <city>Hjørring</city>
          <zip>9800</zip>
          <country>Denmark</country>
        </address>
      </facility>
      <status>Not yet recruiting</status>
      <contact>
        <last_name>Mette Line Roed, MD, PhD</last_name>
        <email>mld@rn.dk</email>
      </contact>
    </location>
    <location_countries>
      <country>Denmark</country>
    </location_countries>
    <reference>
      <citation>Warner TC, Baandrup U, Jacobsen R, Boggild H, Aunsholt Ostergaard PS, Hagstrom S. Prevalence of nocturia and fecal and urinary incontinence and the association to childhood obesity: a study of 6803 Danish school children. J Pediatr Urol. 2019 May;15(3):225.e1-225.e8. doi: 10.1016/j.jpurol.2019.02.004. Epub 2019 Feb 15.</citation>
      <PMID>30930018</PMID>
    </reference>
    <reference>
      <citation>von Gontard A, Overs C, Moritz AM, Thome-Granz S, Hussong J. Incontinence and headache in preschool children. Neurourol Urodyn. 2019 Nov;38(8):2280-2287. doi: 10.1002/nau.24134. Epub 2019 Aug 8.</citation>
      <PMID>31397011</PMID>
    </reference>
    <reference>
      <citation>Gur E, Turhan P, Can G, Akkus S, Sever L, Guzeloz S, Cifcili S, Arvas A. Enuresis: prevalence, risk factors and urinary pathology among school children in Istanbul, Turkey. Pediatr Int. 2004 Feb;46(1):58-63. doi: 10.1111/j.1442-200X.2004.01824.x.</citation>
      <PMID>15043666</PMID>
    </reference>
    <reference>
      <citation>Swithinbank LV, Heron J, von Gontard A, Abrams P. The natural history of daytime urinary incontinence in children: a large British cohort. Acta Paediatr. 2010 Jul;99(7):1031-6. doi: 10.1111/j.1651-2227.2010.01739.x. Epub 2010 Feb 25.</citation>
      <PMID>20199496</PMID>
    </reference>
    <reference>
      <citation>Xing D, Wang YH, Wen YB, Li Q, Feng JJ, Wu JW, Jia ZM, Yang J, Sihoe JD, Song CP, Hu HJ, Franco I, Wen JG. Prevalence and risk factors of overactive bladder in Chinese children: A population-based study. Neurourol Urodyn. 2020 Feb;39(2):688-694. doi: 10.1002/nau.24251. Epub 2019 Dec 5.</citation>
      <PMID>31804751</PMID>
    </reference>
    <reference>
      <citation>Chung JM, Lee SD, Kang DI, Kwon DD, Kim KS, Kim SY, Kim HG, Moon du G, Park KH, Park YH, Pai KS, Suh HJ, Lee JW, Cho WY, Ha TS, Han SW; Korean Enuresis Association. Prevalence and associated factors of overactive bladder in Korean children 5-13 years old: a nationwide multicenter study. Urology. 2009 Jan;73(1):63-7; discussion 68-9. doi: 10.1016/j.urology.2008.06.063. Epub 2008 Sep 30.</citation>
      <PMID>18829077</PMID>
    </reference>
    <reference>
      <citation>Franco I. Overactive bladder in children. Nat Rev Urol. 2016 Sep;13(9):520-32. doi: 10.1038/nrurol.2016.152. Epub 2016 Aug 17.</citation>
      <PMID>27530266</PMID>
    </reference>
    <reference>
      <citation>Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008 Jun;9(6):453-66. doi: 10.1038/nrn2401.</citation>
      <PMID>18490916</PMID>
    </reference>
    <reference>
      <citation>Griffiths D, Tadic SD. Bladder control, urgency, and urge incontinence: evidence from functional brain imaging. Neurourol Urodyn. 2008;27(6):466-74. doi: 10.1002/nau.20549.</citation>
      <PMID>18092336</PMID>
    </reference>
    <reference>
      <citation>Griffiths D, Tadic SD, Schaefer W, Resnick NM. Cerebral control of the bladder in normal and urge-incontinent women. Neuroimage. 2007 Aug 1;37(1):1-7. doi: 10.1016/j.neuroimage.2007.04.061. Epub 2007 May 18.</citation>
      <PMID>17574871</PMID>
    </reference>
    <reference>
      <citation>Weissbart SJ, Bhavsar R, Rao H, Wein AJ, Detre JA, Arya LA, Smith AL. Specific Changes in Brain Activity during Urgency in Women with Overactive Bladder after Successful Sacral Neuromodulation: A Functional Magnetic Resonance Imaging Study. J Urol. 2018 Aug;200(2):382-388. doi: 10.1016/j.juro.2018.03.129. Epub 2018 Apr 6.</citation>
      <PMID>29630979</PMID>
    </reference>
    <reference>
      <citation>Zuo L, Chen J, Wang S, Zhou Y, Wang B, Gu H. Intra- and inter-resting-state networks abnormalities in overactive bladder syndrome patients: an independent component analysis of resting-state fMRI. World J Urol. 2020 Apr;38(4):1027-1034. doi: 10.1007/s00345-019-02838-z. Epub 2019 Jun 6.</citation>
      <PMID>31172280</PMID>
    </reference>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>May 31, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Aalborg University Hospital</investigator_affiliation>
      <investigator_full_name>Kristina Thorsteinsson</investigator_full_name>
      <investigator_title>Principal Investigator</investigator_title>
    </responsible_party>
    <keyword>Transcutaneous Electrical Nerve Stimulation</keyword>
    <keyword>TENS</keyword>
    <keyword>Functional Magnetic Resonance Imaging</keyword>
    <keyword>fMRI</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Urinary Incontinence</mesh_term>
      <mesh_term>Enuresis</mesh_term>
      <mesh_term>Urinary Bladder, Overactive</mesh_term>
      <mesh_term>Urologic Diseases</mesh_term>
      <mesh_term>Urination Disorders</mesh_term>
      <mesh_term>Diurnal Enuresis</mesh_term>
      <mesh_term>Lower Urinary Tract Symptoms</mesh_term>
      <mesh_term>Urological Manifestations</mesh_term>
      <mesh_term>Mental Disorders</mesh_term>
      <mesh_term>Behavioral Symptoms</mesh_term>
      <mesh_term>Elimination Disorders</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05989646
  org study id: N-20210004
  nct id: NCT05989646
  lead sponsor: 
  collaborator: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The aim of this study is to investigate whether the activity in brain areas controlling the
        bladder is different among children suffering from Overactive Bladder (OAB) and Daytime
        Urinary Incontinence (DUI) compared to age- and gender-matched healthy children without
        bladder symptoms. Moreover, the aim is to investigate if sacral transcutaneous electric nerve
        stimulation (TENS) has a central mechanism of action. Children with OAB and DUI will be
        recruited from involved pediatric departments, and functional magnetic resonance imaging
        (fMRI) will be performed before and after 10 weeks of sacral TENS. In healthy children
        without bladder symptoms, only the baseline fMRI will be performed.
  Daytime Urinary Incontinence (DUI) is a common condition among children affecting 2.1-21.8 %
        of children aged 4.5-17 years. DUI is most often caused by a functional overactive bladder
        (OAB) leading to urgent desire to void (urgency) and frequent urinations (frequency). In some
        children with functional OAB and DUI, the bladder detrusor is overactive when performing a
        urodynamic investigation, but this is not evident for all children suffering from OAB and
        DUI. The etiology of OAB and DUI is not yet fully established and might be multifactorial.
  
        A few studies among adults have shown that adult women with OAB and DUI has more activity in
        brain areas controlling the bladder compared to adult women without bladder symptoms.
        Moreover, one study among adult women has shown a decrease in brain activity in areas
        controlling the bladder after sacral TENS treatment. This has led to a hypothesis that
        increased activity in the brain is a pathophysiological mechanism of OAB and DUI. Brain
        activity among children with OAB and DUI has not yet been investigated.
  
        Therefore, the objectives of this study is:
  
          1. To investigate the activity in brain areas controlling the bladder among children with
             OAB and DUI and age- and gender-matched children without bladder symptoms AND
  
          2. To investigate if sacral TENS has a centrally modulatory effect on the brain activity in
             areas controlling the bladder among children with OAB and DUI.
  
        Methods: The study consists of two sub-studies. The first sub-study is a cross-sectional
        study, whereas the second sub-study is an interventional cohort study. Forty-five children
        with OAB and DUI and 20 healthy children without bladder symptoms will be recruited. The
        study includes one structural MRI as well as two sessions of functional MRIs (only one
        functional MRI for healthy participants), one session prior to and after 10 weeks of sacral
        TENS treatment. The functional MRI session consist of a functional MRI with full bladder
        followed by a functional MRI with empty bladder. Moreover, the study participants and/or
        their parents are asked to fill in frequency and volume charts, Dry Pie, screening tools to
        rule out attention deficit hyperactivity disorder and autism spectrum disorders, and quality
        of life-questionnaires (WHO-5 and PinQ).
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Cross-sectional and interventional cohort study
  primary purpose: Basic Science
  masking: None (Open Label)
  measure: Activity in brain areas controlling the bladder
  time frame: Baseline
  description: Blood Oxygen Level Dependent (BOLD)-signals on functional MRIs, compared between children with Overactive Bladder and Daytime Urinary Incontinence and children without bladder symptoms.
  measure: Change in activity in brain areas controlling the bladder after TENS-treatment
  time frame: Baseline AND immediately after the intervention
  description: Blood Oxygen Level Dependent (BOLD)-signals on functional MRIs, compared between responders and non-responders to TENS-treatment.
  measure: Structural differences on MRI among children with OAB and DUI and healthy children
  time frame: Baseline
  description: Volume of brain areas involved in bladder control (e.g. lateral nuclei in pons, prefrontal cortex, anterior cingulate cortex (ACC), insula, periaqueductal grey (PAG), the pontine micturition center (PMC), and hypothalamus)
  measure: Differences in Quality of Life (QoL) between children with OAB and DUI and healthy children
  time frame: Baseline
  description: Assessment of QoL using WHO-5 among children with OAB and DUI and compare to QoL among children without bladder symptoms.
  measure: Change in WHO-5 score among children with OAB and DUI at baseline and after the intervention.
  time frame: Baseline AND immediately after the intervention
  description: Assessment of QoL using WHO-5 among children with OAB and DUI prior to and after ten weeks of sacral TENS-treatment. WHO-5 (World Health Organization Quality of Life Brief Version) is a validated tool, assessing QoL as a total percent-score (range 0-100). A high score indicates better QoL.
  measure: Change in PinQ score among children with OAB and DUI at baseline and after the intervention.
  time frame: Baseline AND immediately after the intervention
  description: Assessment of QoL using PinQ among children with OAB and DUI prior to and after ten weeks of sacral TENS treatment. PinQ (Pediatric Incontinence Questionnaire) is a validated tool, assessing QoL as a total score (range 0-80). A lower score indicates better QoL.
  measure: Change in WHO-5 score among children with OAB and DUI compared among responders and non-responders to sacral TENS treatment.
  time frame: Immediately after the intervention
  description: Assessment of QoL using WHO-5 and compare among responders and non-responders to sacral TENS-treatment. WHO-5 (World Health Organization Quality of Life Brief Version) is a validated tool, assessing QoL as a total percent-score (range 0-100). A high score indicates better QoL.
  measure: Change in PinQ score among children with OAB and DUI compared among responders and non-responders to sacral TENS treatment.
  time frame: Immediately after the intervention
  description: Assessment of QoL using PinQ and compare among responders and non-responders to sacral TENS-treatment. PinQ (Pediatric Incontinence Questionnaire) is a validated tool, assessing QoL as a total score (range 0-80). A lower score indicates better QoL.
  measure: Differences in maximum voided volume among responders and non-responders to sacral TENS treatment
  time frame: Baseline AND immediately after the intervention
  description: Differences in maximum voided volume (MVV) in milliliters as assessed by the frequency and volume chart, compared among responders and non-responders to sacral TENS treatment.
  measure: Differences in voiding frequency among responders and non-responders to sacral TENS treatment
  time frame: Baseline AND immediately after the intervention
  description: Differences in voiding frequency as assessed by the frequency and volume chart, compared among responders and non-responders to sacral TENS treatment.
  measure: Differences in VAS Urgency among responders and non-responders to sacral TENS treatment
  time frame: Baseline AND immediately after the intervention
  description: Differences in VAS Urgency (visual analogue scale for urgency) in percent with a higher percent indicating a higher degree of urgency, compared among responders and non-responders to sacral TENS treatment.
  measure: Differences in urinary incontinence severity scores among responders and non-responders to sacral TENS treatment
  time frame: Baseline AND immediately after the intervention
  description: Differences in urinary incontinence severity scores as assessed by Dry Pie, compared among responders and non-responders to sacral TENS treatment.
  arm group label: Transcutaneous Electric Nerve Stimulation (TENS)
  arm group type: Experimental
  description: Sacral TENS
  intervention type: Device
  intervention name: Sacral TENS
  description: Sacral TENS applied two hours daily for 10 weeks
  arm group label: Transcutaneous Electric Nerve Stimulation (TENS)
  other name: Urotherapy
  criteria: 
  gender: All
  minimum age: 6 Years
  maximum age: 14 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Kristina Thorsteinsson, MD
  phone: +4597663372
  email: uroforsk@rn.dk
  last name: Søren Hagstrøm, MD, PhD
  phone: +4597663400
  email: uroforsk@rn.dk
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  facility: 
  status: Not yet recruiting
  contact: 
  country: Denmark
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  PMID: 30930018
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  PMID: 31397011
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  PMID: 20199496
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  PMID: 31172280
  responsible party type: Principal Investigator
  investigator affiliation: Aalborg University Hospital
  investigator full name: Kristina Thorsteinsson
  investigator title: Principal Investigator
  mesh term: Urinary Incontinence
  mesh term: Enuresis
  mesh term: Urinary Bladder, Overactive
  mesh term: Urologic Diseases
  mesh term: Urination Disorders
  mesh term: Diurnal Enuresis
  mesh term: Lower Urinary Tract Symptoms
  mesh term: Urological Manifestations
  mesh term: Mental Disorders
  mesh term: Behavioral Symptoms
  mesh term: Elimination Disorders