<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/NCT03819062</url>
  </required_header>
  <id_info>
    <org_study_id>McMasterChenC</org_study_id>
    <nct_id>NCT03819062</nct_id>
  </id_info>
  <brief_title>Sacral Neuromodulation as Treatment for Chronic Constipation</brief_title>
  <official_title>Sacral Neuromodulation as Treatment for Chronic Constipation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>McMaster University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>McMaster University</source>
  <oversight_info>
    <has_dmc>No</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 objective of this study is to study if low level laser therapy will do more good than&#xD;
      harm for patients with severe chronic refractory constipation. It is a proof of concept study&#xD;
      without a placebo arm.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be offered the therapy if High-Resolution Colonic Manometry has shown that&#xD;
      coordination between colon motility and recto-anal activity is abnormal and that autonomic&#xD;
      nervous system assessment suggests a dysfunction of communication between the spinal cord&#xD;
      autonomic nerves and the colon-rectum-anus. The therapy consists of a 3 week treatment with a&#xD;
      total of 8 sessions of low level laser therapy. Effects will be assessed using symptom and&#xD;
      quality of life questionnaires and physiological assessments of colon and pelvic floor&#xD;
      function, at 4 weeks and 12 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 8, 2019</start_date>
  <completion_date type="Anticipated">February 1, 2027</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2025</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>proof of concept</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in number of bowel movements/week</measure>
    <time_frame>12 weeks</time_frame>
    <description>(significance level P&lt;0.05 comparing before and after).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms using the questionnaire PAC-SYM</measure>
    <time_frame>4 weeks</time_frame>
    <description>The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum important difference indicating clinically significant improvement is minus 0.6 (Saito &amp; Camilleri, 2018)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms using the questionnaire PAC-SYM</measure>
    <time_frame>12 weeks</time_frame>
    <description>The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum important difference indicating clinically significant improvement is minus 0.6 (Saito &amp; Camilleri, 2018)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life assessed by questionnaire PAC-QOL</measure>
    <time_frame>4 weeks</time_frame>
    <description>The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum difference indicating clinically significant improvement is -0.5 (Marquis et al., 2005)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in quality of life assessed by questionnaire PAC-QOL</measure>
    <time_frame>12 weeks</time_frame>
    <description>The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum difference indicating clinically significant improvement is -0.5 (Marquis et al., 2005)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autonomic function assessment</measure>
    <time_frame>4 weeks</time_frame>
    <description>Increase or decrease in parasympathetic reactivity in response to a change in body position from supine to standing expressed as Respiratory Sinus Arrhythmia (ln(ms2)); comparison before and after treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Anal spincter pressure</measure>
    <time_frame>4 weeks</time_frame>
    <description>Anorectal manometry, measuring resting anal sphincter pressure in mmHg; comparison before and after treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in anal sphincter pressure due to attempting defecation</measure>
    <time_frame>4 weeks</time_frame>
    <description>Anorectal manometry, measuring change in resting anal sphincter pressure in mmHg; comparison before and after treatment</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Chronic Constipation</condition>
  <arm_group>
    <arm_group_label>Refractory Constipation with LLLT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low level laser therapy (LLLT) will be administered to patients with severe refractory chronic constipation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Low Level Laser Therapy</intervention_name>
    <description>A 3 week treatment period with 8 treatment sessions in total.</description>
    <arm_group_label>Refractory Constipation with LLLT</arm_group_label>
    <other_name>Sacral Neuromodulation</other_name>
    <other_name>Photobiomodulation</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with severe chronic refractory constipation&#xD;
&#xD;
          -  Must have undergone high resolution colonic manometry that shows abnormal coordination&#xD;
             between colonic motility and ano-rectal function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant patients&#xD;
&#xD;
          -  Known malignancies in the area of treatment&#xD;
&#xD;
          -  Active bleeding in area of treatment&#xD;
&#xD;
          -  Active deep vein thrombosis&#xD;
&#xD;
          -  When tatoos are present at area of treatment&#xD;
&#xD;
          -  Patients that are light sensitive&#xD;
&#xD;
          -  Patients who take NSAIDS or steroids.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jihong Chen, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>McMaster University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jihong Chen, MD PhD</last_name>
    <phone>2263439909</phone>
    <email>chen338@mcmaster.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Jan D Huizinga, PhD</last_name>
    <phone>2263438888</phone>
    <email>huizinga@mcmaster.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>McMaster University</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8N3Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jihong Chen, MD PhD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <reference>
    <citation>Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005 May;40(5):540-51. doi: 10.1080/00365520510012208.</citation>
    <PMID>16036506</PMID>
  </reference>
  <reference>
    <citation>Saito YA, Camilleri M. Editorial: patient assessment of constipation-symptoms (PAC-SYM) questionnaire has a minimal important difference. Aliment Pharmacol Ther. 2018 Jan;47(1):138-139. doi: 10.1111/apt.14389. No abstract available.</citation>
    <PMID>29226416</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>January 16, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>April 4, 2022</last_update_submitted>
  <last_update_submitted_qc>April 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>McMaster University</investigator_affiliation>
    <investigator_full_name>Jihong Chen</investigator_full_name>
    <investigator_title>Assistant Professor</investigator_title>
  </responsible_party>
  <keyword>Constipation</keyword>
  <keyword>spinal cord injury</keyword>
  <keyword>back pain</keyword>
  <keyword>High-Resolution Colonic Manometry</keyword>
  <keyword>Anorectal Manometry</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</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/NCT03819062
org study id: McMasterChenC
nct id: NCT03819062
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of this study is to study if low level laser therapy will do more good than
      harm for patients with severe chronic refractory constipation. It is a proof of concept study
      without a placebo arm.
Patients will be offered the therapy if High-Resolution Colonic Manometry has shown that
      coordination between colon motility and recto-anal activity is abnormal and that autonomic
      nervous system assessment suggests a dysfunction of communication between the spinal cord
      autonomic nerves and the colon-rectum-anus. The therapy consists of a 3 week treatment with a
      total of 8 sessions of low level laser therapy. Effects will be assessed using symptom and
      quality of life questionnaires and physiological assessments of colon and pelvic floor
      function, at 4 weeks and 12 weeks.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: proof of concept
primary purpose: Treatment
masking: None (Open Label)
measure: Change in number of bowel movements/week
time frame: 12 weeks
description: (significance level P<0.05 comparing before and after).
measure: Change in symptoms using the questionnaire PAC-SYM
time frame: 4 weeks
description: The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum important difference indicating clinically significant improvement is minus 0.6 (Saito & Camilleri, 2018)
measure: Change in symptoms using the questionnaire PAC-SYM
time frame: 12 weeks
description: The PAC-SYM questionnaire is a 12-item questionnaire that evaluates the severity of symptoms of constipation in 3 domains (stool, rectal, and abdominal symptoms) on a 5-point Likert scale ranging from 0 (absent) to 4 (very severe). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items (ie, symptoms). The range of the domain or total score is 0 (response is 'absent' for each item) to 4 (response is 'very severe' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum important difference indicating clinically significant improvement is minus 0.6 (Saito & Camilleri, 2018)
measure: Change in quality of life assessed by questionnaire PAC-QOL
time frame: 4 weeks
description: The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum difference indicating clinically significant improvement is -0.5 (Marquis et al., 2005)
measure: Change in quality of life assessed by questionnaire PAC-QOL
time frame: 12 weeks
description: The PAC-QOL scale is a 28-item self-report instrument designed to evaluate the burden of constipation on patients' everyday functioning and well-being. Each item is rated on a 5-point Likert scale ranging from 0 (not at all) to 4 (extremely). The instrument can be used to generate an overall score, but is also reported to assess 4 specific constipation-related domains including: 1) Worries and concerns (11 items), 2) Physical discomfort (4 items), 3) Psychosocial discomfort (8 items), and 4) Satisfaction (5 items). Each domain score is the mean of the non-missing items for that domain. The total score is the mean of all non-missing items. The range of the domain or total score is 0 (response is 'not at all' for each item) to 4 (response is 'extremely' for each item). A negative change from baseline indicates improvement, a positive change indicates worsening of symptoms. The minimum difference indicating clinically significant improvement is -0.5 (Marquis et al., 2005)
measure: Autonomic function assessment
time frame: 4 weeks
description: Increase or decrease in parasympathetic reactivity in response to a change in body position from supine to standing expressed as Respiratory Sinus Arrhythmia (ln(ms2)); comparison before and after treatment
measure: Anal spincter pressure
time frame: 4 weeks
description: Anorectal manometry, measuring resting anal sphincter pressure in mmHg; comparison before and after treatment.
measure: Change in anal sphincter pressure due to attempting defecation
time frame: 4 weeks
description: Anorectal manometry, measuring change in resting anal sphincter pressure in mmHg; comparison before and after treatment
arm group label: Refractory Constipation with LLLT
arm group type: Experimental
description: Low level laser therapy (LLLT) will be administered to patients with severe refractory chronic constipation
intervention type: Device
intervention name: Low Level Laser Therapy
description: A 3 week treatment period with 8 treatment sessions in total.
arm group label: Refractory Constipation with LLLT
other name: Sacral Neuromodulation
other name: Photobiomodulation
criteria: 
gender: All
minimum age: 6 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jihong Chen, MD PhD
role: Principal Investigator
affiliation: McMaster University
last name: Jihong Chen, MD PhD
phone: 2263439909
email: chen338@mcmaster.ca
last name: Jan D Huizinga, PhD
phone: 2263438888
email: huizinga@mcmaster.ca
facility: 
status: Recruiting
contact: 
country: Canada
citation: Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol. 2005 May;40(5):540-51. doi: 10.1080/00365520510012208.
PMID: 16036506
citation: Saito YA, Camilleri M. Editorial: patient assessment of constipation-symptoms (PAC-SYM) questionnaire has a minimal important difference. Aliment Pharmacol Ther. 2018 Jan;47(1):138-139. doi: 10.1111/apt.14389. No abstract available.
PMID: 29226416
responsible party type: Principal Investigator
investigator affiliation: McMaster University
investigator full name: Jihong Chen
investigator title: Assistant Professor
mesh term: Constipation
sharing ipd: Undecided