<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/NCT03797586</url>
  </required_header>
  <id_info>
    <org_study_id>2018-164-KY-01</org_study_id>
    <nct_id>NCT03797586</nct_id>
  </id_info>
  <brief_title>Effect of Electroacupuncture on Opioid-induced Constipation in Patients With Cancer</brief_title>
  <official_title>Effect of Electroacupuncture on Opioid-induced Constipation in Patients With Cancer: Study Protocol for a Multicenter Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Guang'anmen Hospital of China Academy of Chinese Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Guang'anmen Hospital of China Academy of Chinese Medical Sciences</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>
      Approximately 70-80% of patients with advanced disease will be affected by moderate to severe&#xD;
      pain. Opioid analgesics represented by morphine and oxycodone are the cornerstone of&#xD;
      cancer-pain management, and recommended for use in the management of moderate to severe&#xD;
      cancer pain according to WHO Cancer Pain Relief Guidelines. One view is that a trial of&#xD;
      systemic opioid therapy should be administered to all cancer patients with pain of moderate&#xD;
      or greater severity regardless of the pain mechanism. Although opioids analgesics do work&#xD;
      well as relieving pain and improving quality of life via their action at opioid receptors in&#xD;
      the central nervous system (CNS) and the peripheral nervous system, they also have powerful&#xD;
      adverse effects. The overall occurrence of opioid-related adverse drug events has ranged&#xD;
      from1.8% to 13.6%. Opioid-induced constipation (OIC), one of the most prevalent adverse&#xD;
      events (AEs) in patients receiving opioid analgesics, defined as a change in baseline bowel&#xD;
      habits or defecatory patterns following initiation, alteration, or increase in opioid&#xD;
      therapy. The prevalence of OIC has been estimated to affect 41% of patients with chronic&#xD;
      noncancer pain taking opioids and 94% of cancer patients taking opioids for pain. Unlike many&#xD;
      other opioid-related AEs, OIC is persistent and rarely tolerated. OIC impacts pain control,&#xD;
      patients' quality of life and may cause patients to reduce the dose or discontinue opioid&#xD;
      use.&#xD;
&#xD;
      Acupuncture, a traditional Chinese medicine, has been used to treat gastrointestinal disease&#xD;
      including constipation for thousands of years. Two systematic reviews concluded that&#xD;
      acupuncture can improve spontaneous bowel movements for functional constipation, and our&#xD;
      recent study indicated that electroacupuncture(EA) could increase complete spontaneous bowel&#xD;
      movements and is safe for chronic severe functional constipation. Acupuncture could improve&#xD;
      gastrointestinal function via facilitating gastrointestinal motility. Currently, there is&#xD;
      little detailed information available regarding the acupuncture use for OIC. The objective of&#xD;
      this study is to assess the efficacy and safety of EA for OIC in patients with cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2019</start_date>
  <completion_date type="Actual">December 11, 2021</completion_date>
  <primary_completion_date type="Actual">October 16, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The proportion of responders</measure>
    <time_frame>weeks 1-8</time_frame>
    <description>A responder is defined as a patient that has at least three spontaneous bowel movements (SBMs) per week and an increase of at least one SBM a week from the baseline for at least 6 of the 8 weeks of the treatment period.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16.</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with ≥3 mean weekly spontaneous bowel movements (SBMs) during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with an increase of ≥1 mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A Change in the mean weekly complete spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16.</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with ≥3 mean weekly spontaneous bowel movements (CSBMs) during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients with an increase of ≥1 mean weekly spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A change in the mean Bristol Stool Form Scale score for stool consistency of spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>For stool consistency, each patient was asked to record their stool consistency according to the Bristol Stool Form Scale, on the following seven points scale. (scored from 1 to 7 for stool types 1 to 7, respectively)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A change in the mean score for the straining of spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16</measure>
    <time_frame>weeks 1-8, and weeks 13-16</time_frame>
    <description>For assessment of straining of SBM, each patient was asked to rate his/her score for straining using the following five-point scale: not at all difficulty (0), a little bit difficulty (1), moderately difficulty (2), quite a bit difficulty (3), extremely difficulty (4).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A change in the total and subscale score of the Patient Assessment of Constipation-Symptom (PAC-SYM) questionnaire from baseline at weeks 8 and 16</measure>
    <time_frame>week 8 and week 16</time_frame>
    <description>The PAC-SYM is a 12-item evaluative questionnaire for the chronic constipation, which consists of 4-item abdominal, 3-item rectal, and 5-item stool subscales. Each item score ranges from 0 to 4 in the 2 weeks (14 days) prior to assessment. The, where 0 = symptom absent, 1 = mild,2 = moderate,3 = severe and 4 = very severe. Lower scores indicate a lower symptom burden. Each subscale score will be calculated as the mean of the completed items for that subscale. The total score will be calculated as the mean of all completed items.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>A change in the total and subscale scores of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires from the baseline at weeks 8 and 16</measure>
    <time_frame>week 8 and week 16</time_frame>
    <description>The PAC-QOL is a 28-item self-reported instrument for assessing the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. It is divided into four subscales: physical discomfort (items 1-4), psychosocial discomfort (items 5-12), worries/concerns (items 13-23), and satisfaction (items 24 to 28). Each of the item scores ranges from 0 (not at all) to 4 (extremely), with lower scores indicating a better quality of life. For each visit, individual subscale scores will be calculated as the mean of the completed items for that subscale.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patients' global assessment of treatment efficacy</measure>
    <time_frame>week 8 and week 16</time_frame>
    <description>each patient was asked to rate his/her efficacy of treatment using the following 7-point self-reporting scale: markedly worse (1), moderately worse (2),slightly worse (3), no change (4), slightly improved (5), moderately improved (6), markedly improved (7).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of patients using rescue medicine and the mean frequency of rescue medicine use per week during weeks 1-8 and weeks 9-16</measure>
    <time_frame>weeks 1-8, and weeks 9-16</time_frame>
    <description>The proportion of patients using rescue medicine will be compared between groups during weeks 1-8, and weeks 9-16. The mean frequency of using rescue medicine per week during weeks 1-8 equals the total of rescue medicine consumption divided by 8. The mean frequency of using rescue medicine per week during weeks 9-16 equals the total of rescue medicine consumption divided by 8.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Patients'expectation of the acupuncture efficacy</measure>
    <time_frame>at baseline</time_frame>
    <description>Participants will be asked to answer the following questions before the intervention: &quot;Do you think acupuncture will be effective in treating the disease in general?&quot; &quot;Do you think acupuncture will be effective in improving the OIC?&quot; and &quot;which acupuncture modalities do you prefer, EA or SA?&quot; For each question, patients will choose one of the following answers: &quot;unclear/whatever&quot;, &quot;EA&quot;, or &quot;SA&quot;</description>
  </other_outcome>
  <other_outcome>
    <measure>The patient blinding assessment</measure>
    <time_frame>at week 8</time_frame>
    <description>Five minutes after the end of any treatment in the eighth week the patients will be asked to answer the following question: &quot;Is traditional EA the acupuncture modality that you have received?&quot;.</description>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>week 1 to week 16</time_frame>
    <description>All adverse events (AEs) t will be recorded throughout the whole trial in case report form. AEs will be categorized as treatment-related (e.g., broken needle, dizziness, fainting, localized hematoma, localized infection or abscess, or some discomforts after acupuncture) and non-treatment-related. Detailed information regarding AEs and serious adverse events (SAEs)-including the name, onset and end date, intensity, relationship with acupuncture and outcome-will be recorded.</description>
  </other_outcome>
  <other_outcome>
    <measure>The intensity of cancerous pain evaluation</measure>
    <time_frame>at baseline, at weeks 2, 4, 6, 8 and 16.</time_frame>
    <description>The mean cancerous pain intensity and worst cancerous pain intensity during the preceding week will be evaluated by 11 grades (from &quot;0=no pain&quot; to &quot;10=worst pain (the strongest pain ever experienced)&quot; at baseline, as well as weeks 2, 4, 6, 8 and 16.</description>
  </other_outcome>
  <other_outcome>
    <measure>The proportion of patients discontinuing the opioid, and those with a ≥30% weekly mean increase or decrease in the dose of opioid from baseline during weeks 1-8 and weeks 9-16</measure>
    <time_frame>at week 8 and week 16</time_frame>
    <description>The proportion of patients discontinuing the opioid, and those with increase/decrease from baseline of ≥30% opioid usage per week will be compared between groups during weeks 1-8, and weeks 9-16</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">100</enrollment>
  <condition>Opioid-induced Constipation in Patients With Cancer</condition>
  <arm_group>
    <arm_group_label>Electroacupuncture group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Bilateral ST25,SP14, ST37 will be used in the EA group. For ST25 and SP14, 0.30×50mm or 0.30×75mm needles will be vertically inserted to the muscle layer of the abdominal , where patients will feel sharp pain and acupuncturists will feel resistance from the needle tip. For ST37, 0.30×40 mm needles will be vertically inserted approximately 15 mm deep, followed by three-time manipulation of even lifting and twisting method to elicit the sensation of deqi. Then paired alligator clips of the EA apparatus will be attached to the needle holders of the bilateral ST25, SP14, and ST37. EA stimulation will be retained for 30 minutes with a continuous wave of 10 Hz and current intensity of 0.5 to 4 mA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham electroacupuncture group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Bilateral sham ST25, SP14, and ST37 will be used in the SA group. After sterilizing the skin, 0.30×40mm needles will be straightly inserted at the sham points about 2-3mm until they can be fixed on the skin when attached by the alligator clips. No manipulation will be used, and no deqi sensation are elicited for all sham points. The bilateral sham ST25, SP14, and ST37 points will be attached by the same EA apparatus with a continuous wave of 10 Hz and current intensity of 0.1 to 0.2 mA for 30 minutes with only the initial 30 seconds on.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Electroacupuncture group</intervention_name>
    <description>Bilateral Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37) will be used in the EA group. With the local skin of the patients was routinely sterilized in a prone position in relaxation, acupuncturists will insert needles into the acupuncture points. For ST25 and SP14, 0.30×50mm or 0.30×75mm needles will be vertically inserted to the muscle layer of the abdominal wall, where participants will feel sharp pain and acupuncturists will feel resistance from the needle tip. For ST37, 0.30×40 mm needles will be vertically inserted approximately 15 mm deep, followed by three-time manipulation of even lifting and twisting method to elicit the sensation of deqi. Then paired alligator clips of the EA apparatus will be attached to the needle holders of the bilateral ST25, SP14, and ST37. EA stimulation will be retained for 30 minutes with a continuous wave of 10 Hz and current intensity of 0.5 to 4 mA.</description>
    <arm_group_label>Electroacupuncture group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Sham electroacupuncture group</intervention_name>
    <description>Bilateral sham ST25, SP14, and ST37 will be used in the SA group. After sterilizing the skin, 0.30×40mm needles will be straightly inserted at the sham points about 2-3mm until they can be fixed on the skin when attached by the alligator clips. No manipulation will be used, and no deqi sensation are elicited for all sham points. The bilateral sham ST25, SP14, and ST37 points will be attached by the same EA apparatus with a continuous wave of 10 Hz and current intensity of 0.1 to 0.2 mA for 30 minutes with only the initial 30 seconds on.</description>
    <arm_group_label>Sham electroacupuncture group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Cancer patients who conformed to all the following conditions will be further screened for&#xD;
        eligibility:&#xD;
&#xD;
          1. Cancer patients must meet the Rome IV[1] diagnostic criteria for OIC: New or worsening&#xD;
             symptoms of constipation following initiation, alteration, or increase in opioid&#xD;
             treatment. For patients with a history of chronic functional constipation, he/she must&#xD;
             have worsening symptoms of constipation when the opioid therapy is initiated, changed,&#xD;
             or the dose is increased;&#xD;
&#xD;
          2. Patients recruited in this trial must have a history of OIC symptoms for at least 1&#xD;
             week;&#xD;
&#xD;
          3. Patients must be ≥18 years of age and ≤85 years of age;&#xD;
&#xD;
          4. Patient's cancer condition must be stable with a life expectancy that is more than six&#xD;
             months;&#xD;
&#xD;
          5. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of&#xD;
             0-3;&#xD;
&#xD;
          6. Patients must have been receiving a relatively stable maintained opioid regimen,&#xD;
             consisting of a total daily dose of 30 mg to 1000 mg oral morphine equivalents for at&#xD;
             least 2 weeks prior to screening for cancer pain. Furthermore, it must be anticipated&#xD;
             that the opioid will be maintained for at least 10 weeks;&#xD;
&#xD;
          7. The SBM frequency of the patients must be ≤ 2 times a week when laxatives are not&#xD;
             being taken;&#xD;
&#xD;
          8. Patients must be capable of oral intake of drugs, food and beverages;&#xD;
&#xD;
          9. Provision of written informed consent before participation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants who fulfill any of the following criteria will be excluded:&#xD;
&#xD;
          1. Patients diagnosed with clinically significant abnormal defecation due to structural&#xD;
             abnormalities of the gastrointestinal tract and other tissues related to&#xD;
             gastrointestinal tract (not including OIC): inflammatory bowel disease, rectal&#xD;
             prolapse, gastrointestinal obstruction, peritoneal metastasis, or peritoneal tumor at&#xD;
             the time of enrollment;&#xD;
&#xD;
          2. Patients with a history of gastrointestinal tract operation, abdominal operation, or&#xD;
             abdominal adhesion within one month prior to screening; history of intestinal&#xD;
             obstruction within three months prior to screening;&#xD;
&#xD;
          3. Diagnosis of active diverticular disease; or severe hemorrhoid; or anal fissure; or&#xD;
             artificial rectum or anus;&#xD;
&#xD;
          4. Patients with an intraperitoneal catheter or a feeding tube;&#xD;
&#xD;
          5. Diagnosis of pelvic disorder which are considered to have obvious effects on the&#xD;
             intestinal transport of feces (such as uterine prolapse ≥degree 2, uterine fibroids&#xD;
             [located in the posterior of the uterus with a diameter ≥ 5 cm] affecting bowel&#xD;
             movement);&#xD;
&#xD;
          6. Patients that are being treated with a new cancer chemotherapy, which had never been&#xD;
             administered in the past, within 14 days of the screening or are scheduled to receive&#xD;
             such therapy during the study;&#xD;
&#xD;
          7. Patients that received radiotherapy within 28 days of the screening or are scheduled&#xD;
             to receive such therapy during the study;&#xD;
&#xD;
          8. Patients that underwent a surgery or intervention that is considered to have an&#xD;
             obvious effect on the gastrointestinal functions within 28 days of the screening or&#xD;
             are scheduled to receive surgery or intervention which is considered to have obvious&#xD;
             effects on the gastrointestinal functions during the study, or scheduled to receive&#xD;
             surgery or intervention which will be anticipated to prevent the patients from&#xD;
             completing the trial;&#xD;
&#xD;
          9. Patients with uncontrolled hyperthyroidism, severe hypertension, heart disease,&#xD;
             systematic infection or blood coagulation disorders (hypercoagulation status or&#xD;
             hemorrhagic tendency) at the time of study inclusion;&#xD;
&#xD;
         10. Patients that consumed &gt;4 additional opioid doses per day, for breakthrough pain, for&#xD;
             more than 3 days during the baseline period, or if their maintenance opioid dosing&#xD;
             regimen was modified during this period;&#xD;
&#xD;
         11. Patients with severe cancerous pain (e.g., typical average daily pain intensity rating&#xD;
             of 7 to 10 on a numerical rating scales (NRS; 0 [no pain] to 10 [the worst pain&#xD;
             possible]) after the use of routine dose and frequency of opioids) refractory to&#xD;
             opioid therapy;&#xD;
&#xD;
         12. Patients with a history of opioid discontinuation due to severe adverse events or&#xD;
             patients that are expected to discontinue opioid use due to the potential risk of&#xD;
             adverse events;&#xD;
&#xD;
         13. Patients that received an opioid receptor antagonist within one month of the&#xD;
             screening, or those who are scheduled to receive such therapy during the study;&#xD;
&#xD;
         14. Patients with a history of nerve neurolysis;&#xD;
&#xD;
         15. Patients with severe cognitive impairment, aphasia, or psychiatric disorders;&#xD;
             abdominal aortic aneurysm; hepatomegaly(liver span &gt; 14cm at the mid-clavicular line&#xD;
             by ultrasound examination); or splenomegaly (spleen length [cranial to caudal] &gt; 13cm&#xD;
             by ultrasound examination);&#xD;
&#xD;
         16. Patients that have received acupuncture within three months of the screening;&#xD;
&#xD;
         17. Other patients who are considered ineligible for the study by the investigator on the&#xD;
             basis of concomitant therapy and medical findings.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhishun Liu</last_name>
    <role>Study Chair</role>
    <affiliation>China Academy of Chinese Medicine Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Guang An Men Hospital</name>
      <address>
        <city>Beijing</city>
        <zip>100053</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2022</verification_date>
  <study_first_submitted>January 5, 2019</study_first_submitted>
  <study_first_submitted_qc>January 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>July 3, 2022</last_update_submitted>
  <last_update_submitted_qc>July 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Guang'anmen Hospital of China Academy of Chinese Medical Sciences</investigator_affiliation>
    <investigator_full_name>Liu Zhishun</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>electroacupuncture；opioid-induced constipation ,cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Constipation</mesh_term>
    <mesh_term>Opioid-Induced Constipation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 7, 2022</submitted>
    <returned>July 7, 2023</returned>
    <submitted>July 28, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03797586
org study id: 2018-164-KY-01
nct id: NCT03797586
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Approximately 70-80% of patients with advanced disease will be affected by moderate to severe
      pain. Opioid analgesics represented by morphine and oxycodone are the cornerstone of
      cancer-pain management, and recommended for use in the management of moderate to severe
      cancer pain according to WHO Cancer Pain Relief Guidelines. One view is that a trial of
      systemic opioid therapy should be administered to all cancer patients with pain of moderate
      or greater severity regardless of the pain mechanism. Although opioids analgesics do work
      well as relieving pain and improving quality of life via their action at opioid receptors in
      the central nervous system (CNS) and the peripheral nervous system, they also have powerful
      adverse effects. The overall occurrence of opioid-related adverse drug events has ranged
      from1.8% to 13.6%. Opioid-induced constipation (OIC), one of the most prevalent adverse
      events (AEs) in patients receiving opioid analgesics, defined as a change in baseline bowel
      habits or defecatory patterns following initiation, alteration, or increase in opioid
      therapy. The prevalence of OIC has been estimated to affect 41% of patients with chronic
      noncancer pain taking opioids and 94% of cancer patients taking opioids for pain. Unlike many
      other opioid-related AEs, OIC is persistent and rarely tolerated. OIC impacts pain control,
      patients' quality of life and may cause patients to reduce the dose or discontinue opioid
      use.

      Acupuncture, a traditional Chinese medicine, has been used to treat gastrointestinal disease
      including constipation for thousands of years. Two systematic reviews concluded that
      acupuncture can improve spontaneous bowel movements for functional constipation, and our
      recent study indicated that electroacupuncture(EA) could increase complete spontaneous bowel
      movements and is safe for chronic severe functional constipation. Acupuncture could improve
      gastrointestinal function via facilitating gastrointestinal motility. Currently, there is
      little detailed information available regarding the acupuncture use for OIC. The objective of
      this study is to assess the efficacy and safety of EA for OIC in patients with cancer.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: The proportion of responders
time frame: weeks 1-8
description: A responder is defined as a patient that has at least three spontaneous bowel movements (SBMs) per week and an increase of at least one SBM a week from the baseline for at least 6 of the 8 weeks of the treatment period.
measure: Change in the mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16.
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.
measure: The proportion of patients with ≥3 mean weekly spontaneous bowel movements (SBMs) during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.
measure: The proportion of patients with an increase of ≥1 mean weekly spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM.
measure: A Change in the mean weekly complete spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16.
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.
measure: The proportion of patients with ≥3 mean weekly spontaneous bowel movements (CSBMs) during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.
measure: The proportion of patients with an increase of ≥1 mean weekly spontaneous bowel movements (CSBMs) from the baseline during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: An SBM was defined as a bowel movement that occurred without any medication or intervention to assist defection within the previous 24 hours. A bowel movement occurring within 24 hours of an optional assisted method for defecation was not considered to be an SBM. A CSBM was defined as an SBM with the feeling of complete evacuation.
measure: A change in the mean Bristol Stool Form Scale score for stool consistency of spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: For stool consistency, each patient was asked to record their stool consistency according to the Bristol Stool Form Scale, on the following seven points scale. (scored from 1 to 7 for stool types 1 to 7, respectively)
measure: A change in the mean score for the straining of spontaneous bowel movements (SBMs) from the baseline during weeks 1-8 and weeks 13-16
time frame: weeks 1-8, and weeks 13-16
description: For assessment of straining of SBM, each patient was asked to rate his/her score for straining using the following five-point scale: not at all difficulty (0), a little bit difficulty (1), moderately difficulty (2), quite a bit difficulty (3), extremely difficulty (4).
measure: A change in the total and subscale score of the Patient Assessment of Constipation-Symptom (PAC-SYM) questionnaire from baseline at weeks 8 and 16
time frame: week 8 and week 16
description: The PAC-SYM is a 12-item evaluative questionnaire for the chronic constipation, which consists of 4-item abdominal, 3-item rectal, and 5-item stool subscales. Each item score ranges from 0 to 4 in the 2 weeks (14 days) prior to assessment. The, where 0 = symptom absent, 1 = mild,2 = moderate,3 = severe and 4 = very severe. Lower scores indicate a lower symptom burden. Each subscale score will be calculated as the mean of the completed items for that subscale. The total score will be calculated as the mean of all completed items.
measure: A change in the total and subscale scores of the Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires from the baseline at weeks 8 and 16
time frame: week 8 and week 16
description: The PAC-QOL is a 28-item self-reported instrument for assessing the burden of constipation on patients' everyday functioning and well-being in the 2 weeks (14 days) prior to assessment. It is divided into four subscales: physical discomfort (items 1-4), psychosocial discomfort (items 5-12), worries/concerns (items 13-23), and satisfaction (items 24 to 28). Each of the item scores ranges from 0 (not at all) to 4 (extremely), with lower scores indicating a better quality of life. For each visit, individual subscale scores will be calculated as the mean of the completed items for that subscale.
measure: Patients' global assessment of treatment efficacy
time frame: week 8 and week 16
description: each patient was asked to rate his/her efficacy of treatment using the following 7-point self-reporting scale: markedly worse (1), moderately worse (2),slightly worse (3), no change (4), slightly improved (5), moderately improved (6), markedly improved (7).
measure: The proportion of patients using rescue medicine and the mean frequency of rescue medicine use per week during weeks 1-8 and weeks 9-16
time frame: weeks 1-8, and weeks 9-16
description: The proportion of patients using rescue medicine will be compared between groups during weeks 1-8, and weeks 9-16. The mean frequency of using rescue medicine per week during weeks 1-8 equals the total of rescue medicine consumption divided by 8. The mean frequency of using rescue medicine per week during weeks 9-16 equals the total of rescue medicine consumption divided by 8.
measure: Patients'expectation of the acupuncture efficacy
time frame: at baseline
description: Participants will be asked to answer the following questions before the intervention: "Do you think acupuncture will be effective in treating the disease in general?" "Do you think acupuncture will be effective in improving the OIC?" and "which acupuncture modalities do you prefer, EA or SA?" For each question, patients will choose one of the following answers: "unclear/whatever", "EA", or "SA"
measure: The patient blinding assessment
time frame: at week 8
description: Five minutes after the end of any treatment in the eighth week the patients will be asked to answer the following question: "Is traditional EA the acupuncture modality that you have received?".
measure: Incidence of adverse events
time frame: week 1 to week 16
description: All adverse events (AEs) t will be recorded throughout the whole trial in case report form. AEs will be categorized as treatment-related (e.g., broken needle, dizziness, fainting, localized hematoma, localized infection or abscess, or some discomforts after acupuncture) and non-treatment-related. Detailed information regarding AEs and serious adverse events (SAEs)-including the name, onset and end date, intensity, relationship with acupuncture and outcome-will be recorded.
measure: The intensity of cancerous pain evaluation
time frame: at baseline, at weeks 2, 4, 6, 8 and 16.
description: The mean cancerous pain intensity and worst cancerous pain intensity during the preceding week will be evaluated by 11 grades (from "0=no pain" to "10=worst pain (the strongest pain ever experienced)" at baseline, as well as weeks 2, 4, 6, 8 and 16.
measure: The proportion of patients discontinuing the opioid, and those with a ≥30% weekly mean increase or decrease in the dose of opioid from baseline during weeks 1-8 and weeks 9-16
time frame: at week 8 and week 16
description: The proportion of patients discontinuing the opioid, and those with increase/decrease from baseline of ≥30% opioid usage per week will be compared between groups during weeks 1-8, and weeks 9-16
arm group label: Electroacupuncture group
arm group type: Experimental
description: Bilateral ST25,SP14, ST37 will be used in the EA group. For ST25 and SP14, 0.30×50mm or 0.30×75mm needles will be vertically inserted to the muscle layer of the abdominal , where patients will feel sharp pain and acupuncturists will feel resistance from the needle tip. For ST37, 0.30×40 mm needles will be vertically inserted approximately 15 mm deep, followed by three-time manipulation of even lifting and twisting method to elicit the sensation of deqi. Then paired alligator clips of the EA apparatus will be attached to the needle holders of the bilateral ST25, SP14, and ST37. EA stimulation will be retained for 30 minutes with a continuous wave of 10 Hz and current intensity of 0.5 to 4 mA.
arm group label: Sham electroacupuncture group
arm group type: Sham Comparator
description: Bilateral sham ST25, SP14, and ST37 will be used in the SA group. After sterilizing the skin, 0.30×40mm needles will be straightly inserted at the sham points about 2-3mm until they can be fixed on the skin when attached by the alligator clips. No manipulation will be used, and no deqi sensation are elicited for all sham points. The bilateral sham ST25, SP14, and ST37 points will be attached by the same EA apparatus with a continuous wave of 10 Hz and current intensity of 0.1 to 0.2 mA for 30 minutes with only the initial 30 seconds on.
intervention type: Other
intervention name: Electroacupuncture group
description: Bilateral Tianshu (ST25), Fujie (SP14), Shangjuxu (ST37) will be used in the EA group. With the local skin of the patients was routinely sterilized in a prone position in relaxation, acupuncturists will insert needles into the acupuncture points. For ST25 and SP14, 0.30×50mm or 0.30×75mm needles will be vertically inserted to the muscle layer of the abdominal wall, where participants will feel sharp pain and acupuncturists will feel resistance from the needle tip. For ST37, 0.30×40 mm needles will be vertically inserted approximately 15 mm deep, followed by three-time manipulation of even lifting and twisting method to elicit the sensation of deqi. Then paired alligator clips of the EA apparatus will be attached to the needle holders of the bilateral ST25, SP14, and ST37. EA stimulation will be retained for 30 minutes with a continuous wave of 10 Hz and current intensity of 0.5 to 4 mA.
arm group label: Electroacupuncture group
intervention type: Other
intervention name: Sham electroacupuncture group
description: Bilateral sham ST25, SP14, and ST37 will be used in the SA group. After sterilizing the skin, 0.30×40mm needles will be straightly inserted at the sham points about 2-3mm until they can be fixed on the skin when attached by the alligator clips. No manipulation will be used, and no deqi sensation are elicited for all sham points. The bilateral sham ST25, SP14, and ST37 points will be attached by the same EA apparatus with a continuous wave of 10 Hz and current intensity of 0.1 to 0.2 mA for 30 minutes with only the initial 30 seconds on.
arm group label: Sham electroacupuncture group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Zhishun Liu
role: Study Chair
affiliation: China Academy of Chinese Medicine Sciences
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Guang'anmen Hospital of China Academy of Chinese Medical Sciences
investigator full name: Liu Zhishun
investigator title: Principal Investigator
mesh term: Constipation
mesh term: Opioid-Induced Constipation
sharing ipd: No
submitted: August 7, 2022
returned: July 7, 2023
submitted: July 28, 2023