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Effect of Electroacupuncture for the Treatment of Opioid-induced Constipation in Patients With Cancer

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ClinicalTrials.gov Identifier: NCT03797586
Recruitment Status : Not yet recruiting
First Posted : January 9, 2019
Last Update Posted : January 9, 2019
Sponsor:
Information provided by (Responsible Party):
Liu Zhishun, Guang'anmen Hospital of China Academy of Chinese Medical Sciences

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Opioid-induced Constipation in Patients With Cancer Other: Electroacupuncture group Other: Sham electroacupuncture group Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 192 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of Electroacupuncture for the Treatment of Opioid-induced Constipation in Patients With Cancer: Study Protocol for an Upcoming Multicenter Randomized Controlled Trial
Estimated Study Start Date : March 1, 2019
Estimated Primary Completion Date : February 28, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Constipation

Arm Intervention/treatment
Experimental: Electroacupuncture group
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 . For ST37, 0.30×40mm needles will be vertically inserted approximately 15 mm. For all the acupuncture points, needle insertion will be followed by manipulation with an even lifting and twisting method three times 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.
Other: Electroacupuncture group
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, 0.30×40mm needles will be vertically inserted approximately 15 mm. For all the acupuncture points, needle insertion will be followed by manipulation with an even lifting and twisting method three times 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.

Sham Comparator: Sham electroacupuncture group
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 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.
Other: Sham electroacupuncture group
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 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.




Primary Outcome Measures :
  1. The proportion of responders [ Time Frame: weeks 1-8 ]
    A responder is defined as a patient having at least three spontaneous bowel movements(SBMs) per week with an increase from baseline of at least one SBM per week for at least 6 weeks of the 8-week treatment period.


Secondary Outcome Measures :
  1. Change in the mean frequency of spontaneous bowel movements(SBMs) per week from baseline [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  2. The proportion of patients with ≥3 spontaneous bowel movements(SBMs) per week [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  3. The proportion of patients with increase from baseline of ≥1 spontaneous bowel movements(SBMs) per week [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  4. Change in the mean frequency of complete spontaneous bowel movements(CSBMs) per week from baseline [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  5. The proportion of patients with ≥3complete spontaneous bowel movements(CSBMs) per week [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  6. The proportion of patients with increase from baseline of ≥1 complete spontaneous bowel movements(CSBMs) per week [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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.

  7. Change in mean Bristol Stool Form Scale score for stool consistency of spontaneous bowel movements(SBMs) [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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)

  8. Change in mean score for straining of spontaneous bowel movements(SBMs) [ Time Frame: weeks 1-8, and weeks 13-16 ]
    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).

  9. Change in Patient Assessment of Constipation-Symptom (PAC-SYM) questionnaires total score and subscale scores [ Time Frame: week 8 and week 16 ]
    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.

  10. Change in Patient Assessment of Constipation-Quality of Life (PAC-QOL) questionnaires total score and subscale scores [ Time Frame: week 8 and week 16 ]
    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.

  11. Patients'global assessment of treatment efficacy [ Time Frame: week 8 and week 16 ]
    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).

  12. The proportion of patients using rescue medicine and mean frequency of using rescue medicine per week [ Time Frame: weeks 1-8, and weeks 9-16 ]
    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.

  13. The proportion of patients with increase/decrease from baseline of ≥30% opioid usage per week during weeks 1-8, and weeks 13-16 [ Time Frame: at week 8 and week 16 ]
    The proportion of patients with increase/decrease from baseline of ≥30% opioid usage per week will be compared between groups during weeks 1-8, and weeks 9-16.


Other Outcome Measures:
  1. Patients'expectation of the acupuncture efficacy [ Time Frame: at baseline ]
    Patients'expectation of the acupuncture efficacy will be recorded at baseline. Participants will be asked to answer the following questions before the intervention: "Do you think acupuncture will be effective for treating the disease?" "Do you think acupuncture will be effective for improving the OIC?" and "which acupuncture modalities do you prefer, EA or SA?" For each question, participants will choose one of the following answers: "unclear/whatever", "Yes", or "No".

  2. The proportion of patients with successful blinding [ Time Frame: at week 8 ]
    Successful blinding was defined as participants who are unclear about which treatment they had taken. Participants will be informed that they will receive each of the two acupuncture modalities: the traditional EA with a deep insertion or the SA with a shallow insertion. 5 minutes after the end of any treatment of week 8, they will be asked to answer the following question: "Is traditional EA the acupuncture modality you have received? Unclear, Yes or No".

  3. Incidence of adverse events [ Time Frame: week 1 to week 16 ]
    All adverse events (AEs) through the whole trial will be reported in case report form. AEs will be categorized as treatment-related (e.g., broken needle, dizziness, fainting, intolerable pain (Visual Analogue Scale≥8, 0[no pain] to 10[worst imaginable pain]), localized hematoma, localized infection or abscess, or some discomforts after acupuncture) and non-treatment-related within 24 hours after their occurrence. Detailed information on AEs and serious adverse events (SAEs)—including the name, onset and end date, intensity, relationship with acupuncture and outcome—will be recorded.

  4. The intensity of cancerous pain evaluation [ Time Frame: at baseline, at weeks 2, 4, 6, 8 and 16. ]
    The mean cancerous pain intensity and worst cancerous pain intensity during the preceding 1 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.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Cancer patients who conformed to all the following conditions will be further screened for eligibility:

  1. Patients who are between the ages of ≥18 and ≤75 years;
  2. Patients whose cancer condition is stable and life expectancy is more than 6 months;
  3. Patients who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
  4. Patients who meet the diagnostic criteria for OIC irrespective of a history of chronic functional constipation. For patient with a history of chronic functional constipation, he/she must have worsening symptoms of constipation (≥1 weekly spontaneous bowel movement (SBM) reduction over the last week) when initiating, changing, or increasing opioid therapy. Meanwhile, specialist physicians will determine the constipation is not attributed to some other secondary causes except the use of opioids;
  5. Patients who have been receiving a stable maintenance opioid regimen consisting of a total daily dose of 30mg to 1000mg oral morphine equivalents for at least 2 weeks prior to screening for cancer pain, and who are anticipated to maintain the regularly stable dose for at least 18 weeks;
  6. Patients whose SBM frequency during baseline is 2 times or less;
  7. Patients who are capable of oral intake of drugs, food and beverages;
  8. Patients who have not participant in the clinical study with or without respect to acupuncture for constipation within 2 weeks prior to screening;
  9. Provision of written informed consent before inclusion.

Exclusion Criteria:

Participants who fulfill any of the following criteria will be excluded:

  1. Diagnosis of primary or secondary gastrointestinal cancer, peritoneal tumor, or skin cancer;
  2. a history of gastrointestinal tract operation, abdominal operation, or abdominal adhesion within 1 month prior to screening; history of intestinal obstruction within 1 year;
  3. patients with ascites; inflammatory bowel disease; or active diverticular disease; or mechanical gastrointestinal obstruction; or severe hemorrhoid; or anal fissure; or artificial rectum or anus; or other significant structural abnormalities of the gastrointestinal tract (such as scarring)
  4. patients with intraperitoneal catheter, or use of feeding tube to maintain vital signs;
  5. patients with bowel dysfunction and pelvic disorder which are considered to have obvious effects on intestinal transport of feces (such as uterine prolapsed or rectal prolapsed ≥degree 2, uterine fibroids(located in the posterior of the uterus with a diameter r≥ 5cm ) affecting bowel movement);
  6. Patients who were treated with new cancer chemotherapy, which had never been administered in the past, within 14 days before screening, or who are scheduled to receive such therapy during the study;
  7. Patients who received radiotherapy within 28 days before screening, or who are scheduled to receive such therapy during the study;
  8. Patients who underwent surgery or intervention which is considered to have obvious effects on the gastrointestinal functions within 28 days before screening or who are scheduled to receive surgery or intervention which is considered to have obvious effects on the gastrointestinal functions during the study, or patients who are scheduled to receive surgery or intervention which will be anticipated to prevent the patients from completing the trial;
  9. Uncontrolled hyperthyroidism, severe hypertension, heart disease, systematic infection; or blood coagulation disorders (hypercoagulation status or hemorrhagic tendency);
  10. Patients who consumed >4 opioid doses for breakthrough pain per day for more than 3 days during the baseline, or if their maintenance opioid dosing regimen was modified during this same period;
  11. Severe background pain (eg, typical average daily pain intensity rating of 7 to 10 on an numerical rating scales (NRS; 0 [no pain] to 10 [the worst pain possible]) after the utility of routine dose and frequency of opioids) refractory to opioid therapy;
  12. Patients who have a history of opioid discontinuation due to severe adverse events; or are suspected to discontinue opioid due to a potential risk of adverse events;
  13. Patients who received opioid receptor antagonist or agonist within 1 month before screening, or who are scheduled to receive such therapy during the study;
  14. Patients who have a history of nerve block or neurolysis;
  15. Patients with severe cognitive impairment, aphasia, or a psychiatric disorder; or abdominal aortic aneurysm; or hepatomegaly; or splenomegaly;
  16. Other patients who will be considered ineligible for the study by the investigator on the basis of concomitant therapy and medical findings;

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03797586


Contacts
Contact: weiming wang 01088001241 wangweiming1a1@163.com
Contact: zhishun liu 01088002331 zhishunliu@aliyun.com

Sponsors and Collaborators
Guang'anmen Hospital of China Academy of Chinese Medical Sciences
Investigators
Principal Investigator: Zhishun Liu China Academy of Chinese Medicine Sciences

Responsible Party: Liu Zhishun, Principal Investigator, Guang'anmen Hospital of China Academy of Chinese Medical Sciences
ClinicalTrials.gov Identifier: NCT03797586     History of Changes
Other Study ID Numbers: 2018-164-KY-01
First Posted: January 9, 2019    Key Record Dates
Last Update Posted: January 9, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Liu Zhishun, Guang'anmen Hospital of China Academy of Chinese Medical Sciences:
electroacupuncture;opioid-induced constipation ,cancer

Additional relevant MeSH terms:
Constipation
Signs and Symptoms, Digestive
Signs and Symptoms
Analgesics, Opioid
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents