Electroacupuncture in Symptom Management After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Cancer Clinical Trial

Official title:

Electroacupuncture in Symptom Management After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06340906
• Other study ID #: 4573
• Secondary ID: UCI 23-29
• Status: Not yet recruiting
• Phase: N/A
• Start date: May 15, 2024
• Est. completion date: January 30, 2026

Study information

• Verified date: April 2024
• Source: University of California, Irvine
• Contact: Oliver Eng, MD
• Phone: (714) 456-8000
• Email: oeng[@]hs.uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigators are conducting this research study is to evaluate the feasibility (recruitment, compliance, safety, and acceptance) of using electroacupuncture (EA) to manage complex symptoms such as pain, nausea/vomiting, diarrhea, and insomnia in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Additionally, the investigators are aiming to determine the effectiveness of EA in reducing these symptoms, and to examine how EA impacts important biomarkers, or proteins in the blood, that can be used as indicators or signs of these symptoms.

Description:

This is a single-arm, prospective pilot/feasibility study. Patients can be enrolled at any time prior to undergoing surgery. The protocol and interventions are as described in the above schema. Baseline assessments including the above surveys and inflammatory markers will be obtained at the preoperative visit. The same assessments will be performed at approximately 1 month s/p Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Electroacupuncture interventions will be performed between postoperative months 1 to 3; a total of 8 weekly interventions will be performed. A completion assessment will be performed at approximately 6 months s/p Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Our specific aims are as follows:

To examine the feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

To characterize symptoms experienced by patients during recovery from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

To evaluate the utilization of EA in symptom management during recovery from Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

To evaluate levels of biomarkers such as circulating brain-derived neurotrophic factor, pro-inflammatory cytokines (IL-1beta, IL-4, IL-6, IL-8, IL-10, Tumor necrosis factor-alpha), mitochondrial DNA after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy and with utilization of EA.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: January 30, 2026
• Est. primary completion date: November 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with known peritoneal disease who are scheduled to undergo Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

• Age =18 years

• Eastern Cooperative Oncology Group performance status =2

• Patients must have adequate organ and marrow function as defined through laboratory tests

• Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial

• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load

• Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial

• Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better (class 2B is defined as having cardiac enlargement but no history of congestive heart failure)

• Expected survival greater than 9 months

• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients with coexistence of another untreated malignant neoplasm other than basal cell carcinoma of the skin within the last five years

• Sites of metastases other than loco-regional lymph nodes and peritoneum (ex. Visceral metastases such as liver, lungs, bone, brain)

• Patients with uncontrolled intercurrent illness

• Severe needle phobia

• Patients with psychiatric illness/social situations that would limit compliance with study requirements

• Known bleeding disorder (e.g. hemophilia, Von Willebrand's disease, thrombocytopenia)

• Pacemaker or other electronic metal implants

• Epilepsy

• Received acupuncture therapy within the past 3 months prior to study enrollment

• Patients who are breastfeeding, pregnant or are planning get pregnant during the study period.

Related Conditions & MeSH terms

• Cancer
• Fever
• Hyperthermia

Intervention

Other:
• Electroacupuncture
EA at 10 standardized acu-points that were chosen for their therapeutic effects: Zhongwan (CV12), Guanyuan (CV4), Neiguan (PC6), Shenmen (HT7), Hegu (LI4) bilateral, Zusanli (ST36), Sanyinjiao (SP6), Zhaohai (KI6), Taichong (LR3) bilateral, Tian Shu (ST25) bilateral.

Locations

Country	Name	City	State
United States	UCI Health Susan Samueli Integrative Health Institute	Irvine	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Irvine

Country where clinical trial is conducted

United States, 

References & Publications (18)

Bao T, Patil S, Chen C, Zhi IW, Li QS, Piulson L, Mao JJ. Effect of Acupuncture vs Sham Procedure on Chemotherapy-Induced Peripheral Neuropathy Symptoms: A Randomized Clinical Trial. JAMA Netw Open. 2020 Mar 2;3(3):e200681. doi: 10.1001/jamanetworkopen.2020.0681. — View Citation

Bartlett EK, Meise C, Roses RE, Fraker DL, Kelz RR, Karakousis GC. Morbidity and mortality of cytoreduction with intraperitoneal chemotherapy: outcomes from the ACS NSQIP database. Ann Surg Oncol. 2014 May;21(5):1494-500. doi: 10.1245/s10434-013-3223-z. Epub 2013 Aug 29. — View Citation

Chan K, Lui L, Lam Y, Yu K, Lau K, Lai M, Lau W, Tai L, Mak C, Bian Z, Zhong LL. Efficacy and safety of electroacupuncture for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: a single-blinded, randomized, sham-controlled trial. Acupunct Med. 2023 Oct;41(5):268-283. doi: 10.1177/09645284221125421. Epub 2022 Nov 3. — View Citation

Ihemelandu CU, McQuellon R, Shen P, Stewart JH, Votanopoulos K, Levine EA. Predicting postoperative morbidity following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CS+HIPEC) with preoperative FACT-C (Functional Assessment of Cancer Therapy) and patient-rated performance status. Ann Surg Oncol. 2013 Oct;20(11):3519-26. doi: 10.1245/s10434-013-3049-8. Epub 2013 Jun 8. — View Citation

Kaya H, Sezgi C, Tanrikulu AC, Taylan M, Abakay O, Sen HS, Abakay A, Kucukoner M, Kapan M. Prognostic factors influencing survival in 35 patients with malignant peritoneal mesothelioma. Neoplasma. 2014;61(4):433-8. doi: 10.4149/neo_2014_053. — View Citation

Kuchler T, Bestmann B, Rappat S, Henne-Bruns D, Wood-Dauphinee S. Impact of psychotherapeutic support for patients with gastrointestinal cancer undergoing surgery: 10-year survival results of a randomized trial. J Clin Oncol. 2007 Jul 1;25(19):2702-8. doi: 10.1200/JCO.2006.08.2883. Erratum In: J Clin Oncol. 2007 Sep 20;25(27):4328. — View Citation

Low CA, Bovbjerg DH, Ahrendt S, Alhelo S, Choudry H, Holtzman M, Jones HL, Pingpank JF Jr, Ramalingam L, Zeh HJ 3rd, Zureikat AH, Bartlett DL. Depressive Symptoms in Patients Scheduled for Hyperthermic Intraperitoneal Chemotherapy With Cytoreductive Surgery: Prospective Associations With Morbidity and Mortality. J Clin Oncol. 2016 Apr 10;34(11):1217-22. doi: 10.1200/JCO.2015.62.9683. Epub 2016 Feb 22. — View Citation

Lutgendorf SK, Andersen BL. Biobehavioral approaches to cancer progression and survival: Mechanisms and interventions. Am Psychol. 2015 Feb-Mar;70(2):186-97. doi: 10.1037/a0035730. — View Citation

Moaven O, Votanopoulos KI, Shen P, Mansfield P, Bartlett DL, Russell G, McQuellon R, Stewart JH, Levine EA. Health-Related Quality of Life After Cytoreductive Surgery/HIPEC for Mucinous Appendiceal Cancer: Results of a Multicenter Randomized Trial Comparing Oxaliplatin and Mitomycin. Ann Surg Oncol. 2020 Mar;27(3):772-780. doi: 10.1245/s10434-019-08064-6. Epub 2019 Nov 12. — View Citation

Morgan RB, Tun S, Eng OS: Quality of life after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a narrative review [Internet]. Dig Med Res 3:53-53, 2020[cited 2023 Jan 4] Available from: https://dmr.amegroups.com/article/view/6846/html

Napadow V, Makris N, Liu J, Kettner NW, Kwong KK, Hui KK. Effects of electroacupuncture versus manual acupuncture on the human brain as measured by fMRI. Hum Brain Mapp. 2005 Mar;24(3):193-205. doi: 10.1002/hbm.20081. — View Citation

Osann K, Wilford J, Wenzel L, Hsieh S, Tucker JA, Wahi A, Monk BJ, Nelson EL. Relationship between social support, quality of life, and Th2 cytokines in a biobehavioral cancer survivorship trial. Support Care Cancer. 2019 Sep;27(9):3301-3310. doi: 10.1007/s00520-018-4617-z. Epub 2019 Jan 5. — View Citation

Quenet F, Elias D, Roca L, et al: A UNICANCER phase III trial of hyperthermic intra-peritoneal chemotherapy (HIPEC) for colorectal peritoneal carcinomatosis (PC): PRODIGE 7. [Internet]. J Clin Oncol 36:LBA3503-LBA3503, 2018Available from: https://doi.org/10.1200/JCO.2018.36.18_suppl.LBA3503

Stearns AT, Malcomson L, Punnett G, Abudeeb H, Aziz O, Selvasekar CR, Fulford PE, Wilson MS, Renehan AG, O'Dwyer ST. Long-term Quality of Life After Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei: A Prospective Longitudinal Study. Ann Surg Oncol. 2018 Apr;25(4):965-973. doi: 10.1245/s10434-017-6326-0. Epub 2018 Jan 8. — View Citation

Verwaal VJ, van Ruth S, de Bree E, van Sloothen GW, van Tinteren H, Boot H, Zoetmulder FA. Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol. 2003 Oct 15;21(20):3737-43. doi: 10.1200/JCO.2003.04.187. — View Citation

Wang Y, Yang JW, Yan SY, Lu Y, Han JG, Pei W, Zhao JJ, Li ZK, Zhou H, Yang NN, Wang LQ, Yang YC, Liu CZ. Electroacupuncture vs Sham Electroacupuncture in the Treatment of Postoperative Ileus After Laparoscopic Surgery for Colorectal Cancer: A Multicenter, Randomized Clinical Trial. JAMA Surg. 2023 Jan 1;158(1):20-27. doi: 10.1001/jamasurg.2022.5674. — View Citation

Witt CM, Balneaves LG, Cardoso MJ, Cohen L, Greenlee H, Johnstone P, Kucuk O, Mailman J, Mao JJ. A Comprehensive Definition for Integrative Oncology. J Natl Cancer Inst Monogr. 2017 Nov 1;2017(52). doi: 10.1093/jncimonographs/lgx012. — View Citation

Yan TD, Deraco M, Baratti D, Kusamura S, Elias D, Glehen O, Gilly FN, Levine EA, Shen P, Mohamed F, Moran BJ, Morris DL, Chua TC, Piso P, Sugarbaker PH. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for malignant peritoneal mesothelioma: multi-institutional experience. J Clin Oncol. 2009 Dec 20;27(36):6237-42. doi: 10.1200/JCO.2009.23.9640. Epub 2009 Nov 16. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Biomarkers - Plasma (pg/mL)	To evaluate levels of biomarkers such as circulating brain-derived neurotrophic factor, pro-inflammatory cytokines (IL-1beta, IL-4, IL-6, IL-8, IL-10, Tumor necrosis factor-alpha), mitochondrial DNA after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy and with utilization of EA.	Blood biomarkers will be measured at baseline, 1 month post-surgery, and 6 months post-surgery.
Other	Vital Signs - Blood Pressure (mmHg)	The systolic and diastolic blood pressure of each patient will be measured prior to surgery as part of the screening process for eligibility for participation. This is to ensure the patient's stability in both undergoing the surgery and EA.	Blood pressure will only be measured at baseline.
Other	Vital Signs - Heart Rate (bpm)	The heart rate of each patient will be measured prior to surgery as part of the screening process for eligibility for participation. This is to ensure the patient's stability in both undergoing the surgery and EA.	Heart rate will only be measured at baseline.
Other	Vital Signs - Body Temperature (C)	The body temperature of each patient will be measured prior to surgery as part of the screening process for eligibility for participation. This is to ensure the patient's stability in both undergoing the surgery and EA.	Body temperature will only be measured at baseline.
Other	Vital Signs - Respiration Rate (breaths/minute)	The respiration rate of each patient will be measured prior to surgery as part of the screening process for eligibility for participation. This is to ensure the patient's stability in both undergoing the surgery and EA.	Respiration rate will only be measured at baseline.
Other	Vital Signs - Oxygen Saturation Rate (%)	The oxygen saturation rate of each patient will be measured prior to surgery as part of the screening process for eligibility for participation. This is to ensure the patient's stability in both undergoing the surgery and EA.	Oxygen saturation rate will only be measured at baseline.
Other	Height (feet and inches)	The participant's height will be measured prior to surgery to ensure anesthesia dosage required for the procedure is accurate to prevent any associated risk of complications during the surgery.	Height will only be measured at baseline.
Other	Weight (kg)	The participant's weight will be measured prior to surgery to ensure anesthesia dosage required for the procedure is accurate to prevent any associated risk of complications during the surgery.	Weight will only be measured at baseline.
Other	Incidence of Treatment-Emergent Adverse Events - Safety Monitoring	Participants will be monitored for adverse events such as bruising, pain or discomfort, bleeding and possible infections. Severity are graded according to the Common Terminology Criteria for Adverse Events V5.	Through study completion; Approximately 1.5 years
Other	Biomarkers - Plasma BDNF (pg/ml)	Plasma brain-derived neurotropic factor (BDNF) levels at each time point, and changes from baseline.	Baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Other	Biomarkers - Plasma cytokines (IL-1ß, IL-4, IL-6, IL-8, IL-10, TNF-alpha, pg/mL)	Plasma cytokine levels at each time point, and changes from baseline.	Baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Other	Mitochondrial DNA content	Mitochondrial DNA (mtDNA) content at each time point, and changes from baseline	Baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Number of Patients Recruited	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through the number of participants recruited (% of target recruitment).	Through study completion; approximately 1.5 years.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Patient Recruitment Rate	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through assessing the number of patients recruited per month.	Through study completion; approximately 1.5 years.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Reasons for Abstaining from Participation	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through assessing the reasons both active and potential participants declined participation.	Through study completion; approximately 1.5 years.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Recruitment Duration	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through the time spent on recruitment, in minutes.	Through study completion; approximately 1.5 years.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Number of Completed Electroacupuncture Sessions	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through patient adherence to the study procedures through assessing the number of electroacupuncture sessions successfully completed in total.	Through study completion; approximately 1.5 years.
Primary	Feasibility in utilizing an EA for patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy - Proportion of Completed Electroacupuncture Sessions	The feasibility of utilizing an EA protocol in patients who have undergone Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy will be assessed through patient adherence to the study procedures through assessing the proportion of participants completing all the scheduled electroacupuncture sessions.	Through study completion; approximately 1.5 years.
Secondary	Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Symptoms - EORTC QLQ-C30	The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) is a validated questionnaire developed to assess cancer patients' health-related quality of life. It incorporates 5 functional scales (cognitive, emotional, physical, role, and social), symptom scales (e.g. pain, fatigue, insomnia), and a global health scale. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale. Higher scores represent a better global health status and better degree of functioning while lower symptom scores indicate less severe symptoms.; In addition to this questionnaire, patients' clinical notes will be reviewed to better characterize the respective symptoms.	All the mean scores will be compared at baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Secondary	Efficacy of EA in managing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Symptoms - EORTC QLQ-C30	The European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-30) is a validated questionnaire developed to assess cancer patients' health-related quality of life. It incorporates 5 functional scales (cognitive, emotional, physical, role, and social), symptom scales (e.g. pain, fatigue, insomnia), and a global health scale. Most questions used 4-point scale (1 'Not at All' to 4 'Very Much'); 2 questions used 7-point scale (1 'Very Poor' to 7 'Excellent'). Scores are averaged, and transformed to 0-100 scale. Higher scores represent a better global health status and better degree of functioning while lower symptom scores indicate less severe symptoms.	All the mean scores will be compared at baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Secondary	Efficacy of EA in managing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Symptoms - FACT-Cog version 3	All subjects will complete the FACT-Cog version 3 questionnaire to assess self-perceived subjective cognitive function. FACT-Cog is a validated questionnaire containing 33 items in the domains of concentration, functional interference, mental acuity, memory, multitasking and verbal fluency. Total score is calculated by summing scores from all the items and ranges from 0-148, and higher scores represent better subjective cognitive functioning.	All the mean scores will be compared at baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.
Secondary	Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Symptoms - FACT-Cog version 3	All subjects will complete the FACT-Cog version 3 questionnaire to assess self-perceived subjective cognitive function. FACT-Cog is a validated questionnaire containing 33 items in the domains of concentration, functional interference, mental acuity, memory, multitasking and verbal fluency. Total score is calculated by summing scores from all the items and ranges from 0-148, and higher scores represent better subjective cognitive functioning.; This questionnaire will be utilized to better characterize the effects Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy on cognitive function. of In addition to this questionnaire, patients' clinical notes will be reviewed for more robust characterization of the symptoms.	All the mean scores will be compared at baseline (before surgery), 1 month post-surgery, and 6 months post-surgery.