Electroacupuncture for the Management of Symptom Clusters in Cancer Patients and Survivors

Cancer Clinical Trial

— EAST  

Official title:

Electroacupuncture for the Management of Symptom Clusters in Cancer Patients and Survivors (EAST): A Feasibility Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05283577
• Other study ID #: 20216732
• Status: Recruiting
• Phase: N/A
• Start date: April 15, 2022
• Est. completion date: December 2024

Study information

• Verified date: May 2024
• Source: University of California, Irvine
• Contact: Alexandre Chan, PharmD
• Phone: 1-949-824-8896
• Email: a.chan[@]uci.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a sham-controlled, patient and assessor-blinded pilot trial to evaluate the feasibility of administering EA as an intervention for symptom clusters in cancer patients and survivors, and to evaluate the degree that EA could reduce symptom clusters and the possible underlying mechanisms through examining its influence on biomarkers that are linked with the symptoms.

Participants will be randomized to either the treatment arm (those who will receive EA) or the control arm (those who will receive sham-EA). The treatment period for both groups will be 10 weeks. There will be one study visit a week over the course of the 10-week treatment period, for a total of 10 study treatment visits. Participants in the treatment arm will receive EA at 13 standardized acu-points that have been chosen for their therapeutic effects. Participants in the control arm will receive electrical stimulation at non-disease acu-points. There will be four data collection time points for each participant: (1) baseline, (2) mid-treatment (5 weeks from baseline), (3) end of treatment (10 weeks from baseline), and (4) 4 weeks after end of treatment (14 weeks from baseline). At each of these timepoints, 10mL of peripheral blood will be collected for a biomarker analysis and participants will be asked to complete 4 questionnaires and a computerized cognitive test to evaluate their cognitive function, fatigue level, insomnia, psychological distress, and quality of life. An optional neuroimaging procedure will be available to all eligible participants. In total, study participation will last for 14 weeks.

Description:

The purpose of this study is to investigate the efficacy, safety, and feasibility of offering electroacupuncture as an intervention to improve cancer-related symptoms (cognitive impairment, fatigue, psychological distress and insomnia) and quality of life among cancer patients and survivors receiving care at UCI Health. In addition, changes in biomarkers (plasma BDNF, pro-inflammatory cytokines and mitochondrial DNA) known to be associated with cancer-related symptoms. We hypothesize that EA is an effective, safe, and feasible intervention for cancer patients and survivors.

Our specific aims are as follows:

• To compare the efficacy of EA versus sham-EA control in reducing cognitive toxicity, fatigue, psychological distress, insomnia, and to improve quality of life.

• To evaluate the impact of EA versus sham-EA control on biomarkers, including circulating BDNF, pro-inflammatory cytokines (IL-1β, IL-4, IL-6, IL-8, IL-10, TNF-alpha), mitochondrial DNA (oxidative stress indicator).

• To compare the reduction of structural (brain gray matter) and functional connectivity at the prefrontal, medial temporal, and parietal brain regions pre- and post-EA treatment.

• To assess the safety and feasibility of administering EA to manage symptom clusters in cancer patients and survivors.

• As the UCI MINDS C2C registry (UCI IRB Approval #: HS# 2015-2494) will be leveraged to recruit some patients, we will quantify the characteristics associated with non-response to our study advertisement among C2C registrants using C2C-collected data.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 88
• Est. completion date: December 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Patients diagnosed with cancer that have received anti-cancer treatment

• 16 years of age or older

• Life expectancy = 6 months

• Complaints of one or more of the following symptoms: memory impairment/attention deficit, fatigue, insomnia, depression, or anxiety over the past 7 days

Exclusion Criteria:

• Presence of metastasis

• Severe needle phobia

• Severe psychiatric or medical disorders which would affect cognitive assessments

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

• Has pacemaker or other electronic metal implants

• Epilepsy

• Already receiving acupuncture therapy or received acupuncture treatment in the past 3 months.

• Breastfeeding, pregnant or are planning get pregnant during the study period

Additional exclusion criteria for optional neuroimaging procedure:

• Has any contraindications to fMRI including metal fragments/implants in the body, sever claustrophobia, and non-removable metal orthodontic braces, metallic retainers and oral wires.

Related Conditions & MeSH terms

• Cancer
• Syndrome

Intervention

Other:
• Electroacupuncture
EA at 13 standardized acu-points that were chosen for their therapeutic effects: Shenting (GV24), Baihui (DU20), Sinshencong (EX-HN1), Zhongwan (CV12), Guanyuan (CV4), Neiguan (PC6) bilateral, Shenmen (HT7) bilateral, Zusanli (ST36) bilateral, Sanyinjiao (SP6) bilateral, Taixi (KI3) bilateral, Zhaohai (KI6) bilateral, Hegu (LI4) bilateral, Taichong (LIV3) bilateral
• Sham-Electroacupuncture
Non-disease related points with electrical stimulation: Pianli (LI6) bilateral, Wenliu (LI7) bilateral, Fuyang (BL59) bilateral, Kunlun (BL60) bilateral, Sanyangluo (TE8), Sidu (TE9) bilateral, Daheng (SP15) 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 (9)

Cheung YT, Ng T, Shwe M, Ho HK, Foo KM, Cham MT, Lee JA, Fan G, Tan YP, Yong WS, Madhukumar P, Loo SK, Ang SF, Wong M, Chay WY, Ooi WS, Dent RA, Yap YS, Ng R, Chan A. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study. Ann Oncol. 2015 Jul;26(7):1446-51. doi: 10.1093/annonc/mdv206. Epub 2015 Apr 28. — View Citation

Cheung YT, Shwe M, Chui WK, Chay WY, Ang SF, Dent RA, Yap YS, Lo SK, Ng RC, Chan A. Effects of chemotherapy and psychosocial distress on perceived cognitive disturbances in Asian breast cancer patients. Ann Pharmacother. 2012 Dec;46(12):1645-55. doi: 10.1345/aph.1R408. Epub 2012 Dec 18. — View Citation

Janelsins MC, Heckler CE, Peppone LJ, Kamen C, Mustian KM, Mohile SG, Magnuson A, Kleckner IR, Guido JJ, Young KL, Conlin AK, Weiselberg LR, Mitchell JW, Ambrosone CA, Ahles TA, Morrow GR. Cognitive Complaints in Survivors of Breast Cancer After Chemotherapy Compared With Age-Matched Controls: An Analysis From a Nationwide, Multicenter, Prospective Longitudinal Study. J Clin Oncol. 2017 Feb 10;35(5):506-514. doi: 10.1200/JCO.2016.68.5826. Epub 2016 Dec 28. — View Citation

Liou KT, Root JC, Garland SN, Green J, Li Y, Li QS, Kantoff PW, Ahles TA, Mao JJ. Effects of acupuncture versus cognitive behavioral therapy on cognitive function in cancer survivors with insomnia: A secondary analysis of a randomized clinical trial. Cancer. 2020 Jul 1;126(13):3042-3052. doi: 10.1002/cncr.32847. Epub 2020 Apr 22. — View Citation

Ng T, Dorajoo SR, Cheung YT, Lam YC, Yeo HL, Shwe M, Gan YX, Foo KM, Loh WK, Koo SL, Jain A, Lee GE, Dent R, Yap YS, Ng R, Chan A. Distinct and heterogeneous trajectories of self-perceived cognitive impairment among Asian breast cancer survivors. Psychooncology. 2018 Apr;27(4):1185-1192. doi: 10.1002/pon.4635. Epub 2018 Feb 1. — View Citation

Toh YL, Tan CJ, Yeo AHL, Shwe M, Ho HK, Gan YX, Foo KM, Chu P, Olson K, Chan A. Association of plasma leptin, pro-inflammatory adipokines and cancer-related fatigue in early-stage breast cancer patients: A prospective cohort study. J Cell Mol Med. 2019 Jun;23(6):4281-4289. doi: 10.1111/jcmm.14319. Epub 2019 Apr 23. — View Citation

Tong T, Pei C, Chen J, Lv Q, Zhang F, Cheng Z. Efficacy of Acupuncture Therapy for Chemotherapy-Related Cognitive Impairment in Breast Cancer Patients. Med Sci Monit. 2018 May 8;24:2919-2927. doi: 10.12659/MSM.909712. — View Citation

Zeng Y, Cheng ASK, Song T, Sheng X, Wang S, Xie J, Chan CCH. Effects of Acupuncture on Cancer-Related Cognitive Impairment in Chinese Gynecological Cancer Patients: A Pilot Cohort Study. Integr Cancer Ther. 2018 Sep;17(3):737-746. doi: 10.1177/1534735418777109. Epub 2018 May 26. — View Citation

Zhang ZJ, Man SC, Yam LL, Yiu CY, Leung RC, Qin ZS, Chan KS, Lee VHF, Kwong A, Yeung WF, So WKW, Ho LM, Dong YY. Electroacupuncture trigeminal nerve stimulation plus body acupuncture for chemotherapy-induced cognitive impairment in breast cancer patients: An assessor-participant blinded, randomized controlled trial. Brain Behav Immun. 2020 Aug;88:88-96. doi: 10.1016/j.bbi.2020.04.035. Epub 2020 Apr 16. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Subjective Cognitive Function (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 before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Objective Cognitive Function (CANTAB®,)	All subjects will complete Cambridge Neuropsychological Test Automated Battery (CANTAB®), to assess objective cognitive functions. CANTAB® is a computerized cognitive testing software to assess various cognitive domains. Both subjective and objective assessments are recommended by the International Cognition and Cancer Task Force (ICCTF).	All the mean scores will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Fatigue (MFSI-SF)	Multidimensional Fatigue Symptom Inventory- Short Form (MFSI-SF) is a validated questionnaire that comprises of 30 items and contains 5 subscales, each with 6 items: general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigor. The total score is obtained by subtracting the vigour subscale from the sum of all the dimensions (total score range from 24 to 96), with a higher score indicating higher fatigue level.	All the mean scores will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Psychological Distress and Insomnia (RSCL)	The Rotterdam Symptom Checklist (RSCL) will be used to measure the psychological symptoms (anxiety and depression) and insomnia. Psychological distress is indicated by a score of >16 in the psychological domain (range 7 to 28). Insomnia is measured by a single item in the checklist (not at all, a little, quite a bit, very much).	All the mean scores will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Quality of Life (EORTC QLQ-30)	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 before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Quality of Life (EQ-5D-5L)	EQ-5D comprises a visual analog scale of general health status ranging from 0 (worst imaginable) to 100 (best imaginable) and a descriptive system based on five dimensions of health status: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ-5D descriptive index responses were mapped into a single dimension health utility index (UI) ranging from death (0) to full health (1), with health states worse than death being possible (<0), by using utility weights for the US population.	All the mean scores will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The mean score changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	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, an average of 14 weeks per participant.
Secondary	Biomarkers - Plasma BDNF (pg/ml)	Plasma brain-derived neurotropic factor (BDNF) levels at each time point, and changes from baseline	BDNF levels will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	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	Cytokine levels will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Biomarkers - Mitochondrial DNA content	Mitochondrial DNA (mtDNA) content at each time point, and changes from baseline	mtDNA content will be compared before acupuncuture and 5, 10 and 14 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 5, 10 and 14 weeks after baseline.
Secondary	Biomarkers - Gray matter volume	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - White matter volume	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - Mean diffusivity	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - Fractional anisotropy	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - Radial diffusivities	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - Axial diffusivities	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Biomarkers - Resting state functional connectivities	Neuroimaging scans (rsfMRI, FLAIR, diffusion weighed, T1-weighted and T2-weighted sequences)	Neuroimaging measures will be compared before acupuncuture and 10 weeks after baseline for EA and sham-EA control groups. The changes will also be compared between the EA and sham-EA control groups at 10 weeks after baseline.
Secondary	Feasibility - Recruitment (number of participants recruited)	The number of participants recruited (% of target recruitment)	Through study completion, approximately 2 years.
Secondary	Feasibility - Recruitment (rate of recruitment)	Number of patients recruited per month	Through study completion, approximately 2 years.
Secondary	Feasibility - Recruitment (reasons for declining participation)	Reasons for declining participation will be documented.	Through study completion, approximately 2 years.
Secondary	Feasibility - Recruitment (time spent on recruitment)	Time spent on recruitment, in minutes, wil be documented to assess recruitment productivity.	Through study completion, approximately 2 years.
Secondary	Feasibility - Compliance (number of acupuncture sessions successfully completed)	Number of acupuncture sessions successfully completed in total	Through study completion, approximately 2 years.
Secondary	Feasibility - Compliance (proportion of participants completing the scheduled acupuncture sessions)	Proportion of participants completing all the scheduled acupuncture sessions	Through study completion, approximately 2 years.
Secondary	Feasibility - Acceptability	Study participants will complete a questionnaire evaluating their perceptions towards the EA treatment at the end of treatment.	Upon completion of treatment, at 10 weeks from baseline.
Secondary	Feasibility - Satisfaction	Participants will be asked if they are satisfied and benefited from the treatment, and whether they would consider undergoing treatment again outside of a trial setting.	Upon completion of treatment, at 10 weeks from baseline.
Secondary	Feasibility - Blinding assessment	Participants will be asked whether they believe that they have received EA or sham-EA at the end of treatment.	Upon completion of treatment, at 10 weeks from baseline.