Acupuncture Prevents Chemobrain in Breast Cancer Patients

May 17, 2019 updated by: Prof. Zhang Zhang-Jin, The University of Hong Kong

An Assessor-Blinded, Randomised Controlled Trial of Acupuncture to Prevent Chemobrain in Breast Cancer Patients

Chemobrain is an expression used to describe a cluster of chemotherapy-induced cognitive impairment symptoms, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients experienced acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors even display as high as 50%-75% prevalence of post-treatment cognitive impairment. Chemobrain has become an apparent quality-of-life issue for cancer survivors and will be encountered more frequently with the rise of the number of cancer survivors. There are no effective interventions available for preventing and treating chemobrain.

Acupuncture is beneficial in reducing various side effects of anti-cancer treatment. It also shows the efficacy in improving mild cognitive impairment and other dementia disorders; facilitates the recovery of pathological microstructural changes of the brain. These results have led to the hypothesis that acupuncture is effective in preventing chemobrain and this preventive effect may be associated with the protection against cytokine production, epigenetic modification and microstructural changes of the brain.

To test this hypothesis, an assessor-blinded, randomised controlled trial will be conducted to determine if a combination of DCEAS and body acupuncture could reduce the incidence and symptoms of chemobrain in breast cancer patients under chemotherapy compared to least acupuncture stimulation (LAS) as controls.

A total of 168 breast cancer patients who are ready for chemotherapy will be randomly assigned to comprehensive acupuncture intervention (combined DCEAS and body acupuncture regimen + chemotherapy) (CAI) (n = 84) for 2 sessions per week for 8 weeks or least acupuncture stimulation (LAS) (minimal acupuncture + chemotherapy) (n = 84). All patients receive the standard chemotherapy of breast cancer. Treatment outcomes on cognitive performance, fatigue and the depression will be assessed.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although the development of various chemotherapeutic drugs has greatly improved clinical outcomes and survival rate of cancer patients, it also causes various adverse side effects. Chemotherapy-induced cognitive impairment, often referred to as chemobrain, has drawn increasing attention due to the rise in the number of cancer survivors over the past decade. Numerous studies have shown that chemotherapy can cause acute and long-term post-treatment cognitive impairment, including problems with visual and verbal memory, forgetfulness, difficulty in learning, attention, concentration and coordination of multitasking and organization. Over 75% cancer patients reported to experience acute cognitive symptoms during chemotherapy and 17%-34% of them have long-term post-treatment cognitive deficits which can persist up to 10 years. Breast cancer survivors may display higher prevalence of post-treatment cognitive impairment. The severity of reported chemobrain symptoms is variable, from subtle to more severe. Chemobrain has become an apparent quality-of-life issue for survivors and will be encountered more frequency in the future. However, there are no effective interventions available to prevent and treat chemobrain, although some pharmacological, antioxidant and various cognitive approaches have been tested.

It is believed that chemobrain is a consequence of brain neuronal injury induced by systemically administered chemotherapeutic agents via direct and indirect mechanisms, resulting in the suppression of neuronal cell proliferation, epigenetic modification and microstructural changes of the brain. These pathological circumstances are largely developed from alternations in cytokine milieu. While physical and psychological stressors that cancer patients experienced after diagnosis, chemotherapy and long-term follow-up have been shown to increase circulating cytokine levels and increased cytokine levels are associated with cognitive decline in cancer patients, the administration of chemotherapy also results in cytokine production at peripheral and central levels as the medications induce tumor cell death and collateral tissue injury. Patients undergoing chemotherapy have been found to display significant increases in multiple cytokines.

A large body of evidence well confirms that acupuncture is effective in reducing anti-cancer treatment-caused side effects, including pain, nausea, hot flashes, fatigue, xerostomia, anxiety, depression and sleep disturbance. Numerous studies further have shown the effectiveness of acupuncture therapy in improving cognitive function of patients with mild cognitive impairment (MCI) and various dementia. The reduced severity of cognitive symptoms is associated with neuroimaging improvement in brain regions associated with learning and memory process. Acupuncture also ameliorates cognitive impairment in various animal models. Studies have further revealed that the cognition-improving effects of acupuncture are associated with the inhibition of cytokine-mediated neuronal cell apoptosis, inflammatory reaction and oxidative cellular injury and the effects in reducing cognitive symptoms are related to the protection of neuronal cells, improvement of electrophysiological activities of the hippocampus and brain cell proliferation. Moreover, acupuncture also displays a significant effect in facilitating the recovery of the brain at microstructural histopathological level in patients with cerebral infarction and in rats with transient focal cerebral ischemia. The investigators therefore hypothesize that acupuncture may be also effective in preventing and reducing chemotherapy caused cognitive impairment.

Recently, the investigators have developed a novel acupuncture stimulation called dense cranial electroacupuncture stimulation (DCEAS) on the basis of neuroanatomical rationale. In this mode, electrical stimulation is delivered on dense acupoints located on the forehead innervated by the trigeminal nerve. The trigeminal sensory pathway has much intimate fiber connections with brain regions associated with sensory, locomotor, visceral function, sleep, emotion, learning and memory. Therefore, DCEAS can effectively modulate brain functions. Over the past 5 years, the investigators have completed several clinical studies and demonstrated the benefits of DCEAS in the treatment of major depression, insomnia, OCD, postpartum depression and post-stroke depression. In the proposed study, a combination of DCEAS and body acupuncture will be employed to prevent and treat chemobrain in breast cancer patients.

Study Type

Interventional

Enrollment (Actual)

93

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518053
        • Department of Chinese Medicine, The University of Hong Kong - Shenzhen Hospital
      • Shenzhen, Guangdong, China, 518053
        • Department of Clinical Oncology, The University of Hong Kong - Shenzhen Hospital
  • Hong Kong
      • Hong Kong, Hong Kong
        • Department of Clinical Oncology, Queen Mary Hospital
      • Hong kong, Hong Kong
        • Department of Surgery, Queen Mary Hospital
      • Sai Ying Pun, Hong Kong
        • Department of Surgery, Tung Wah Hospital
    • N.t.
      • Sha Tin, N.t., Hong Kong
        • The Nethersole School of Nursing, The Chinese University of Hong Kong

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Chinese females aged 18 to 65 years;
  2. have a diagnosis of stage I-IIIa breast cancer; and
  3. are ready for orally administered or vein injection or both with Cytoxan-containing regimens as adjuvant chemotherapy before or after surgical treatment or in combination with other pharmacotherapy.

Exclusion Criteria:

  1. had chemotherapy in the last 2 years;
  2. have cardiac pacemakers, epilepsy or other unstable medical conditions;
  3. had investigational drug treatment within the past 6 months;
  4. alcoholism or drug abuse within the past 1 year; or
  5. have severe needle phobia.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Comprehensive acupuncture (CAI)
Breast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Dense cranial electroacupuncture stimulation (DCEAS) and Body acupuncture (BA).
Procedure: Dense cranial electroacupuncture stimulation

DCEAS is a is a novel stimulation mode in which electrical stimulation is delivered on acupoints located on the forehead.

Six pairs of acupoints are used: Baihui (GV20) and Yintang (EX-HN3), left Sishencong (EX-HN1) and Toulinqi (GB15), right Sishencong (EX-HN1) and Toulinqi (GB15), bilateral Shuaigu (GB8), bilateral Taiyang (EX-HN5), and bilateral Touwei (ST8).

Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation, followed by electrical stimulation (ITO ES-160, continuous waves at 2 Hz).

Other Names:
  • DCEAS
Procedure: Body acupuncture

Following acupoints are used: Shui-Gou (GV26), Shen-Men (HT7). He-Gu (LI4), Wai-Guan (TE5), Zhong-Wan (CV12), Guan-Yuan (CV4), Zu-San-Li (ST36), Feng-Long (ST40) and San-Yin-Jiao (SP6).

Disposable acupuncture needles (Hwato®, 0.30 mm in diameter and 25-40 mm in length) are inserted at a depth of 10-30 mm perpendicularly or obliquely into acupoints. Manual manipulation is then conducted to evoke needling sensation. No electrical stimulation is delivered.

Other Names:
  • BA
Drug: Cytoxan-containing chemotherapy regimens

Each subject shall receive oral administration or venous injection or both with adjuvant or neoadujuvant chemotherapy regimens, as decided by clinical oncologist.

In clinical practice, the most commonly used Cytoxan-containing regimens include but are not limit to:

AC (x4) [Adriamycin + Cytoxan], TC (x4) [Taxotere + Cytoxan], AC-P (4+4) [Adriamycin + Cytoxan + Paclitaxel], TAC (x6) [Taxotere + Adriamycin + Cytoxan], or AC-PH (4+4) [Adriamycin + Cytoxan + Paclitaxel + Herceptin].

Other Names:
  • Chemo
Sham Comparator: Least acupuncture stimulation (LAS)
Breast cancer patients receiving Cytoxan-containing chemotherapy regimens (Chemo) will receive Least acupuncture stimulation (LAS)
Drug: Cytoxan-containing chemotherapy regimens

Each subject shall receive oral administration or venous injection or both with adjuvant or neoadujuvant chemotherapy regimens, as decided by clinical oncologist.

In clinical practice, the most commonly used Cytoxan-containing regimens include but are not limit to:

AC (x4) [Adriamycin + Cytoxan], TC (x4) [Taxotere + Cytoxan], AC-P (4+4) [Adriamycin + Cytoxan + Paclitaxel], TAC (x6) [Taxotere + Adriamycin + Cytoxan], or AC-PH (4+4) [Adriamycin + Cytoxan + Paclitaxel + Herceptin].

Other Names:
  • Chemo
Procedure: Least acupuncture stimulation
The acupoints chosen are less related to the treated syndromes based on Traditional Chinese Medicine (TCM) theory; the number of acupoints used and the intensity of electrical stimulation are also lower than the comprehensive acupuncture regimen. The following 6 acupoints will be used in LAS control: bilateral Tong-Tian (GB17), bilateral Shou San-Li (LI10) and bilateral Fu-Yang (BL59). Electrical stimulation will be only performed on bilateral Tong-Tian (GB17) and the intensities are adjusted to a level at which patients just start feeling the stimulation.
Other Names:
  • LAS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in cognitive function (objective measurement)
Time Frame: Baseline, 2 week, 4 week, 6 week, 8 week
The Montreal Cognitive Assessment (MoCA) of corresponding dialects will be used as an objective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
Baseline, 2 week, 4 week, 6 week, 8 week
Changes in cognitive function (subjective measurement)
Time Frame: Baseline, 2 week, 4 week, 6 week, 8 week
The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) of corresponding dialects will be used as a subjective measurement for subjects' cognitive function. Assessments will be conducted at baseline and every 2 weeks thereafter.
Baseline, 2 week, 4 week, 6 week, 8 week

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in quality of Life - composite measure
Time Frame: Baseline, 4 week, 8 week
The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30+BR23) and Functional Assessment of Cancer Therapy-Breast (FACT-B) of corresponding dialects will be used for assessment on quality of life. Both of them will be used as the former focuses on physical function, while the latter emphasizes on emotional well-being. Assessments will be conducted at baseline and every 4 weeks thereafter.
Baseline, 4 week, 8 week
Changes in illness related fatigue measured by FACIT-Fatigue
Time Frame: Baseline, 4 week, 8 week
As fatigue is a common co-morbidity observed in patients receiving chemotherapy, it will be measured using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) of corresponding dialects. Assessments will be conducted at baseline and every 4 weeks thereafter.
Baseline, 4 week, 8 week
Changes in chemo adverse effects - composite measure
Time Frame: Baseline, 4 week, 8 week
Adverse side effects will be assessed using Functional Assessment of Cancer Therapy questionnaires (FACT-Taxane, FACT-BRM) of corresponding dialects. Assessments will be conducted at baseline and every 4 weeks thereafter.
Baseline, 4 week, 8 week
Changes in subject perception of chemotherapy treatment measured by FACIT-TS-G
Time Frame: Baseline, 4 week, 8 week
To determine whether acupuncture can reduce the adverse effects of chemo-therapy treatment and therefore increase subject acceptance, subject treatment satisfaction will be assessed using Functional Assessment of Chronic Illness Therapy questionnaire (FACIT-TS-G). Assessments will be conducted at baseline and every 4 weeks thereafter.
Baseline, 4 week, 8 week

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Hong Kong

Collaborators

Chinese University of Hong Kong

Investigators

  • Principal Investigator: Zhang-Jin Zhang, MMed, PhD, School of Chinese Medicine, The University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2015

Primary Completion (Actual)

December 1, 2018

Study Completion (Actual)

March 1, 2019

Study Registration Dates

First Submitted

May 15, 2015

First Submitted That Met QC Criteria

May 26, 2015

First Posted (Estimate)

May 29, 2015

Study Record Updates

Last Update Posted (Actual)

May 20, 2019

Last Update Submitted That Met QC Criteria

May 17, 2019

Last Verified

May 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UW 14-206

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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