Acupuncture Prevents Chemobrain in Breast Cancer Patients

Breast Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02457039
• Other study ID #: UW 14-206
• Status: Completed
• Phase: N/A
• Start date: October 2015
• Est. completion date: March 2019

Study information

• Verified date: May 2019
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 93
• Est. completion date: March 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms
• Chemo-brain
• Cognitive Dysfunction
• Drug-Related Side Effects and Adverse Reactions
• Mild Cognitive Impairment

Intervention

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).
• 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.
• 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.

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].

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
The University of Hong Kong	Chinese University of Hong Kong

Countries where clinical trial is conducted

China,  Hong Kong, 

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* Note: There are 39 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in cognitive function (objective measurement)	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
Primary	Changes in cognitive function (subjective measurement)	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	Changes in quality of Life - composite measure	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
Secondary	Changes in illness related fatigue measured by FACIT-Fatigue	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
Secondary	Changes in chemo adverse effects - composite measure	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
Secondary	Changes in subject perception of chemotherapy treatment measured by FACIT-TS-G	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