Cranial Stimulation for Chemotherapy Symptoms in Breast Cancer

Study Overview
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Brief Summary
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RATIONALE: Cranial microcurrent electrical stimulation (CES) is mild electrical current received through electrodes placed on the earlobes. CES may lessen symptoms in women with breast cancer receiving chemotherapy. It is not yet known whether CES is more effective than sham therapy in reducing symptoms caused by chemotherapy in women with breast cancer. PURPOSE: This randomized phase III trial is studying mild electrical stimulation to see how well it works compared with sham therapy in reducing symptoms caused by chemotherapy in women with stage I, stage II, or stage IIIA breast cancer receiving chemotherapy.

Detailed Description
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OBJECTIVES: Primary To compare the effects of cranial microcurrent electrical stimulation (CES) vs sham CES over time on symptoms of depression, anxiety, fatigue, pain, and sleep disturbances in women with stage I-IIIA breast cancer receiving adjuvant chemotherapy. Secondary To explore the relationships among selected markers of inflammation (e.g., tumor necrosis factor alpha, interleukin-6, interleukin-1β, and C-reactive protein), symptoms, and quality of life. To examine whether the symptoms of depression, anxiety, fatigue, sleep disturbances, and pain form a cluster. To examine the effects of CES on quality of life. OUTLINE: Patients are stratified according to chemotherapy schedule (every 2 weeks for 8 courses vs every 3 weeks for 6 courses). Patients are randomized to 1 of 2 treatment arms. Arm I (cranial microcurrent electrical stimulation [CES]): Patients receive a CES unit (Alpha-Stim® 100 Microcurrent Stimulator) that passes microcurrent levels of biphasic electrical stimulation via ear-lobe electrodes. The CES unit is preset to provide 1 hour of 100 μA (sub-sensory level), modified square-wave biphasic stimulation on a 50% duty cycle at .05 Hz, and to automatically turn off at the end of 1 hour. Patients use their CES unit once daily in weeks 1-18. Arm II (sham CES): Patients receive a CES unit as in arm I, but the ear-lobe electrodes do not pass electrical current. Patients use their CES unit once daily in weeks 1-18. Patients complete symptom questionnaires (e.g., the Hospital Anxiety and Depression Scale, the Brief Pain Inventory Short-Form, the Brief Fatigue Inventory, and the General Sleep Disturbance Scale) weekly in weeks 1-18. Patients also complete a quality-of-life questionnaire in weeks 1, 7, and 18. Blood samples are collected in weeks 1, 7, and 18 and analyzed for cytokines (e.g., tumor necrosis factor alpha, interleukin-6, and interleukin-1β) and C-reactive protein.

Official Title
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Cranial Stimulation for Chemotherapy Symptoms in Breast Cancer

Conditions
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Anxiety Disorder, Breast Cancer, Depression, Fatigue, Pain, Sleep Disorders

Intervention / Treatment
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* Procedure: energy-based therapy
* Procedure: sham intervention


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of stage I-IIIA breast cancer Scheduled to receive adjuvant chemotherapy Hormone receptor status not specified PATIENT CHARACTERISTICS: Pre, peri, or post-menopausal ECOG performance status 0-1 No dementia No active psychosis No history of seizure disorder No implanted electrical device PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior chemotherapy No initiation of a medication regimen for depression or other psychiatric condition within the past 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (cranial microcurrent electrical stimulation [CES])<br>Patients receive a CES unit (Alpha-Stim® 100 Microcurrent Stimulator) that passes microcurrent levels of biphasic electrical stimulation via ear-lobe electrodes. The CES unit is preset to provide 1 hour of 100 μA (sub-sensory level), modified square-wave biphasic stimulation on a 50% duty cycle at .05 Hz, and to automatically turn off at the end of 1 hour. Patients use their CES unit once daily in weeks 1-18. | Procedure: energy-based therapy<br>* Given once a day for 18 weeks<br>|
| Sham Comparator: Arm II (sham CES)<br>Patients receive a CES unit as in arm I, but the ear-lobe electrodes do not pass electrical current. Patients use their CES unit once daily in weeks 1-18. | Procedure: sham intervention<br>* Given once a day for 18 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of CES as Compared to Sham CES on Symptoms of Depression, Anxiety, Fatigue, Pain and Sleep Disturbances in Women Receiving Adjuvant Chemotherapy for Early-stage Breast Cancer | Using Hospital Anxiety and Depression Scale (HADS) a 14 item scale, 7 relate to anxiety, 7 to depression; each item is scored from 0-3, a person can score 0 to 21 for either anxiety or depression (0 is best and 21 is worst), Brief Pain Inventory (BPI) short-form measures the intensity and interference of pain in the patient's life; 12 questions with 0 (does not interfere) to 10 (completely interferes); mean will be used as the measure of pain; Brief Fatigue Inventory (BFI) assess the severity and impact of cancer-related fatigue. Has 9 questions with 0 (does not interfere) to 10 (completely interferes), the total mean score is the mean of the 9 questions; severe fatigue can be defined as a score of 7 or higher, General Sleep Disturbance Scale (GSDS) 21 items to evaluate sleep issues (0=never to 7=every day); the 21 items are summed to produce a total score of 9=no sleep disturbance to 137=extreme sleep disturbance . Used standard questionnaire | Up to 2 weeks afer completion of study treatment, for up to 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Examine Whether the Symptoms of Depression, Anxiety, Fatigue, Sleep Disturbances and Pain Form a Cluster. | Examine correlations between the symptoms at baseline to determine a general pattern of association. Factor analysis (a statistical method used to describe variability among observed, correlated variables in terms of a potentially lower number of unobserved variables called factors) was performed to examine how these 5 symptoms cluster. A principal component factor analysis was performed on the correlation matrix for the symptom scores of anxiety, depression, pain, fatigue and sleep disturbance at up to two weeks after completion of study treatment, up to 8 months). For each analysis two factors were retained that explained 74% of the variability for the baseline symptom scores, 79% of the variability of the symptom scores at the midpoint and 78% of the variability in symptom scores at study completion. A varimax rotation was utilized and the factor loadings from the varimax rotation were reported. | up to 2 weeks after completion of study treatment, for up to 8 months | 
| Means and Standard Deviations of Biomarkers Log(CRP pg/ml), Log(IL-1b pg/ml), Log(IL-6 pg/ml) and Log(TNF-a pg/ml). | Simple correlations will be computed at Midpoint Chemotherapy for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Baseline | 
| Relationships Among Biomarkers Log(CRP pg/ml), Log(IL-1b pg/ml), Log(IL-6 pg/ml) and Log(TNF-a pg/ml). | Simple correlations will be computed at Baseline for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Baseline | 
| Relationships Among Anxiety, Depression, Fatigue, Pain and Sleep Scores - Means at Baseline | Measured using Hospital Anxiety and Depression Scale (HADS) a fourteen item scale, 7 relate to anxiety and 7 to depression; each item is scored from 0-3, this means a person can score 0 to 21 for either anxiety or depression (0 is best and 21 is worst), Brief Pain Inventory (BPI) short-form measures the intensity of pain and interference of pain in the patient's life; 12 questions with 0 (does not interfere) to 10 (completely interferes); mean will be used as the measure of pain; Brief Fatigue Inventory (BFI) assess the severity and impact of cancer-related fatigue. it has 9 questions with 0 (does not interfere) to 10 (completely interferes); severe fatigue can be defined as a score of 7 or higher, General Sleep Disturbance Scale (GSDS) 21 items to evaluate sleep issues (0=never to 7=every day); the 21 items are summed to produce a total score of 9=no sleep disturbance to 137=extreme sleep disturbance . Used standard questionnaire scoring system. | Baseline | 
| Relationships Among Symptom Scores - Correlations at Baseline Chemotherapy | Simple correlations will be computed at Baseline Chemotherapy for symptoms. | Baseline | 
| Relationships Among Quality of Life Scores - Means at Baseline | Measured using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). A 44-item self-report instrument designed to measure multidimensional quality of life in patient with breast cancer. 0=not at all to 4=very much. Utilized standard questionnaire scoring system. The items are summed to produce a total score 0=not at all to 176=very much. The FACT-B BCA has 10 questions that range from 0 (not at all) to 4 (very much); thus the FACT-B BCA ranges from 0 to 40. Both the FACT-B and FACT-BCA are scored so that high scores indicate higher levels of quality of life. | Baseline | 
| Relationships Among Quality of Life Scores - Correlations at Baseline | Simple correlations will be computed at Baseline for quality of life scores. | Baseline | 
| Mean and Standard Deviation of Biomarkers Log(CRP pg/ml), Log(IL-1b pg/ml), Log(IL-6 pg/ml) and Log(TNF-a pg/ml). | Simple correlations will be computed at Midpoint Chemotherapy for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Midpoint Chemotherapy, up to 4 months | 
| Relationships Among Biomarkers Log (CRP), Log (IL-1B), Log (IL6), and Log (TNF-a) - Correlations at Midpoint Chemotherapy | Simple correlations will be computed at Midpoint Chemotherapy for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Midpoint Chemotherapy, up to 4 months | 
| Relationships Among Anxiety, Depression, Fatigue, Pain and Sleep Scores - Means at Midpoint Chemotherapy | Measured using Hospital Anxiety and Depression Scale (HADS) a fourteen item scale, 7 relate to anxiety and 7 to depression; each item is scored from 0-3, this means a person can score 0 to 21 for either anxiety or depression (0 is best and 21 is worst), Brief Pain Inventory (BPI) short-form measures the intensity of pain and interference of pain in the patient's life; 12 questions with 0 (does not interfere) to 10 (completely interferes); mean will be used as the measure of pain; Brief Fatigue Inventory (BFI) assess the severity and impact of cancer-related fatigue. it has 9 questions with 0 (does not interfere) to 10 (completely interferes); severe fatigue can be defined as a score of 7 or higher, General Sleep Disturbance Scale (GSDS) 21 items to evaluate sleep issues (0=never to 7=every day); the 21 items are summed to produce a total score of 9=no sleep disturbance to 137=extreme sleep disturbance . Used standard questionnaire scoring system. | Midpoint Chemotherapy, up to 4 months | 
| Relationships Among Symptom Scores - Correlations at Midpoint Chemotherapy | Simple correlations will be computed at Midpoint Chemotherapy for symptoms. | Midpoint Chemotherapy, up to 4 months | 
| Relationships Among Quality of Life Scores - Means at Midpoint Chemotherapy | Measured using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). A 44-item self-report instrument designed to measure multidimensional quality of life in patient with breast cancer. 0=not at all to 4=very much. Utilized standard questionnaire scoring system. The items are summed to produce a total score 0=not at all to 176=very much. The FACT-B BCA has 10 questions that range from 0 (not at all) to 4 (very much); thus the FACT-B BCA ranges from 0 to 40. Both the FACT-B and FACT-BCA are scored so that high scores indicate higher levels of quality of life. | Midpoint Chemotherapy, up to 4 months | 
| Relationships Among Quality of Life Scores - Correlations at Midpoint Chemotherapy | Simple correlations will be computed at Midpoint Chemotherapy for quality of life scores. | Midpoint Chemotherapy, up to 4 months | 
| Mean and Standard Deviation of Biomarkers Log(CRP pg/ml), Log(IL-1b pg/ml), Log(IL-6 pg/ml) and Log(TNF-a pg/ml). | Simple correlations will be computed after completion of study treatment for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Up to 2 weeks after completion of study treatment, for up to 8 months | 
| Relationships Among Biomarkers Log (CRP), Log (IL-1B), Log (IL6), and Log (TNF-a) - Correlations at End of Treatment | Simple correlations will be computed at Chemotherapy End of Treatment for the log transformed biomarker values; IL1-β, IL-6, TNF-α, CRP. These are the biomarkers of inflammation. | Up to 2 weeks afer completion of study treatment, for up to 8 months | 
| Relationships Among Anxiety, Depression, Fatigue, Pain and Sleep Scores - Means at End of Chemotherapy | Measured using Hospital Anxiety and Depression Scale (HADS) a fourteen item scale, 7 relate to anxiety and 7 to depression; each item is scored from 0-3, this means a person can score 0 to 21 for either anxiety or depression (0 is best and 21 is worst), Brief Pain Inventory (BPI) short-form measures the intensity of pain and interference of pain in the patient's life; 12 questions with 0 (does not interfere) to 10 (completely interferes); mean will be used as the measure of pain; Brief Fatigue Inventory (BFI) assess the severity and impact of cancer-related fatigue. it has 9 questions with 0 (does not interfere) to 10 (completely interferes); severe fatigue can be defined as a score of 7 or higher, General Sleep Disturbance Scale (GSDS) 21 items to evaluate sleep issues (0=never to 7=every day); the 21 items are summed to produce a total score of 9=no sleep disturbance to 137=extreme sleep disturbance . Used standard questionnaire scoring system. | Up to 2 weeks afer completion of study treatment, for up to 8 months | 
| Relationships Among Symptom Scores - Correlations at End of Chemotherapy | Simple correlations will be computed at end of Chemotherapy for symptoms. | Up to 2 weeks afer completion of study treatment, for up to 8 months | 
| Effects of Treatment on Quality of Life - Means at End of Treatment | Measured using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). A 44-item self-report instrument designed to measure multidimensional quality of life in patient with breast cancer. 0=not at all to 4=very much. Utilized standard questionnaire scoring system. The items are summed to produce a total score 0=not al all to 176=very much. The FACT-B BCA has 10 questions that range from 0 (not at all) to 4 (very much); thus the FACT-B BCA ranges from 0 to 40. Both the FACT-B and FACT-BCA are scored so that high scores indicate higher levels of quality of life. | up to 2 weeks after completion of study treatment, for up to 8 months | 
| Relationships Among Quality of Life Scores - Correlations at End of Chemotherapy | Simple correlations will be computed at End of Chemotherapy for quality of life scores. | Up to 2 weeks afer completion of study treatment, for up to 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, anxiety disorder, fatigue, pain, sleep disorders, stage IA breast cancer, stage IB breast cancer, stage II breast cancer, stage IIIA breast cancer