Transcranial Direct Current Stimulation (tDCS) to Improve Fatigue and Cognitive Function

Study Overview
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Brief Summary
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This research is being done to determine whether transcranial direct current stimulation (tDCS) can improve fatigue and certain thinking skills in women with breast cancer receiving chemotherapy. Transcranial Direct Current Stimulation is a form of brain stimulation during which low amounts of electrical current are delivered to the brain using electrodes attached to the scalp. The idea of using electrical stimulation to affect neurological symptoms has been around for more than 100 years with the first reported use in 1801. Since the 1960s, tDCS has been used in research for a variety of reasons including stroke rehabilitation, memory enhancement and for depression. People aged 18 or older who are currently receiving chemotherapy with docetaxel and who are experiencing fatigue may join.

Detailed Description
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Fatigue and cognitive impairment are commonly reported symptoms associated with impaired quality of life (QOL) and productivity in breast cancer patients receiving chemotherapy. Working memory, the brain's system for temporarily storing and manipulating information required to carry out more complex cognitive tasks, is particularly affected by cancer and its treatment. In women who have undergone chemotherapy for breast cancer, neuroimaging studies show structural brain changes as well as functional inefficiencies in a region critical for working memory, the left dorsolateral prefrontal cortex (DLPFC). Fatigue appears to play a critical role in the recruitment of the DLPFC during cognitive tasks. Transcranial direct current stimulation (tDCS) is a safe, portable, non-invasive form of electrical brain stimulation that enhances neuronal transmission beneath scalp electrodes. Our group and others have shown that when applied to the left DLPFC, tDCS improves energy in patients with fatiguing medical conditions and that it improves cognition in both healthy adults and those with neurodegenerative diseases. The proposed feasibility trial is a randomized, sham-controlled, double-blind experiment. Eligible individuals will be ≥ age 18 years with stage I-IV breast cancer undergoing docetaxel-based chemotherapy every 3 weeks (at least 60 mg/m2 dose) with or without HER2-targeted therapy who self-report moderate or severe fatigue (rated ≥ 4 on a scale of 0-10) during at least 3 days of their most recent chemotherapy cycle. Participants will be randomized to either active or sham tDCS and will undergo 5 consecutive treatments of daily tDCS beginning the Monday following the first day of their on-study chemotherapy cycle. Active treatment will consist of a mild electrical current (2mA) administered via saline-soaked sponge electrodes placed along the intact scalp for 30 minutes a day for five days. Sham stimulation will involve brief delivery of current in a manner that does not result in changes in neuronal firing patterns, but that is perceived as active treatment by participants. Participants will complete self-report measures of fatigue, cognitive function and QOL along with cognitive testing at the beginning and end of the five-day intervention. Subjective fatigue, QOL and cognitive function will be also assessed prior to administration of the next cycle of chemotherapy. Total time on study will be approximately 3 weeks (one cycle of chemotherapy). Daily subjective fatigue will be monitored throughout participation.

Official Title
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Transcranial Direct Current Stimulation (tDCS) to Improve Fatigue and Cognitive Function During Breast Cancer Chemotherapy: A Feasibility Study

Conditions
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Breast Cancer, Fatigue

Intervention / Treatment
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* Other: transcranial direct current stimulation
* Other: sham transcranial direct current stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women or men, 18 years of age or older Stage I-IV breast cancer receiving docetaxel-based chemotherapy (at least 60 mg/m2) every 21 days • Docetaxel may be administered concurrently with other chemotherapy agents and/or with HER2 targeted therapies at the discretion of the treating provider Fatigue: Self-report of moderate or severe fatigue on at least 3 days during the prior cycle of docetaxel-based chemotherapy, defined as ≥ 4 on a 0 (no fatigue) to 10 (worst fatigue imaginable) scale. Able and willing to complete study tasks as evidenced by at least the following according to the assessment of a study team member: fluent English speaker; hearing and language comprehension; and, sufficient literacy to complete study forms and questionnaires Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form. Exclusion Criteria: Dementia as assessed by a MMSE score < 24 on initial screening. Known pregnancy or nursing. Any of the following: known diagnosis of schizophrenia or bipolar disorder, seizure disorder, pacemaker, hearing aids, any metal implanted in the head, untreated hypothyroidism, aphasia, delirium, known neurologic disorder which affects cognitive function, prior traumatic brain injury, known heart failure • Note: presence of a mediport is not an exclusion criteria Use of the following medications for seven days prior to and during study participation: Stimulant medications Carbamazepine/Tegretol Cough/cold medicines (e.g. Dextromethorphan, Triaminic, Robitussin, Vics Formula 44) Flunarizine/Sibelium Propanolol/Inderal Sulpiride Pergolide Rivastigmine/Exelon Carbidopa/levodopa or levodopa Ropinirole/Requip Nicotine patch Use of illicit drugs for seven days prior to and during study participation. Self-reported consumption of > 14 alcoholic drinks per week or positive screening on the CAGE questionnaire in relation to the past year. NOTE: A single, standard alcoholic drink is defined as 10 grams of alcohol, which is equivalent to 285 mL of beer, 530 mL of light beer, 100 mL of wine or 30 mL of liquor. Skin conditions involving open sores on the scalp that would prevent proper application of the electrodes. Hairstyles that obstruct placement of the electrodes including cornrows, dreadlocks, braids or other hair accessories that cannot be removed. Known history of brain metastases or leptomeningeal carcinomatosis (even if adequately treated) Prior brain surgery Other medical or other condition(s) that in the opinion of the investigators might compromise the objectives of the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: The proposed feasibility trial is a randomized, sham-controlled, double-blind experiment.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active tDCS<br>Active transcranial direct current stimulation: Participants will undergo five consecutive days (Monday-Friday) of active stimulation beginning the Monday after their on-study chemotherapy administration. Questionnaires and cognitive assessment will be completed on the first and last days of stimulation (i.e., Monday and Friday). On all 5 days, participants will engage in cognitive tasks while receiving stimulation (either active or sham) in order to maximize stimulation effects 43. In order to assess for duration of subjective effects, participants will complete self-report measures of subjective fatigue, cognitive function and QOL immediately prior to their next chemotherapy (approximately 10-14 days after completion of stimulation). | Other: transcranial direct current stimulation<br>* Active treatment will consist of a mild electrical current (2mA) administered via saline-soaked sponge electrodes placed along the intact scalp for 30 minutes a day for five days.<br>* Other names: tDCS;|
| Sham Comparator: Sham tDCS<br>Sham transcranial direct current stimulation: Participants will undergo five consecutive days (Monday-Friday) of sham stimulation beginning the Monday after their on-study chemotherapy administration. Questionnaires and cognitive assessment will be completed on the first and last days of stimulation (i.e., Monday and Friday). On all 5 days, participants will engage in cognitive tasks while receiving stimulation (either active or sham) in order to maximize stimulation effects 43. In order to assess for duration of subjective effects, participants will complete self-report measures of subjective fatigue, cognitive function and QOL immediately prior to their next chemotherapy (approximately 10-14 days after completion of stimulation). | Other: sham transcranial direct current stimulation<br>* Sham stimulation will involve brief delivery of current in a manner that does not result in changes in neuronal firing patterns, but that is perceived as active treatment by participants.<br>* Other names: sham stimulation;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of tDCS | Evaluation of the feasibility of 5 consecutive days of tDCS in breast cancer patients receiving docetaxel-based chemotherapy. Feasibility will be evaluated by assessing the proportion of study participants who complete at least 4 of 5 days of the planned tDCS intervention (active or sham) during docetaxel-based chemotherapy. If >80% of participants complete 4 of the 5 planned stimulation sessions, tDCS will be defined as feasible. | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | Participants will complete self-report measures of fatigue. The Multidimensional Fatigue Symptom Inventory 30-item Short Form (MFSI-SF) will serve as the primary measurement tool for the assessment of subjective fatigue. This questionnaire assesses participants' subjective ratings across five subscales: general fatigue, physical fatigue, emotional fatigue, mental fatigue, and vigor. Responses are provided on 5-point Likert-like scales addressing the extent to which each symptom was experienced during the preceding 7 days ranging from 0 (not at all) to 4 (extremely). The subscale scores are obtained by summing scores within each subscale. The MFSI-SF total score is obtained by subtracting the vigor subscale score from the sum of the four fatigue subscales. Scores range from -36 to 144. The MFSI-SF is well validated in breast cancer patients. Breast cancer patients with fatigue produce an average score of 14.7 ± 15.2. The MFSI-SF takes approximately 5 minutes to complete. | Day 1, Day 5, and at End of study (approximately 3 weeks) | 
| Subjective Cognitive Function | Participants will self-report measures of cognitive function at the beginning and end of the five-day intervention. The endpoint for subjective cognition will be scores on the FACT-Cog, a 37-item self-report measure. Responses are provided on 5-point Likert-like scales addressing the frequency with which each type of cognitive difficulty occurred from 0 (never) to 4 (several times a day) over the prior seven days. Two additional subscales address noticeability or comments from others regarding cognition and effect of perceived cognitive impairment on quality of life. These are rated on 5-point Likert-like scales ranging from 0 (not at all) to 4 (very much). The total FACT-Cog score is obtained by summing the individual subscale scores and ranges from 0 to 148. Breast cancer patients produce a mean FACT-Cog total score of 119.0 ± 23.3.The FACT-Cog takes approximately 5 minutes to complete. | Day 1, Day 5, and at end of study (approximately 3 weeks) | 
| Objective Cognitive Function | Objective cognitive function from baseline (prior to tDCS) to completion of tDCS will be assessed. The measurement tool for objective cognitive function for this objective will be the Paced Auditory Serial Addition Test (PASAT) of working memory. The PASAT is working memory task that has been well-validated medical populations including breast cancer. Test administration involves the aural presentation of single digits via computer in order to ensure a standardized rate of stimulus presentation. Stimuli are presented every three seconds (trial 1) or every two seconds (trial 2). Participants add each new digit to the one immediately prior as the test continues to present stimuli. The test score reflects the total number of correct sums given (out of 60 possible) in each trial. Two equivalent, alternative PASAT forms will be used to minimize practice effects. The test takes approximately 10 minutes to complete. | Day 1 and Day 5 | 
| Quality of Life | The measurement tool for QOL will be the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). The impact of tDCS on QOL will be assessed by the EORTC QLQ-C30. This 30-item questionnaire includes five functional scales (physical, role, emotional, social and cognitive), three symptom scales (fatigue, nausea/vomiting and pain), a global health status scale and six single items (dyspnea, constipation, diarrhea, appetite, sleep and financial difficulty). The first 28 questions are answered using a Likert-like scale ranging from 1, not at all, to 4, very much. The last two questions are answered on a Likert-like scale ranging from 1, poor to 7, excellent. The recall period is 7 days. The EORTC QLQ-C30 has been extensively used as a quality of life measure in breast cancer clinical trials and is well validated in the breast cancer population. The EORTC QLQ-C30 takes approximately 5 minutes to complete. | Day 1, Day 5, End of study (approximately 3 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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docetaxel, Stage I - IV, chemotherapy