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

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.

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