Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study

Studies have suggested that chemotherapy treatment for breast cancer may change the way the
brain functions. As a result, patients who receive chemotherapy for breast cancer may
experience problems with their attention, learning, and memory that they did not have before
receiving chemotherapy. The investigators have found that nicotine treatment can help other
types of patients with similar difficulties with attention, learning, and memory. Nicotine is
a naturally occurring substance found in tobacco and is known to interact with nerve cells in
the brain that are important for functions like learning and memory, and has been studied in
a number of disorders. This study is designed to test whether nicotine treatment is helpful
for learning and memory problems after chemotherapy for breast cancer.

This study will be a randomized, placebo-controlled pilot study to evaluate the effect of
transdermal nicotine to 1) reduce subjective complaints and 2) enhance cognitive performance
on laboratory measures of cognitive performance in breast cancer patients with persistent
chemotherapy-related cognitive impairment (CRCI), a condition also known as "chemo brain."
Participants will be randomized to either placebo or active compound (50/50) for the 6-week
treatment portion of the study. Participants will be assessed before, during, and at the end
of treatment. At the end of the 8-week study, participants will have the option to take part
in the open-label portion of the study for an additional 6 weeks.

Inclusion Criteria:

- All participants will:

1. Be between 35 and 80 years of age,

2. Have been diagnosed with noninvasive or invasive (Stage 1, 2, or 3A) breast
cancer,

3. Have undergone treatment with systemic chemotherapy within the last 1-5 years,

4. Endorse persistent CRCI subjective complaints,

5. Be non-smokers (no nicotine use within the last 5 years),

6. Have no active cardiac, neurologic, or psychiatric illness, and

7. Fluent in and able to read English.

Exclusion Criteria:

- Participants will be excluded for:

1. Any active neurologic and/or psychiatric disease, history of significant head
trauma followed by persistent neurologic deficits, or known structural brain
abnormalities,

2. Current major depression or another major psychiatric disorder as described in
DSM-5 (use of CNS active medications (e.g. antidepressants) will be permitted,
provided dosing has been stable for at least 3 months),

3. Any history of alcohol or substance abuse or dependence within the past 2 years
(DSM-5 criteria),

4. Any significant systemic illness or unstable medical condition which could lead
to difficulty complying with the protocol including:

- History of myocardial infarction in the past year or unstable, severe cardiovascular
disease including angina or CHF with symptoms at rest, or clinically significant
abnormalities on the ECG

- Clinically significant and/or unstable pulmonary, gastrointestinal, hepatic, or renal
disease

- Insulin-requiring diabetes or uncontrolled diabetes mellitus,

- Uncontrolled hypertension (systolic BP> 170 or diastolic BP> 100), 5. Use of any
investigational drugs within 30 days or 5 half-lives, whichever is longer, prior to
screening, and 6. Use of any drugs with pro-cholinergic properties (e.g. donepezil).