Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Behaviors and Mental Disorders

Substance Related Disorders

Breast Neoplasms

Cognitive Dysfunction

Chemotherapy-Related Cognitive Impairment

Cognition Disorders

Neurocognitive Disorders

Mental Disorders

Psychotic Disorders

Drug-Related Side Effects and Adverse Reactions

Chemically-Induced Disorders

All Drugs and Chemicals

Central Nervous System Stimulants

Nicotine

Nicotinic Agonists

Cholinergic Agents

Neurotransmitter Agents

Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:

Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal

Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal

Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.

Transdermal nicotine

Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

Placebo Transdermal Patch

Paul A Newhouse, M.D.

The purpose of this study is to evaluate the use of a nicotine patch as a treatment for problems with attention, learning and memory in breast cancer patients who are 1-5 years post chemotherapy.

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.

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

The Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scale will be used to monitor change in CRCI subjective complaints.

This instrument has been used to monitor change in CRCI subjective complaints in previous studies and demonstrates good internal consistency, test-retest reliability, and discriminant and convergent validity. Specifically, the PCI subscale was used as the primary outcome measure.

The FACT-Cog PCI consists of 20 items and has a minimum score of 0 and total possible score of 72. Higher scores indicate better cognitive functioning.

The PCI evaluates memory, concentration, mental acuity, verbal fluency, functional interference, and multitasking ability.

Visit 3 is the 3-week visit, Visit 4 is the 6-week visit, and Visit 5 is the 8-week visit.

Change scores were calculated as follow

The secondary outcome measure was the computerized Conners Continuous Performance Test (CPT), which measures sustained attention and vigilance. Participants see a series of letters appearing one at a time on a computer screen and they press a button for every letter that appears on the screen, except for "X". Lower scores indicate better performance.

Scores on the CPT are calculated using the each participant's performance on the task (defined as reaction time (in ms) standard error/interstimulus interval). Change scores from baseline are then calculated. A decrease in CPT score = improvement.

\*This is not a clinical measure. This is a research measure of reaction time variability and therefore there is no clinical interpretation and no defined score range.\*

Vanderbilt University Medical Center

Professor of Psychiatry, Pharmacology, and Medicine

Adverse events were recorded and categorized by body system, event type, attribution, frequency, severity, and course. AEs were assessed across all double-blind study visits and categorized according to body system for all participants who received at least one dose of patches (nicotine n = 12, placebo n = 13).

Nicotine will be delivered by a transdermal patch delivery system for topical application. Each patch will contain approximately 1.75mg nicotine/cm2, and releases 7, and 14mg of nicotine, respectively, over 24 hours. Patches will be applied for 16 hours per day. Participants will be titrated over the course of the 6-week treatment period in order to avoid initial side effects as follows:

Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal

Transdermal nicotine: Nicotine patches are currently FDA approved for smoking cessation. Nicotine has effects that have been well studied for many years. Studies have shown that nicotine by itself does not appear by itself to be cancer causing. The use of the nicotine patch is not expected to increase risk of breast cancer recurrence.

Transdermal Nicotine

Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal

Placebo Transdermal Patch

Placebo

Total

Age, Categorical

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Cancer Type

Cancer Stage

Chemotherapy

Surgery

Radiation

Cancer Treatment Received

Current Endocrine Therapy

Post-Menopausal Status

Small sample size numbers; treatment duration of 6-weeks may not have been enough time to distinguish between a drug and placebo response; 14mg may not have been a sufficient dose to fully test this hypothesis.

Dr. Paul A. Newhouse

For the Primary Aim (Specific Aim 1), a mixed-models repeated measures ANOVA was used to assess the interaction of treatment group (nicotine, placebo) with time (Visit), using change from baseline PCI FACT-Cog score (Visit 3, Visit 4, and Visit 5) as the dependent measure.

Visit 3 PCI Change from Baseline Score (3-Weeks)

Visit 4 PCI Change from Baseline Score (6-Weeks)

Visit 5 PCI Change from Baseline Score (8-Weeks)

Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale

For the Secondary Aim (Specific Aim 2), a mixed-models repeated measures ANOVA was used to assess the interaction of treatment group (nicotine, placebo) with time (Visit), using change from baseline CPT Scores (Visit 3, Visit 4, and Visit 5) as the dependent measure.

Visit 3 CPT Change from Baseline Score (3-Weeks)

Visit 4 CPT Change from Baseline Score (6-Weeks)

Visit 5 CPT Change from Baseline Score (8-Weeks)

Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

Week 1: ½ 7 mg patch per day, Week 2: 7 mg patch per day, Weeks 3-4: ¾ 14 mg patch per day, Weeks 5-6: 14 mg per day, Weeks 7-8: Treatment withdrawal

Placebo Transdermal Patch: Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study	NCT02312934	Chemo Brain Chemotherapy-re... Chemo Fog Breast Cancer Chemobrain	Transdermal nic... Placebo Transde...	35 Years - 80 Years	Vanderbilt University Medical Center
Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study	NCT02312934	Chemo Brain Chemotherapy-re... Chemo Fog Breast Cancer Chemobrain	Transdermal nic... Placebo Transde...	35 Years - 80 Years	Vanderbilt University Medical Center

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