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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Transdermal Nicotine | Experimental | 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 |
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| Placebo | Placebo Comparator | 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Transdermal nicotine | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale | 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 | Baseline to 8-Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Conners Continuous Performance Test | 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.* |
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Inclusion Criteria:
All participants will:
Exclusion Criteria:
Participants will be excluded for:
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).
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| Name | Affiliation | Role |
|---|---|---|
| Paul A Newhouse, M.D. | Vanderbilt University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Center for Cognitive Medicine at Vanderbilt University | Nashville | Tennessee | 37212 | United States |
Of the 106 people pre-screened for the study, 37 attended the initial screening visit. Twenty-two participants met entry criteria and were randomized. Participants that were not randomized were excluded from the study because they did not meet inclusion/exclusion criteria.
Participants were recruited through Vanderbilt University-affiliated clinics and the greater Nashville, TN community.
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| ID | Title | Description |
|---|---|---|
| FG000 | Transdermal Nicotine | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 27, 2017 |
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| Placebo Transdermal Patch | Other | Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm. |
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| Baseline to 8 Weeks |
| FG001 | Placebo | 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 |
| COMPLETED | Number Completed |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Transdermal Nicotine | 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. |
| BG001 | Placebo | 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 |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Cancer Type | Count of Participants | Participants |
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| Cancer Stage | Count of Participants | Participants |
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| Cancer Treatment Received | Number | participants |
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| Current Endocrine Therapy | Count of Participants | Participants |
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| Post-Menopausal Status | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale | 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 | Posted | Mean | Standard Deviation | units on a scale | Baseline to 8-Weeks |
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| Secondary | Conners Continuous Performance Test | 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.* | Posted | Mean | Standard Deviation | ms | Baseline to 8 Weeks |
|
8-Weeks
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).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Transdermal Nicotine | 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. | 0 | 11 | 0 | 11 | 7 | 11 |
| EG001 | Placebo | 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 | 0 | 11 | 0 | 11 | 8 | 11 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin Irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Gastrointestinal | Gastrointestinal disorders | Systematic Assessment | Nausea |
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| Neurologic | General disorders | Systematic Assessment | Dizziness |
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| Mood | General disorders | Systematic Assessment | Irritability |
| |
| Insomnia | General disorders | Systematic Assessment | Insomnia |
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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.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Paul A. Newhouse | Vanderbilt University Medical Center | (615) 327-7009 | paul.newhouse@vumc.org |
| May 16, 2019 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D000084202 | Chemotherapy-Related Cognitive Impairment |
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D064420 | Drug-Related Side Effects and Adverse Reactions |
| D064419 | Chemically-Induced Disorders |
| D060825 | Cognitive Dysfunction |
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
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| ID | Term |
|---|---|
| D061485 | Tobacco Use Cessation Devices |
| ID | Term |
|---|---|
| D013812 | Therapeutics |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Non-Hodgekin's Lymphoma |
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| Ovarian Cancer |
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| Colon Cancer |
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| Stage II |
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| Stage III |
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| Stage IV |
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| Surgery |
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| Radiation |
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| No |
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| Post-Menopausal |
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| Visit 5 PCI Change from Baseline Score (8-Weeks) |
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| OG001 | Placebo | 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. |
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