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

Primary Purpose

Chemo Brain, Chemotherapy-related Cognitive Impairment, Chemo Fog

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Transdermal nicotine
Placebo Transdermal Patch
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chemo Brain focused on measuring Chemo brain, Chemotherapy-related cognitive impairment, CRCI, Breast cancer, Chemo fog, Nicotine, Transdermal nicotine

Eligibility Criteria

35 Years - 80 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • Center for Cognitive Medicine at Vanderbilt University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Transdermal Nicotine

Placebo

Arm Description

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.*

Full Information

First Posted
December 5, 2014
Last Updated
January 10, 2020
Sponsor
Vanderbilt University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT02312934
Brief Title
Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study
Official Title
Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
August 2015 (Actual)
Primary Completion Date
May 2018 (Actual)
Study Completion Date
May 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemo Brain, Chemotherapy-related Cognitive Impairment, Chemo Fog, Breast Cancer, Chemobrain
Keywords
Chemo brain, Chemotherapy-related cognitive impairment, CRCI, Breast cancer, Chemo fog, Nicotine, Transdermal nicotine

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Transdermal Nicotine
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Transdermal nicotine
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Placebo Transdermal Patch
Intervention Description
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.
Primary Outcome Measure Information:
Title
Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale
Description
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
Time Frame
Baseline to 8-Weeks
Secondary Outcome Measure Information:
Title
Conners Continuous Performance Test
Description
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.*
Time Frame
Baseline to 8 Weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: All participants will: Be between 35 and 80 years of age, Have been diagnosed with noninvasive or invasive (Stage 1, 2, or 3A) breast cancer, Have undergone treatment with systemic chemotherapy within the last 1-5 years, Endorse persistent CRCI subjective complaints, Be non-smokers (no nicotine use within the last 5 years), Have no active cardiac, neurologic, or psychiatric illness, and Fluent in and able to read English. Exclusion Criteria: Participants will be excluded for: Any active neurologic and/or psychiatric disease, history of significant head trauma followed by persistent neurologic deficits, or known structural brain abnormalities, 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), Any history of alcohol or substance abuse or dependence within the past 2 years (DSM-5 criteria), 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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul A Newhouse, M.D.
Organizational Affiliation
Vanderbilt University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Center for Cognitive Medicine at Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37212
Country
United States

12. IPD Sharing Statement

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

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