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

January 10, 2020 updated by: Paul Newhouse, Vanderbilt University Medical Center
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Nashville, Tennessee, United States, 37212
        • Center for Cognitive Medicine at Vanderbilt University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: 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.
Placebo Comparator: 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
Other: Placebo Transdermal Patch
Matching transdermal placebo patches will be used. Participants will follow the same titration schedule as the transdermal nicotine arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) PCI Scale
Time Frame: Baseline to 8-Weeks

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Conners Continuous Performance Test
Time Frame: Baseline to 8 Weeks

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.*
Baseline to 8 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Vanderbilt University Medical Center

Investigators

  • Principal Investigator: Paul A Newhouse, M.D., Vanderbilt University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2015

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

May 1, 2018

Study Registration Dates

First Submitted

December 5, 2014

First Submitted That Met QC Criteria

December 8, 2014

First Posted (Estimate)

December 9, 2014

Study Record Updates

Last Update Posted (Actual)

January 21, 2020

Last Update Submitted That Met QC Criteria

January 10, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 141584

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Transdermal nicotine

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malta

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe