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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02312934
Recruitment Status : Completed
First Posted : December 9, 2014
Results First Posted : January 21, 2020
Last Update Posted : January 21, 2020
Sponsor:
Information provided by (Responsible Party):
Paul Newhouse, Vanderbilt University Medical Center

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.

Condition or disease Intervention/treatment Phase
Chemo Brain Chemotherapy-related Cognitive Impairment Chemo Fog Breast Cancer Chemobrain Drug: Transdermal nicotine Other: Placebo Transdermal Patch Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Nicotinic Treatment of Post-Chemotherapy Subjective Cognitive Impairment: A Pilot Study
Actual Study Start Date : August 2015
Actual Primary Completion Date : May 2018
Actual Study Completion Date : May 2018

Resource links provided by the National Library of Medicine


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.




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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.*




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   35 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02312934


Locations
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United States, Tennessee
Center for Cognitive Medicine at Vanderbilt University
Nashville, Tennessee, United States, 37212
Sponsors and Collaborators
Vanderbilt University Medical Center
Investigators
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Principal Investigator: Paul A Newhouse, M.D. Vanderbilt University
  Study Documents (Full-Text)

Documents provided by Paul Newhouse, Vanderbilt University Medical Center:
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Responsible Party: Paul Newhouse, Professor of Psychiatry, Pharmacology, and Medicine, Vanderbilt University Medical Center
ClinicalTrials.gov Identifier: NCT02312934    
Other Study ID Numbers: 141584
First Posted: December 9, 2014    Key Record Dates
Results First Posted: January 21, 2020
Last Update Posted: January 21, 2020
Last Verified: January 2020
Keywords provided by Paul Newhouse, Vanderbilt University Medical Center:
Chemo brain
Chemotherapy-related cognitive impairment
CRCI
Breast cancer
Chemo fog
Nicotine
Transdermal nicotine
Additional relevant MeSH terms:
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Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action