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

NCT02312934 | Completed Phase 2 Results DMC

• 1 other identifier: 141584
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• Conners Continuous Performance Test

  Baseline to 8 Weeks

Study Arms (2)

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

Drug: Transdermal nicotine

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

Other: Placebo Transdermal Patch

Interventions

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.

Transdermal Nicotine

Placebo Transdermal Patch OTHER

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

Placebo

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Center for Cognitive Medicine at Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Chemotherapy-Related Cognitive Impairment; Breast Neoplasms

Interventions

Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Drug-Related Side Effects and Adverse Reactions; Chemically-Induced Disorders; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Therapeutics

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Paul A. Newhouse
• Organization: Vanderbilt University Medical Center

paul.newhouse@vumc.org

(615) 327-7009

Study Officials

• Paul A Newhouse, M.D.

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry, Pharmacology, and Medicine

Study Record Dates

• First Submitted: December 5, 2014
• First Posted: December 9, 2014
• Study Start: August 1, 2015
• Primary Completion: May 1, 2018
• Study Completion: May 1, 2018
• Last Updated: January 21, 2020
• Results First Posted: January 21, 2020

Record last verified: 2020-01

Locations

US (1)