Chemotherapy-Induced Cognitive Impairment (CICI)

February 25, 2013 updated by: Jay F. Piccirillo, MD

The Neurobiology of Chemotherapy-Induced Cognitive Impairment

The investigators overall research hypothesis is that systemic chemotherapy induces structural changes in the white matter of the brain as demonstrated with Diffusion Tensor Imaging (DTI) and functional changes in well-defined cortical neural networks as demonstrated by resting-state functional connectivity MRI (rs-fcMRI). The investigators believe these structural and functional changes are responsible for the cognitive symptoms associated with chemotherapy-induced cognitive impairment (CICI).

The Specific Aim for this study is:

To assess the impact of chemotherapy on structural white matter as defined by DTI and functional cognitive networks as defined by rs-fcMRI by comparing a sample of breast cancer survivors with self-reported CICI to breast cancer survivors without CICI.

Hypothesis: Post-chemotherapy breast cancer patients with self-reported CICI will have abnormal structural connections characterized by DTI-defined disruptions in fractional anisotropy (FA) and mean diffusivity (MD) and abnormal functional connectivity characterized by rs-fcMRI-defined disruptions in cognitive networks when compared to patients without self-reported CICI.

Study Overview

Status

Completed

Conditions

Detailed Description

Chemotherapy has been linked to cognitive impairments among breast cancer patients, especially in the domains of executive function (planning and problem solving), attention, learning, and information processing. The etiology of these chemotherapy-associated impairments remains unknown, although recent neuroimaging studies suggest that disruption of white matter integrity may play a role. With continued use of chemotherapy in breast cancer patients, this study's novel use of functional neuroimaging will be significant to better inform practitioners and patients of potential consequences to anticipate and serve as a starting point in the development of therapeutic interventions.

Study Type

Observational

Enrollment (Actual)

28

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
    • Missouri
      • St. Louis, Missouri, United States, 63110
        • Washington University School of Medicine

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 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

Breast cancer surviviors from Washington University's Siteman Cancer Center and from community at large.

Description

Inclusion Criteria:

  • Inclusion Criteria (Phase I and II):

    • Participants must be females between 35 and 70 years of age.
    • Participants must have been diagnosed with breast cancer and completed chemotherapy,within the preceding 2 years.
    • Participants must have completed their intended full course of chemotherapy regimen at least 30 days prior to participation.
    • Participants must have been diagnosed with invasive ductal or lobular BrCa Stages I, II, or III (American Joint Committee on Cancer (AJCC) staging manual, 7th edition, 2010).

Inclusion Criteria (Phase II)

  • Participants must be able to read, write, and speak English fluently.
  • Participants must be able to provide a valid informed consent.
  • Participants must have a life expectancy of greater than 6 months at the time they are approached for enrollment.
  • Cases - Those who self-report CICI and are in the 75th percentile of scores on the Cognitive Failures Questionnaire (CFQ) and have a global rating of cognition response of "Extremely Affected" or "Strongly Affected"
  • Controls - Those whose CFQ scores are in the lowest 25th percentile and who report that their daily life is not affected by cognitive impairment. Controls will be selected so that they are age (within 5 years)-matched to a Case.

Exclusion Criteria:

  • • Participants with prior cancer diagnoses of other sites with evidence of active disease within the past year.

    • Participants who have received skull-base radiation treatment within the past year for any reason. Skull-base radiation may contribute to the symptoms of CICI.
    • Participants with active diagnoses of any acute or chronic brain-related neurological conditions that can alter normal brain anatomy or function, including Parkinson's disease, Multiple Sclerosis, Alzheimer's Disease, cerebral infarcts, , history of brain tumor(s), epilepsy, or dementia.
    • Must not have a history of traumatic brain injury (loss of consciousness for > 15 min.)
    • Participants with implanted metal objects not compatible with MRI, electrodes, pacemakers, intracardiac lines, or medication pumps.
    • Participants who weigh over 350 pounds (weight limit on MRI machine).
    • Participants with a history of claustrophobia that will preclude undergoing MRI.
    • Participants with an inability to lie flat for MRI.
    • Any medical condition the PI determines would render the study unsafe or not in the best interest of the patient.

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

Cohorts and Interventions

Group / Cohort
Cognitive Impairment
With self-report cognitive impairment.
No Cognitive Impairment
Without self-report cognitive impairment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in fractional anisotropy (FA) in one or more white matter tracts.
Time Frame: post-chemotherapy. One time measure within one year of final dose of chemotherapy.
As compared with the controls, the breast cancer patients will show decreased fractional anisotropy (FA) in the frontal and temporal white matter (WM) tracts and.
post-chemotherapy. One time measure within one year of final dose of chemotherapy.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rs-fcMRI-defined disruptions in cognitive cortical networks
Time Frame: post-chemotherapy: post-chemotherapy. One time measure within one year of final dose of chemotherapy.
As compared with the controls, the breast cancer patients will show decreased functional integrity of the default mode network [DMN], associated with memory; the dorsal and ventral attention networks [DAN/VAN], involved in attention; and the Cognitive/Control network, involved in executive decision-making
post-chemotherapy: post-chemotherapy. One time measure within one year of final dose of chemotherapy.
Changes in Mean Diffusivity (MD) in one or more white matter tracks
Time Frame: Post Chemotherapy: post-chemotherapy. One time measure within one year of final dose of chemotherapy.
As compared with the controls, the breast cancer patients will show increased mean diffusivity (MD) in frontal White Matter (WM).
Post Chemotherapy: post-chemotherapy. One time measure within one year of final dose of chemotherapy.

Collaborators and Investigators

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

Sponsor

Jay F. Piccirillo, MD

Collaborators

Barnes-Jewish Hospital
Washington University Siteman Cancer Center

Investigators

  • Principal Investigator: Jay F. Piccirillo, MD, Washington University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

April 1, 2012

Primary Completion (Actual)

December 1, 2012

Study Completion (Actual)

December 1, 2012

Study Registration Dates

First Submitted

April 12, 2012

First Submitted That Met QC Criteria

April 13, 2012

First Posted (Estimate)

April 16, 2012

Study Record Updates

Last Update Posted (Estimate)

February 26, 2013

Last Update Submitted That Met QC Criteria

February 25, 2013

Last Verified

April 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 201203045

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.

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