Chemotherapy-Induced Cognitive Impairment

Cognitive Symptoms Clinical Trial

— CICI  

Official title:

The Neurobiology of Chemotherapy-Induced Cognitive Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01578083
• Other study ID #: 201203045
• Status: Completed
• Phase: N/A
• First received: April 12, 2012
• Last updated: February 25, 2013
• Start date: April 2012
• Est. completion date: December 2012

Study information

• Verified date: April 2012
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: December 2012
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 70 Years

Eligibility

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 Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Cognition Disorders
• Cognitive Symptoms
• Neurobehavioral Manifestations

Locations

Country	Name	City	State
United States	Washington University School of Medicine	St. Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
Jay F. Piccirillo, MD	Barnes-Jewish Hospital, Washington University Siteman Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in fractional anisotropy (FA) in one or more white matter tracts.	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.	No
Secondary	rs-fcMRI-defined disruptions in cognitive cortical networks	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.	No
Secondary	Changes in Mean Diffusivity (MD) in one or more white matter tracks	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.	No