Intellectual Impairment in Women With Breast Cancer

• ClinicalTrials.gov Identifier: NCT00896324
• Recruitment Status: Completed
• First Posted: May 11, 2009
• Last Update Posted: May 1, 2019
• Sponsor: Stanford University
• Information provided by (Responsible Party): Oxana Palesh, Stanford University

Study Description

Brief Summary:

RATIONALE: Breast cancer and its treatment may cause changes in a patient's ability to think, learn, and remember. Gathering information about a woman's genes, brain function, and personal history may help doctors learn more about the disease and plan the best treatment.

PURPOSE:

1. To determine changes in brain function that occur following breast cancer chemotherapy.
2. To gain further understanding of the individual differences in brain function changes and recovery based on demographic, medical and treatment variables.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Behavioral: Cognitive Rehabilitation; Behavioral: Active Neurofeedback Training; Behavioral: Neurofeedback Training (placebo / Sham)	Not Applicable

Detailed Description:

This study aims to determine some of the genetic, neurobiologic and demographic factors that are associated with cognitive outcome following breast cancer (BC). Additionally, it aims to test novel behavioral interventions designed to improve executive function skills following BC treatment.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Pre-chemotherapy participants are randomized between active neurofeedback, and a sham (placebo) neurofeedback.
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Health Services Research
• Official Title: Assessment and Treatment of Cognitive Deficits in Breast Cancer
• Actual Study Start Date: January 12, 2009
• Actual Primary Completion Date: June 2013
• Actual Study Completion Date: June 2013

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Cognitive Rehabilitation (Breast Cancer(BC) with chemotherapy); Cognitive rehabilitation is a very low-risk method of treatment for cognitive deficits that involves restoring impaired function and/or training the individual to compensate for the area of deficit. Subjects will complete a curriculum of cognitive exercises 30 minutes per day, 5 days per week for 6-weeks.	Behavioral: Cognitive Rehabilitation; The cognitive rehabilitation procedure will involve a curriculum of game-like cognitive exercises designed to facilitate graded practice of EF skills including attention, processing speed, mental flexibility, planning and logic. The exercises will be delivered to participants via a secure, password protected website created specifically for this study by the PI. Subjects will complete a curriculum of cognitive exercises 30 minutes per day, 5 days per week for 6-weeks.
Active Comparator: Active Neurofeedback (BC pre-chemotherapy); In active Neurofeedback session subjects will be trained to increase brain activation in regions associated with executive function (EF) function deficits (as determined by neuroimaging measures) by viewing their own brain activation in real-time. The "dose" will be 2-3 sessions, each lasting approximately 30 minutes.	Behavioral: Active Neurofeedback Training; Neurofeedback training is a type of biofeedback during which the subjects will be trained to improve cognitive function by implementing certain cognitive strategies while receiving feedback of their own brain activity. This is done using an infrared spectroscopy (NIRS) system. NIRS measurements will be performed using an ETG-4000 NIRS system (Hitachi Medical, Tokyo, Japan), at two wavelengths of near-infrared light (695 and 830 nm). Each participant will have 2 or 3 sessions, each lasting approximately 30 minutes.
Sham Comparator: Neurofeedback placebo (Sham) (BC pre-chemotherapy); Neurofeedback training: 2-3, 30 min training sessions. For the sham placebo group, fabricated real-time data will be provided to the subject as feedback information hence enabling the subject to view information identical to experimental subjects but without accurate data pertaining to their own brain activation. The technician will be blinded to the subject's treatment condition assignment.	Behavioral: Neurofeedback Training (placebo / Sham); Neurofeedback training: 2-3, 30 min training sessions. For the sham placebo group, fabricated real-time data will be provided to the subject as feedback information hence enabling the subject to view information identical to experimental subjects but without accurate data pertaining to their own brain activation. The technician will be blinded to the subject's treatment condition assignment.

Outcome Measures

Primary Outcome Measures :

1. Examine the effectiveness of a cognitive rehabilitation program for improving executive function (EF) deficits for preventing or lessening EF impairments in women with Breast Cancer [ Time Frame: 6 weeks ]
   Evaluation of efficacy of executive function (EF) will be done via Neuropsychological and Neuroimaging (using functional MRI) assessments. Measurements of executive function, memory, processing speed, attention, visual-spatial processing and language will be compared before and after 6 weeks of cognitive rehabilitation program. Neuropsychological assessment and neuroimaging assessment changes will be compared from baseline to post-assessment in the intervention groups. Mixed effects approach and reliable change index (RCI) will be used as a supplementary analysis to determine the change in cognitive testing scores from pre- to post-intervention.Specific neuroimaging data (e.g. prefrontal cortex volumes, hippocampal metabolite levels, whole brain white matter fractional anisotropy) will be correlated with neuropsychological testing scores.

Secondary Outcome Measures :

1. Examine the effectiveness of neurofeedback training program for preventing or reducing cognitive deficits in women with Breast Cancer [ Time Frame: up to 6 months ]
   Neurofeedback training test will be done on women with BC, prior to receiving adjuvant chemotherapy. For the sham placebo group, fabricated real-time data will be provided to the subject as feedback information. Prefrontal and parietal regions of interest will be measured by putting a nylon cap attached to 16 optode emitter/receiver pairs on each subject's head covering the bilateral frontal and parietal regions symmetrically. Measurements will be recorded every 0.1s. The pretask baseline will be determined
2. Evaluate diurnal cortisol levels on executive function outcome in women with Breast cancer [ Time Frame: 2 days ]
   Saliva collection for cortisol analysis will be done with women with BC/chemotherapy, women BC/ no chemotherapy and healthy women. Saliva samples for cortisol analysis will be collected from subjects on 2 consecutive days after the neuropsychological testing and MRI scan have been completed using SARSTEDT Salivettes. Cortisol analysis will be conducted using luminescence immunoassay. The cortisol slope of baseline days will be used as a measure of baseline cortisol level. Cortisol Levels will be correlated with cognitive testing scores.

Eligibility Criteria

• Ages Eligible for Study: 40 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

3.1.1 Primary, non-metastatic breast cancer

3.1.2 Newly diagnosed patients who have not yet begun treatment.

3.1.4 Female participants age 40-65 years of all ethnicities who speak fluent English will be recruited.

3.1.5 There are no life expectancy restrictions.

3.1.6 Karnofsky Performance Status 70% minimum. ECOG will not be employed.

3.1.7 There are no requirements for marrow function. The brain must be free from gross neuropathology and metastases in order to participate.

3.1.8 Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

3.2.1 History of cognitive, psychiatric or medical conditions prior or unrelated to cancer diagnosis and/or known to significantly impact assessments (e.g. premature birth, developmental delays, learning disabilities, severe psychiatric conditions, brain injury, stroke). Non-English speaking. Major sensory impairment (e.g. hearing loss, blindness) that would render assessments invalid. MRI contraindications (e.g. metallic implants or devices). Distant metastases. See also section 4.2.1.

3.2.2 Participants currently involved in studies specifically aimed at improving cognitive symptoms will be excluded.

3.2.3 Participants with significant co-morbid diseases known to significant impact neuropsychological function such as Alzheimer's or Parkinson's will be excluded.

3.2.4 There are no known risks for allergic reactions to any of the study procedures.

3.2.5 Participants taking certain medications that affect neuropsychological and/or brain function including Haldol, Aricept, Ritalin, etc. will be excluded. Most anti-depressants are acceptable. Some anti-anxiety medications may not be. Each case will be individually reviewed.

3.2.6 There are no other agent-specific exclusion criteria.

3.2.7 Pregnant individuals will be excluded as this is a contraindication for the 3 Tesla research MRI scanner employed by this study but not because of the treatment programs per se. Nursing individuals can enroll.

3.2.8 Patients who are HIV positive will be excluded given the known effects of this condition on cognitive function which would confound the effects of anti-cancer treatments on cognitive outcome.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Oxana Palesh; Stanford University

More Information

• Responsible Party: Oxana Palesh, Assistant Professor of Psychiatry and Behavioral Sciences, Stanford University
• ClinicalTrials.gov Identifier: NCT00896324
• Obsolete Identifiers: NCT00866931
• Other Study ID Numbers: IRB-14623 part 1; SU-04062009-2139 ( Other Identifier: Stanford University ); BRS0002 ( Other Identifier: OnCore )
• First Posted: May 11, 2009
• Last Update Posted: May 1, 2019
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Oxana Palesh, Stanford University:

Quality of life

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases