Chemotherapy-Related Changes in Neurocognitive Function and Symptoms in Colorectal Cancer Patients: A Pilot Study

September 27, 2023 updated by: University of Nebraska
Cancer treatments have successfully improved cancer outcomes but frequently negatively impact quality of life in cancer survivors. In particular, chemotherapy (CTX) has been associated with impaired cognitive abilities such as concentration and memory. The goal is to investigate the neural mechanisms of chemotherapy-related cognitive impairment (CRCI) using an interdisciplinary translational approach. Previous research in this area lacks diversity in studied cancer populations and treatments focusing primarily on breast cancer and provides limited understanding of how CRCI emerges from changes in neural structure, function, and connectivity. To overcome these limitations, this feasibility/pilot study aims to investigate CRCI in patients with colorectal cancer (CRC).

Study Overview

Status

Completed

Conditions

Detailed Description

A growing public health and oncology nursing concern is the likelihood of colorectal cancer (CRC) survivors experiencing decline in long-term physical and mental functional status following cancer diagnosis and treatment. Prior to receiving treatment, cognitive impairment in processing speed, spatial working memory, and verbal memory has been noted in 45% of CRC patients relative to 15% of healthy controls (HC). Following adjuvant chemotherapy, cognitive function is more impaired in CRC patients who received chemotherapy (Ctx+ group) compared to CRC patients not receiving chemotherapy (Ctx- group) and HC participants. These studies show: (1) CRC patients are at a high risk for cognitive impairment and (2) Ctx+ patients are more likely to decline in cognitive function during treatment. These cancer and chemotherapy-related changes in cognitive function have been associated with several quality of life factors, including physiological and concurrent symptoms, and physical and mental functional status. In contrast, the neural mechanisms of cognitive impairment in CRC patients is related to changes in the Executive Function Network (EFN). The EFN promotes long-range communication between frontal and parietal cortical regions, and is associated with attentional control processes. The empirical goals studying CRC patients are two-fold: (1) Develop a core set of cognitive function, event related potential (ERP) measures from electroencephalogram (EEG), and resting-state functional magnetic resonance imaging (rsfMRI) measures to elucidate the relationship between impaired attentional control and EFN dysfunction and (2) Increase understanding of the link between neurocognitive impairment with concurrent symptom severity and impact on functioning. The investigators propose a longitudinal, prospective cohort pilot design to study post-operative CRC patients scheduled to begin adjuvant chemotherapy (Ctx+ group). Comparison groups will include post-operative CRC patients not receiving chemotherapy (Ctx- group) and healthy controls demographically matched to Ctx+ participants (HC group). All participants (N=60; 20 per group) will complete an additional 1-hour study visits at baseline and 24-weeks to collect rsfMRI measurements Ctx+ patients will complete baseline assessment after surgery but before starting chemotherapy, CTx- patients will complete baseline assessments 4-6 weeks after surgery and HC after matched and consented.

Study Type

Observational

Enrollment (Actual)

40

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
    • Nebraska
      • Omaha, Nebraska, United States, 68918
        • University of Nerbaska Medical Center

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

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

CRC Diagnosis:

Worse prognosis includes presentation with complete colon obstruction, perforation, T4 tumor fewer than 12 lymph nodes examined, elevated CEA levels pre-or post-surgery, positive margins, and peri-neural, lymphatic or venous invasion. Molecular markers also correlate with the aggressiveness of colon cancer.

Description

Inclusion Criteria:

CRC adenocarcinoma patients:

  • Stage II/IV patients receiving adjuvant CTX (Ctx+ group)
  • Stage I/III patients not receiving CTX (Ctx- group)
  • Normal or corrected to normal vision (corrected far visual acuity of 20/50 or better)

For demographically-matched healthy controls (HC group)

  • Matched to patient receiving CTX on demographics: age (plus or minus 5 years, gender, race, menopausal status, and education (plus or minus 2 years)
  • Normal or corrected-to-normal vision (corrected far visual acuity of 20/50 or better)

Exclusion Criteria:

CRC patients:

Cancer diagnosis/treatment in last 3 yrs. in addition to CRC (exceptionpatients with localized skin cancer) Prior chemotherapy within 1 year for CRC Cognitive impairment (MMSE score < 25) prior to baseline assessment

Demographically-matched healthy controls:

CRC cancer diagnosis All exclusion criteria for CRC patients.

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

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
CRC patients (Ctx+ group)
Postoperative CRC patients scheduled to begin CTX
CRC patients (CT- group)
Postoperative CRC patients who do not receive CTX
Healthy control group
Study participants that are demographically matched to CRC study patients and meet all inclusion criteria

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from Trails A baseline at 12 weeks and 24 weeks (Specific Aim 1)
Time Frame: Change from baseline to 12 and 24 weeks
Neurocognitive measure of processing speed; Completion time (milliseconds), where longer completion times are interpreted as slower processing speed
Change from baseline to 12 and 24 weeks
Change from Trails B baseline at 12 weeks and 24 weeks (Specific Aim 1)
Time Frame: Change from baseline to 12 weeks and 24 weeks
Neurocognitive measure of executive functioning; Completion time (milliseconds) where larger differences in completion time are interpreted as slower executive functioning processes
Change from baseline to 12 weeks and 24 weeks
Change from Symbol Digit Modalities baseline at 12 weeks and 24 weeks (Specific Aim 1)
Time Frame: Change from baseline to 12 weeks and 24 weeks
Neurocognitive measure of psychomotor speed; Total correct complete, where greater number completed is interpreted as faster psychomotor speed
Change from baseline to 12 weeks and 24 weeks
Change from Stroop baseline at 12 weeks and 24 weeks (Specific Aim 1)
Time Frame: Change from baseline to 12 weeks and 24 weeks
Neurocognitive measure of inhibitory control; Total number completed, where greater number completed is interpreted as better inhibitory control.Interference scores are obtained to estimate inhibitory control, where more negative values are interpreted as lower inhibitory control (estimated by subtracting expected performance from observed performance in color-word condition)
Change from baseline to 12 weeks and 24 weeks
Change from Auditory Verbal Learning Task baseline at 12 weeks and 24 weeks (Specific Aim 1)
Time Frame: Change from Baseline to 12 and 24 weeks
Neurocognitive measure of verbal memory; Total number recalled (immediate), where greater number immediately recalled is interpreted as better verbal short-term memory. Total number recalled (delayed), where greater number recall following delay is interpreted as better verbal long-term memory
Change from Baseline to 12 and 24 weeks
Change from Visual Search Performance baseline at 12 weeks and 24 weeks (Specific Aim IIa)
Time Frame: Change from baseline to 12 and 24 weeks
Measure of Response time (milliseconds), where longer response times are interpreted as slower processing speed and lower inhibitory control.
Change from baseline to 12 and 24 weeks
Change from Change Detection Performance baseline at 12 weeks and 24 weeks (Specific Aim IIa)
Time Frame: Change from baseline to 12 and 24 weeks
Measure of response accuracy, where larger response accuracies are interpreted as larger working memory capacity and higher inhibitory control.
Change from baseline to 12 and 24 weeks
Change from N2pc amplitude during visual search baseline at 12 weeks and 24 weeks (Specific Aim IIa)
Time Frame: Change from baseline to 12 and 24 weeks
Measure of attentional control. Larger amplitudes are interpreted as more resources allocated towards stimulus selection and poor attentional control
Change from baseline to 12 and 24 weeks
Change from Contralateral delay activity (CDA) amplitude change during task performance baseline at 12 weeks and 24 weeks (Specific Aim IIa)
Time Frame: Change from baseline to 12 and 24 weeks
Measure of working memory storage. Where larger amplitudes are interpreted as more resources allocated towards working memory storage.
Change from baseline to 12 and 24 weeks
Change from MRI white matter volume baseline at 12 weeks and 24 weeks (Specific Aim IIb)
Time Frame: Change from baseline to 6 months (only CTx+ group)
Measure of white matter volume within executive function network
Change from baseline to 6 months (only CTx+ group)
Change from MRI Grey matter volume baseline at 12 weeks and 24 weeks (Specific Aim IIb)
Time Frame: Change from baseline to 6 months (only CTx+ group)
Measure of grey matter volume within executive function network
Change from baseline to 6 months (only CTx+ group)
Change from Executive Functional Network functional connectivity baseline at 12 weeks and 24 weeks (Specific Aim IIb)
Time Frame: Change from baseline to 6 months (only CTx+ group)
EFN function
Change from baseline to 6 months (only CTx+ group)
Change from M.D. Anderson Symptom Inventory-Gastro-Intestinal (MDASI-GI) baseline at 12 weeks and 24 weeks(Specific Aim III)
Time Frame: Change from baseline to 12 weeks and 24 weeks
Measures co-occurring symptom severity and interference with function
Change from baseline to 12 weeks and 24 weeks
Change from Research And Development (RAND) Short Form-12 (SF-12) from baseline to 12 and 24 weeks (Specific Aim III)
Time Frame: Change from baseline to 12 weeks and 24 weeks
Measures physical and mental functional status
Change from baseline to 12 weeks and 24 weeks
Change from Functional Assessment of Cancer Therapy- Cognitive (FACT-COG) at baseline to 12 and 24 weeks (Specific Aim III)
Time Frame: Change from baseline to12 weeks and 24 weeks
Self-perceives cognitive function
Change from baseline to12 weeks and 24 weeks
Change from Beck Depression Inventory (BDI) from baseline to 12 and 24 weeks (Specific Aim III)
Time Frame: Change from baseline to 12 and 24 weeks
Assesses depressive symptoms
Change from baseline to 12 and 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from logMAR visual acuity baseline at 12 weeks and 24 weeks
Time Frame: Change from baseline to 12 and 24 weeks
Measures visual acuity. Relatively lower logMAR values are interpreted as better visual acuity (estimated as log transformed estimate of visual acuity with respect to deviation from standard 20/20)
Change from baseline to 12 and 24 weeks
Change from logMAR contrast sensitivity baseline at 12 weeks and 24 weeks
Time Frame: Change from baseline to 12 and 24 weeks
Measures contrast sensitivity. Relatively lower logMAR values are interpreted as better contrast sensitivity.
Change from baseline to 12 and 24 weeks
Change from Frequency Doubling Technology baseline at 12 weeks and 24 weeks
Time Frame: Change from baseline to 12 and 24 weeks
Measures visual field loss. A binary (yes/no) variable where presence of visual field defect is coded as evidence of visual field loss
Change from baseline to 12 and 24 weeks
Change from Optical Coherence Tomography baseline at 12 weeks and 24 weeks
Time Frame: Change from baseline to 12 and 24 weeks
Measure of retinal nerve fiber layer (RNFL) thickness
Change from baseline to 12 and 24 weeks

Collaborators and Investigators

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

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: Ann M Berger, PhD, University of Nebraska

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 (Actual)

January 22, 2018

Primary Completion (Actual)

November 25, 2020

Study Completion (Actual)

November 25, 2020

Study Registration Dates

First Submitted

July 5, 2018

First Submitted That Met QC Criteria

September 20, 2018

First Posted (Actual)

September 25, 2018

Study Record Updates

Last Update Posted (Actual)

September 29, 2023

Last Update Submitted That Met QC Criteria

September 27, 2023

Last Verified

September 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0228-17-EP

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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