Chemobrain: Electrophysiological Biomarkers of Chemotherapy-related Cognitive Impairment and Recovery
Study Details
Study Description
Brief Summary
Broadly speaking, the goal of this study is to better understand the influence of chemotherapy treatment on the cognitive and neural mechanisms underlying human behavior. Extant literature lacks diversity in studied cancer populations and treatment protocols, and provides limited understanding of the cognitive abilities that are impaired by chemotherapy. To overcome these limitations, this study will employ a sophisticated battery of tests on an understudied cancer population. Eligible participants will either be patients diagnosed with hematological malignancy (HM) or demographically matched healthy control patients.
After HM diagnosis and treatment protocols have been established, patients will be inducted into the longitudinal study comprised of three visits: 1) after diagnosis but prior to chemotherapy treatment (baseline), 2) after one treatment cycle (one month post-baseline), and 3) after three treatment cycles (three months post-baseline). Patients will undergo a test battery designed to measure specific behavioral and neural mechanisms of attention; tests will either be computer-based cognitive tasks or simulated driving tests that immerse patients into virtual driving scenarios. During each test, EEG will be concurrently measured through non-invasive scalp electrophysiology recordings; EEG recordings will reveal underlying neural mechanisms affected by chemotherapy. Additionally, neuropsychological tests of vision, attention, and memory will be administered, as well as questionnaires to evaluate health, mobility, and life space. Finally, blood samples will be collected to examine levels of circulating inflammation-specific proteins typically present in cancer patients. This study will allow us to better understand the mechanisms through which chemotherapy influences cognitive performance. Results from this study will influence the administration of chemotherapy treatments so that patients can continue to receive the highest medical care while maintaining optimal cognitive abilities and quality of life.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
|
Detailed Description
The broad goal of this research project is to develop a core set of biomarkers for chemotherapy-related cognitive impairment (or chemobrain). Clinical studies have documented mild cognitive impairment in chemotherapy patients most frequently within the domains of attention and memory, though impairments have been observed across a broad range of cognitive abilities. In addition, neuroimaging studies have demonstrated chemotherapy-related structural and functional changes in distributed cortical areas, including regions of the fronto-parietal attention network. While these studies suggest chemotherapy treatment negatively impacts patient health and cognitive function, it remains unclear how chemotherapy affects neural mechanisms of cognitive abilities. Current literature is limited in four major ways: (1) most research has focused on breast cancer populations, providing little insight into impact of tumor type, (2) few studies have examined the parametric effects of chemotherapy toxicity, (3) neuropsychological exams provide weak resolution of specific cognitive functions, and (4) neural factors associated with cognitive impairment are difficult to dissociate from non-neural (e.g. psychosocial) factors. To overcome these central limitations, the investigators propose a one-year longitudinal study that aims to systematically examine the influence of cancer stage and treatment toxicity on mild cognitive impairment observed in hematological malignancy (HM) patients by implementing a core battery of behavioral and neural measures of attention.
Our specific aims (SA) are to:
SA1: Quantify chemotherapy-related impairments of attention-specific processes in HM patients.
H1a: No difference in behavioral measures of attention will be observed across HM groups prior to treatment, and HM groups will perform worse than healthy controls.
H1b: Exposure to chemotherapy will predict behavioral impairments of attention, and the magnitude of impairment will be linked with treatment toxicity.
SA2: Quantify electrophysiological measures of attention-specific processes and determine the link between chemotherapy-related impairments in neural activity and cognitive ability.
H2a: No difference in electrophysiological measures of attention will be observed across HM and healthy control groups prior to treatment.
H2b: Exposure to chemotherapy will predict functional impairments in electrophysiological measures of attention, and the magnitude of impairment will be linked with treatment toxicity.
H2c: Chemotherapy-related impairment in neural measures of attention will be predicted by concurrent impairments in behavioral measures of attention (as in H1b).
SA3: Implement controlled simulations of on-road driving scenarios that probe specific attention processes to determine the impact of chemotherapy on complex real-world behavior.
H3a: No difference in driving performance will be observed across HM groups prior to treatment, and driving performance will be better in healthy controls compared to HM patients.
H3b: Exposure to chemotherapy will predict greater impairment in simulated driving performance, and the magnitude of impairment will be linked with treatment toxicity.
H3c: Impairments in behavioral (as in H1a) and neural measures (as in H2a) of attention will predict greater impairment in simulated on-road driving performance.
Our empirical approach will allow us to more rigorously study the neural mechanisms of chemotherapy-related cognitive impairment. The current proposal aims to extend previous research by longitudinally investigating an understudied cancer population whose constituents are assigned to a treatment group at diagnosis, thus providing sufficient experimental control for examining parametric effects of cancer burden and treatment toxicity on specific mechanisms of attention. Results obtained from this study will be critical to understanding risk factors associated with chemotherapy, which will allow clinicians to make informed treatment recommendations in order to reduce the likelihood of cognitive impairment and maintain the highest quality of life possible for the ever-increasing cancer survivor population.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| HM - Chemotherapy Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. |
|
| HM - No Chemotherapy Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. |
|
| Healthy Controls Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
Outcome Measures
Primary Outcome Measures
- Change From Baseline Capture Task Performance at 1- and 3- Months [Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction]
Response time - measured as the time required to respond to a target hidden among distractor items - is the primary outcome measure of the capture task. Proportional response time was calculated by subtracting mean response time in the neutral condition from response time in the capture condition, and dividing that number by the standard deviation of response time across conditions. Changes in proportional response time across study visits is reported. Positive values correspond to an increase in response time and negative values correspond to a decrease in response time.
- Change From Baseline N2pc Amplitude at 1- and 3- Months [Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction]
Electrophysiological component that measures allocation of attentional resources
- Change From Baseline Filter Task Performance at 1- and 3- Months [Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction]
Response accuracy - measured as the proportion of correct trials - is the primary outcome measure of the filter task. Changes in response accuracy were calculated by subtracting response accuracy at 1-month and 3-months from baseline response accuracy. Positive values correspond to an increase in accuracy and negative values correspond to a decline in accuracy.
- Change From Baseline CDA Amplitude at 1- and 3- Months [Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction]
Electrophysiological component that measures online storage load
Eligibility Criteria
Criteria
Inclusion criteria:
-
HM diagnosis
-
scheduled to receive treatment based on risk classification
-
between 19 to 80 years of age-
-
normal or corrected-to-normal vision
-
matched to HM patient demographics (healthy controls)
Exclusion criteria:
-
non-HM non-cutaneous cancer diagnosis (patients with localized skin cancer may not be excluded)
-
prior radiation or chemotherapy treatment
-
HM cancer diagnosis (healthy controls)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Nebraska Medical Center | Omaha | Nebraska | United States | 68132 |
Sponsors and Collaborators
- University of Nebraska
Investigators
None specified.Study Documents (Full-Text)
More Information
Publications
None provided.- 137-16-FB
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls |
|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
| Period Title: Overall Study | |||
| STARTED | 15 | 15 | 15 |
| COMPLETED | 8 | 10 | 12 |
| NOT COMPLETED | 7 | 5 | 3 |
Baseline Characteristics
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls | Total |
|---|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria | Total of all reporting groups |
| Overall Participants | 15 | 15 | 15 | 45 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
59.3
(15.2)
|
63.2
(10.9)
|
60.0
(16.5)
|
60.6
(14.5)
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
7
46.7%
|
9
60%
|
8
53.3%
|
24
53.3%
|
| Male |
8
53.3%
|
6
40%
|
7
46.7%
|
21
46.7%
|
| Race (NIH/OMB) (Count of Participants) | ||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
1
6.7%
|
0
0%
|
1
2.2%
|
| White |
15
100%
|
14
93.3%
|
15
100%
|
44
97.8%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | ||||
| United States |
15
100%
|
15
100%
|
15
100%
|
45
100%
|
Outcome Measures
| Title | Change From Baseline Capture Task Performance at 1- and 3- Months |
|---|---|
| Description | Response time - measured as the time required to respond to a target hidden among distractor items - is the primary outcome measure of the capture task. Proportional response time was calculated by subtracting mean response time in the neutral condition from response time in the capture condition, and dividing that number by the standard deviation of response time across conditions. Changes in proportional response time across study visits is reported. Positive values correspond to an increase in response time and negative values correspond to a decrease in response time. |
| Time Frame | Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed differed between rows due to participant dropout from Month-1 to Month-3. Differences in number analyzed and numbers in the Participant Flow module were due to patient dropout and either: (1) a minority of patients requesting not to complete testing; or (2) difficulties with electrophysiology or stimulus presentation equipment. |
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls |
|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
| Measure Participants | 8 | 11 | 12 |
| Change at 1-Month |
.103
(.223)
|
-.039
(.190)
|
.066
(.201)
|
| Change at 3-Month |
.067
(.113)
|
-.002
(.191)
|
-.084
(.165)
|
| Title | Change From Baseline N2pc Amplitude at 1- and 3- Months |
|---|---|
| Description | Electrophysiological component that measures allocation of attentional resources |
| Time Frame | Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| Differences in number analyzed and numbers in the Participant Flow module were due to patient dropout and either: (1) a minority of patients requesting not to complete testing; or (2) difficulties with electrophysiology or stimulus presentation equipment. |
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls |
|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
| Measure Participants | 7 | 10 | 11 |
| Change at 1-Month |
.47
(.77)
|
-.02
(.55)
|
-.34
(.54)
|
| Change at 3-Month |
.41
(1.00)
|
.36
(.96)
|
-.63
(.60)
|
| Title | Change From Baseline Filter Task Performance at 1- and 3- Months |
|---|---|
| Description | Response accuracy - measured as the proportion of correct trials - is the primary outcome measure of the filter task. Changes in response accuracy were calculated by subtracting response accuracy at 1-month and 3-months from baseline response accuracy. Positive values correspond to an increase in accuracy and negative values correspond to a decline in accuracy. |
| Time Frame | Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed differed between rows due to participant dropout from Month-1 to Month-3. Differences in number analyzed and numbers in the Participant Flow module were due to patient dropout and either: (1) a minority of patients requesting not to complete testing; or (2) difficulties with electrophysiology or stimulus presentation equipment. |
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls |
|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
| Measure Participants | 8 | 11 | 11 |
| Change at 1-Month |
-.013
(.04)
|
.011
(.027)
|
-.004
(.034)
|
| Change at 3-Month |
.002
(.031)
|
-.006
(.025)
|
-.006
(.028)
|
| Title | Change From Baseline CDA Amplitude at 1- and 3- Months |
|---|---|
| Description | Electrophysiological component that measures online storage load |
| Time Frame | Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction |
Outcome Measure Data
| Analysis Population Description |
|---|
| The number analyzed differed between rows due to participant dropout from Month-1 to Month-3. Differences in number analyzed and numbers in the Participant Flow module were due to patient dropout and either: (1) a minority of patients requesting not to complete testing; or (2) difficulties with electrophysiology or stimulus presentation equipment. |
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls |
|---|---|---|---|
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria |
| Measure Participants | 7 | 9 | 11 |
| Change at 1-Month |
.30
(.29)
|
-.22
(.91)
|
-.09
(.55)
|
| Change at 3-Month |
-.34
(.43)
|
-.10
(.87)
|
-.27
(.77)
|
Adverse Events
| Time Frame | Adverse events were monitored through study completion for each study participant. | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | This is a minimal risk study. To minimize risk, research personnel will frequently check in during all aspects of the protocol to ensure participant feels safe and comfortable. Breaks will be built into behavioral testing protocols, patients will be asked if they are experiencing any discomfort during the electrophysiological outfitting procedure, and patients will be guided through the simulator adaptation procedure to ensure that risk of nausea is minimized. | |||||
| Arm/Group Title | HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls | |||
| Arm/Group Description | Study patients diagnosed with HM that are scheduled to receive chemotherapy treatment. | Study patients diagnosed with HM that are scheduled to receive non-chemotherapy treatment options. | Study participants that are demographically matched to HM study patients and meet all inclusion criteria | |||
All Cause Mortality |
||||||
| HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | |||
Serious Adverse Events |
||||||
| HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| HM - Chemotherapy | HM - No Chemotherapy | Healthy Controls | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) | |||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. David Anderson |
|---|---|
| Organization | University of Nebraska Medical Center |
| Phone | 402-559-6870 |
| david.anderson@unmc.edu |
- 137-16-FB