Myelodysplastic SyndromeChemobrainNCT02767388
Electrophysiological Biomarkers of Chemotherapy-related Cognitive Impairment and Recovery
An observational study of Myelodysplastic Syndrome and Effects of Chemotherapy, run by University of Nebraska at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 19 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Myelodysplastic Syndrome, Effects of Chemotherapy, Mild Cognitive Impairment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2016to 15 Mar 2018
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: The 2008 World Health Organization (WHO) classification is used to diagnose MDS. Patients diagnosed with MDS are stratified into one of five risk categories, based on a prognostic score calculated according to the revised International Prognostics Scoring System (IPSS-R): very-low risk, low risk, intermediate risk, high risk, and very-high risk. IPSS-R scores are estimated from percent of bone marrow blasts, number and depth of cytopenias, and presence of specific cytogenetic abnormalities, collectively reflecting the total number of risk factors.
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center
Omaha, Nebraska, 68132
About this study
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.
Read the 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.
- Conditions
- Myelodysplastic Syndrome, Effects of Chemotherapy, Mild Cognitive Impairment, Multiple Myeloma, Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Medical subject headings
- Myelodysplastic Syndromes, Cognitive Dysfunction, Multiple Myeloma, Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline Capture Task Performance at 1- and 3- Months
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.
Measured: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction
Change From Baseline N2pc Amplitude at 1- and 3- Months
Electrophysiological component that measures allocation of attentional resources
Measured: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction
Change From Baseline Filter Task Performance at 1- and 3- Months
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.
Measured: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction
Change From Baseline CDA Amplitude at 1- and 3- Months
Electrophysiological component that measures online storage load
Measured: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2016 (estimated)
- Study start1 Sep 2016
- Primary completion11 Dec 2017
- Study completion15 Mar 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromeStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Vijaya Bhatt, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02767388
- Sponsor's protocol ID
- 0137-16-EP
- Acronym
- Chemobrain
- Status last verified
- Sep 2023
- First submitted
- 22 Apr 2016
- Last updated
- 29 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Electrophysiological Biomarkers of Chemotherapy-related Cognitive Impairment and Recovery
- ClinicalTrials.gov ID
- NCT02767388
- Acronym / sponsor ID
- Chemobrain / 0137-16-EP
- Conditions
- Myelodysplastic Syndrome, Effects of Chemotherapy, Mild Cognitive Impairment, Multiple Myeloma, Non-hodgkin Lymphoma, Chronic Lymphocytic Leukemia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Study start
- 1 Sep 2016 (actual)
- Primary completion
- 11 Dec 2017 (actual)
- Study completion
- 15 Mar 2018 (actual)
- First posted
- 10 May 2016 (estimated)
- Results
- Posted 6 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 19 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- The 2008 World Health Organization (WHO) classification is used to diagnose MDS. Patients diagnosed with MDS are stratified into one of five risk categories, based on a prognostic score calculated according to the revised International Prognostics Scoring System (IPSS-R): very-low risk, low risk, intermediate risk, high risk, and very-high risk. IPSS-R scores are estimated from percent of bone marrow blasts, number and depth of cytopenias, and presence of specific cytogenetic abnormalities, collectively reflecting the total number of risk factors.
Key inclusion criteria (5 listed)
- 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)
Key exclusion criteria (3 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Change From Baseline Capture Task Performance at 1- and 3- Months
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction
Electrophysiological component that measures online storage load
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Myelodysplastic Syndromes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vijaya Bhatt, MD principal investigator
University of Nebraska
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Myelodysplastic Syndrome and Effects of Chemotherapy, run by University of Nebraska at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline Capture Task Performance at 1- and 3- Months (time frame: Collected at Study Induction, 1 month after Study Induction, 3 months after Study Induction). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2023; AzTrials last refreshed its copy on 8 Nov 2026.