Ignite Creation Date:
2024-05-06 @ 6:56 PM
Last Modification Date:
2024-10-26 @ 2:57 PM
Study NCT ID:
NCT05840575
Status:
RECRUITING
Last Update Posted:
2023-05-03
First Post:
2023-01-25
Brief Title:
Investigating Cognitive Impairment in Young Patients With Cancer Prospectively
Sponsor:
Rigshospitalet Denmark
Organization:
Rigshospitalet Denmark
Study Overview
Official Title:
A Multidisciplinary Neuroscience Approach to Investigate Cognitive Impairment in Young Patients With Cancer Prospectively
Status:
RECRUITING
Status Verified Date:
2023-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MyBrain
Brief Summary:
The MyBrain study investigates the brain function of children adolescents and young adults during and after chemo treatment for cancer The tests include 1 cognitive skills such as memory and attention 2 the brains electrical activity 3 and biological markers related to brain function
The aim of the study is to better understand the trajectories of cognitive functioning and measures that have been associated with cognitive impairment in patients treated with chemotherapy
The aim of the study is to better understand the trajectories of cognitive functioning and measures that have been associated with cognitive impairment in patients treated with chemotherapy
Detailed Description:
Background
Numerous studies indicate that many patients with cancer regardless of cancer type develop cancer-related cognitive impairment CRCI which may persist for many years after ended treatment CRCI can occur regardless of cancer type and most often affects cognitive domains such as memory attention processing speed and executive functions In daily life this may manifest as difficulties in attention and concentration learning multitasking mentally organize tasks and cognitive fatigue The cognitive impact of cancer and cancer treatments for non-CNS patients has been shown with several research disciplines such as neuropsychological tests neuroimaging biomarkers and animal studies
Cognitive impairment affects children adolescents and young adults with cancer and their families Young cancer patients may be particularly vulnerable to cognitive impairment as the brain undergoes development in childhood and continues into the twenties However there is a lack of knowledge about when a decrease in cognitive capacity may occur how long it will persist and which cognitive domains are affected for children adolescents and young adults with cancer
Aim
MyBrain is an explorative study which will explore and describe trajectories of CRCI as measured by neuropsychological assessment self-reported quality of life and fatigue brain functioning measured with electroencephalogram EEG and biomarkers of neural impairment and inflammation
Design
Single-centre prospective longitudinal study including patients diagnosed with cancers outside the brain at age 7-29 years Each patient is paired with a healthy control matched on age and social circle
Time points
The MyBrain study includes patients with different cancer types and assigned to different treatment protocols Therefore some patients will undergo treatment for several months for instance testicular cancer lymphomas while others will be treated over several years acute lymphoblastic leukaemia The measurement time points will vary between different protocols
T0 Patients are assessed as close to the day of diagnosis as possible within 30 days from the day they receive their diagnosis
T1abc Up to three time points 2-3 during chemo treatment Blood samples will be taken immediately before and 10-14 days after the chemo dosing for the specific chemo cycles For patients who receive more than three cycles of chemotherapy the timepoints T1abc will be placed at the chemo treatments with the highest doses denoted the major chemo treatments according to the treatment protocol the patient follows If the treatment protocol allocates the same dose to all chemo treatments the T1abc will be placed with the aim to obtain approximate equidistance between T0 T1abc and T2
HDM1-3 Three additional time points during treatment for the patients who are treated with high dose methotrexate HDM Blood samples will be taken immediately before and 10-14 days after HDM treatment
T2 End of treatment End of treatment is defined as two weeks after the final antineoplastic treatment For ALL patients end of treatment is defined as the end of consolidation treatment
T3 Follow-up 6 months after T2
All outcome measures are collected at the time points T0 T2 and T3 for patients and at similar time intervals for controls T1abc and HDM1-3 only includes biological samples from the patients
Data includes
Clinical information obtained from medical charts including cancer diagnosis treatment protocol duration of treatment and adverse events
Sociodemographic information collected with a brief questionnaire which includes level of education occupation economic status and the parents level of education and occupation
Cognitive functioning assessed with a clinical battery The battery includes Nepsy-II Verbal Fluency Wechsler Coding WISC-V or WAIS-IV Wechsler Symbol Search WISC-V or WAIS-IV RBANS Word List Memory RBANS Word List memory recall RBANS Word List memory recognition Wechsler Vocabulary WISC-V or WAIS-IV Wechsler Matrix WISC-V or WAIS-IV Digit Span WISC-V or WAIS-IV Conners CPT-III Grooved Pegboard For the Wechler tests participants 16 years of age are tested with WISC-V and participants 16 or older are tested with WAIS-IV
Cognitive functioning assessed with the Cambridge Neuropsychological Test Automated Battery CANTAB The following tests are included Spatial Working Memory Pattern Recognition Memory Spatial Span Paired Associates Learning Pattern Recognition Memory delayed Delayed Matching to Sample
Qualitive of life measured with the Pediatric Quality of Life Inventory PedsQL Generic Core Scales 40
Fatigue measured with the PedsQL Multidimensional Fatigue Scales 30
Resting state EEG is recorded with eyes-open EO and eyes-closed EC in four blocks of three minutes each EO-EC-EO-EC
Event-related potentials ERP during a two-tone auditory oddball task The participants are instructed to mentally count the rare stimulus
Biomarkers of associated with cognitive functioning measured in serum neurofilament light chain glial fibrillary acidic protein brain derived neurotrophic factor and pro- and anti-inflammatory markers IFNy IL10 IL12p70 IL17A IL6 TNFa and IL1β
Biomarkers of associated with cognitive functioning measured in cerebrospinal fluid CSF for the haematological patients if CSF is drawn as part of their treatment neurofilament light chain glial fibrillary acidic protein brain derived neurotrophic factor pro- and anti-inflammatory markers
Data analyses Large inhomogeneity in the data is expected due to the inclusion of patients over a wide age-span with different cancer types varying treatment protocols and varying timelines from diagnosis to end of treatment and there are no predefined specific hypotheses due to the many sources of inhomogeneity All analyses are exploratory and confidence limits rather than nominal p-values will be used as the indication of the strength of an association when quantified in statistical analyses
The initial analyses will be data visualizations of quantitative variables will include trajectories for single variables bivariate plots with smoothed mean curves added and plots of patient observations against the corresponding observations for the matched control connecting the points in temporal order for each matched pair The trajectories will be presented for different timescales eg time since diagnosis or time from T2 Potential risk factors like cancer type sex or age will be indicated in the data visualizations by using different colours and symbols
Neurocognitive test scores will be investigated at each time point T0 T2 and T3 for each subtest Raw as well as scaled scores age-adjusted from Danish population norms will be used in the analysis For the visualizations of the raw test scores the scores will be plotted as a function of age including reference curves based on back-converted means SD and -2 SD
Numerous studies indicate that many patients with cancer regardless of cancer type develop cancer-related cognitive impairment CRCI which may persist for many years after ended treatment CRCI can occur regardless of cancer type and most often affects cognitive domains such as memory attention processing speed and executive functions In daily life this may manifest as difficulties in attention and concentration learning multitasking mentally organize tasks and cognitive fatigue The cognitive impact of cancer and cancer treatments for non-CNS patients has been shown with several research disciplines such as neuropsychological tests neuroimaging biomarkers and animal studies
Cognitive impairment affects children adolescents and young adults with cancer and their families Young cancer patients may be particularly vulnerable to cognitive impairment as the brain undergoes development in childhood and continues into the twenties However there is a lack of knowledge about when a decrease in cognitive capacity may occur how long it will persist and which cognitive domains are affected for children adolescents and young adults with cancer
Aim
MyBrain is an explorative study which will explore and describe trajectories of CRCI as measured by neuropsychological assessment self-reported quality of life and fatigue brain functioning measured with electroencephalogram EEG and biomarkers of neural impairment and inflammation
Design
Single-centre prospective longitudinal study including patients diagnosed with cancers outside the brain at age 7-29 years Each patient is paired with a healthy control matched on age and social circle
Time points
The MyBrain study includes patients with different cancer types and assigned to different treatment protocols Therefore some patients will undergo treatment for several months for instance testicular cancer lymphomas while others will be treated over several years acute lymphoblastic leukaemia The measurement time points will vary between different protocols
T0 Patients are assessed as close to the day of diagnosis as possible within 30 days from the day they receive their diagnosis
T1abc Up to three time points 2-3 during chemo treatment Blood samples will be taken immediately before and 10-14 days after the chemo dosing for the specific chemo cycles For patients who receive more than three cycles of chemotherapy the timepoints T1abc will be placed at the chemo treatments with the highest doses denoted the major chemo treatments according to the treatment protocol the patient follows If the treatment protocol allocates the same dose to all chemo treatments the T1abc will be placed with the aim to obtain approximate equidistance between T0 T1abc and T2
HDM1-3 Three additional time points during treatment for the patients who are treated with high dose methotrexate HDM Blood samples will be taken immediately before and 10-14 days after HDM treatment
T2 End of treatment End of treatment is defined as two weeks after the final antineoplastic treatment For ALL patients end of treatment is defined as the end of consolidation treatment
T3 Follow-up 6 months after T2
All outcome measures are collected at the time points T0 T2 and T3 for patients and at similar time intervals for controls T1abc and HDM1-3 only includes biological samples from the patients
Data includes
Clinical information obtained from medical charts including cancer diagnosis treatment protocol duration of treatment and adverse events
Sociodemographic information collected with a brief questionnaire which includes level of education occupation economic status and the parents level of education and occupation
Cognitive functioning assessed with a clinical battery The battery includes Nepsy-II Verbal Fluency Wechsler Coding WISC-V or WAIS-IV Wechsler Symbol Search WISC-V or WAIS-IV RBANS Word List Memory RBANS Word List memory recall RBANS Word List memory recognition Wechsler Vocabulary WISC-V or WAIS-IV Wechsler Matrix WISC-V or WAIS-IV Digit Span WISC-V or WAIS-IV Conners CPT-III Grooved Pegboard For the Wechler tests participants 16 years of age are tested with WISC-V and participants 16 or older are tested with WAIS-IV
Cognitive functioning assessed with the Cambridge Neuropsychological Test Automated Battery CANTAB The following tests are included Spatial Working Memory Pattern Recognition Memory Spatial Span Paired Associates Learning Pattern Recognition Memory delayed Delayed Matching to Sample
Qualitive of life measured with the Pediatric Quality of Life Inventory PedsQL Generic Core Scales 40
Fatigue measured with the PedsQL Multidimensional Fatigue Scales 30
Resting state EEG is recorded with eyes-open EO and eyes-closed EC in four blocks of three minutes each EO-EC-EO-EC
Event-related potentials ERP during a two-tone auditory oddball task The participants are instructed to mentally count the rare stimulus
Biomarkers of associated with cognitive functioning measured in serum neurofilament light chain glial fibrillary acidic protein brain derived neurotrophic factor and pro- and anti-inflammatory markers IFNy IL10 IL12p70 IL17A IL6 TNFa and IL1β
Biomarkers of associated with cognitive functioning measured in cerebrospinal fluid CSF for the haematological patients if CSF is drawn as part of their treatment neurofilament light chain glial fibrillary acidic protein brain derived neurotrophic factor pro- and anti-inflammatory markers
Data analyses Large inhomogeneity in the data is expected due to the inclusion of patients over a wide age-span with different cancer types varying treatment protocols and varying timelines from diagnosis to end of treatment and there are no predefined specific hypotheses due to the many sources of inhomogeneity All analyses are exploratory and confidence limits rather than nominal p-values will be used as the indication of the strength of an association when quantified in statistical analyses
The initial analyses will be data visualizations of quantitative variables will include trajectories for single variables bivariate plots with smoothed mean curves added and plots of patient observations against the corresponding observations for the matched control connecting the points in temporal order for each matched pair The trajectories will be presented for different timescales eg time since diagnosis or time from T2 Potential risk factors like cancer type sex or age will be indicated in the data visualizations by using different colours and symbols
Neurocognitive test scores will be investigated at each time point T0 T2 and T3 for each subtest Raw as well as scaled scores age-adjusted from Danish population norms will be used in the analysis For the visualizations of the raw test scores the scores will be plotted as a function of age including reference curves based on back-converted means SD and -2 SD
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None