cognitive alterations, tau-protein expression, glutamate expression, LGG
Conditions
Interventions
Prior to inclusion in the T-Pacing study, patients will have undergone routine diagnostic screening procedures, consisting of at least a pre-operative neurocognitive assessment. After consent for the
a [18F]flortaucipir tau PET/CT scan before and two years after the surgery. During the two-year follow-up, patients will perform neurocognitive assessment 6-weeks post-surgery, 4 months (clinical care
Sponsors
Universitair Medisch Centrum Utrecht
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: Age =18 year and =50 year at the time of consent, given the increase in significant Tau protein deposits from the age of 50;Suspected de novo IDH-mt LGG or untreated (biopsied) IDH-mt LGG without signs of dedifferentiation;Karnofsky Performance Score = 70
Exclusion criteria
Exclusion criteria: Unwilling or unable to undergo 7T MRI based on the 7T MRI screening checklist;History of any clinically significant cardiovascular, endocrinology, hematologic, hepatobiliary, immunologic, metabolic, urologic, pulmonary, neurologic, psychiatric, renal or other major disease, as determined by the principal investigator;Previous oncogenic glioma treatment (i.e. debulking surgery, radiation therapy, chemotherapy, immunotherapy);Female patients who are pregnant at the time screening cannot participate in the study. Breastfeeding women are advised to avoid breastfeeding for 4 hours after [18F]flortaucipir administration;Has a relevant history of severe drug allergy or hypersensitivity. Relevant severe drug allergies should be determined by the investigator;Has been injected with a previously administered radiopharmaceutical within 6 terminal half-lives or when total yearly radiation exposure for research exceeds 11.3 mSv for females and 15.3 mSv for males;Meets clinical diagnostic criteria for either Alzheimer dementia of frontotemporal dementia.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The main parameters of this study are pre-surgery prevalence and distribution of Tau protein deposits and Glutamate and change in NCA test scores from pre-surgery to two-years post-surgery. Segmentations of these expression will be constructed and compared to the segmented tumor lesion in order to assess the pattern throughout the brain (in- or outside of the tumors). The cognitive change will be assessed using an reliable change index (RCI) to reflect reliable and meaningful cognitive changes.36–38 To assess both the magnitude of the cognitive change as well as the possible clinical impact of this change, change in NCA scores will be formalized both as a continuous measure of change (RCI) as well as the number of patients that show a significant decline based on the RCI (i.e. ‘events’). The primary objectives of this study are to evaluate the prevalence and distribution of Tau protein (determined with [18F]flortaucipir PET/CT) and Glutamate (as determined with 2HG MRS) deposits in both brain and glioma tissues. Understanding these patterns will provide insight into whether the presence of glioma is associated with increased levels of Tau protein and/or Glutamate, and if these deposits are localized to the tumor vicinity or dispersed throughout the brain. The second through fourth main objectives are to assess the relationship between the prevalence and distribution of Tau protein deposits and cognitive deficits pre-surgery and cognitive changes over time in patients. This will help to determine if cognitive decline can be attributed to the presence of Tau protein deposits, and whether specific brain regions with these deposits are particularly associated with cognitive decline. This investigation will enhance our understanding of the mechanisms underlying cognitive decline in patients with LGG. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary analyses will focus on improving the understanding of the mechanisms underlying the relationship between Tau deposits, Glutamate and cognitive change over time in patients with LGG through the below mentioned analyses:Assessment of the changes in cognitive performance during the two-year follow-up and its relation to histological markers previously associated with cognitive performance, clinical/treatment variables (e.g. extent of resection, additional anti-tumor treatments, etc.)Assessment of the changes in the prevalence and distribution of Tau-protein deposits two years following initial treatment. Assess the relationship between histological markers previously associated with cognitive performance and pre-surgery, two-year post-surgery, and two-year change in Tau protein deposits. Assess the relationship between histological markers previously associated with cognitive performance and pre-surgery Glutamate. Assess the relationship between Glutamate, Glutamine and 2HG levels derived from 7T MRS and cognitive change during the two-year follow-up. Determine whether distribution patterns of Glutamate and Tau-protein are analogous to those reported in the literature for other conditions, such as AD. | — |
Countries
Netherlands
Contacts
Public ContactP. A. J. T. Robe
Universitair Medisch Centrum Utrecht
Outcome results
None listed