Bioenergetic Profiling and Cognition in GBM Patients

Terminated

• Conditions: Glioblastoma
• Interventions: Procedure: Cognitive Assessment; Diagnostic Test: Blood Collection; Diagnostic Test: Bioenergetic Profiling

• Registration Number: NCT03939858
• Lead Sponsor: Wake Forest University Health Sciences

Brief Summary

This trial studies the use of blood-based bioenergetic profiling and cognitive testing in assessing patients with glioblastoma undergoing chemoradiation therapy. The purpose of this pilot research study is to find out if it is possible to see changes in participants' mitochondria, parts of a cell that produce energy, that might be associated with changes in participants' brain function after chemoradiation therapy.

Detailed Description

Primary Objective:

• To determine the feasibility of performing bioenergetic profiling in glioblastoma patients receiving chemoradiation by ascertaining the proportion of patients who have enough white blood cells in a 16 mL blood to successfully perform the profiling assays.

Secondary Objectives:

• To determine if either pre-radiotherapy bioenergetic profile or the change in bioenergetic profile from pre-radiotherapy to post-radiotherapy are predictive of subacute cognitive decline after radiation.

OUTLINE: Patients undergo neurocognitive testing over 1 hour using a customized battery of tests designed for brain tumor patients at Wake Forest Baptist Comprehensive Cancer Center. Patients also undergo blood collection at baseline and at 1 and 3 months post radiotherapy.

Study Timeline

• Study First Submitted: 2019-05-01
• Study First Submitted QC: 2019-05-03
• Study First Posted: 2019-05-07
• Study Start: 2019-10-24
• Primary Completion: 2021-09-22
• Study Completion: 2023-06-09
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-06
• Last Update Posted: 2023-11-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 6

Inclusion Criteria

• Glioma patients greater than 18 years old receiving chemoradiation with a Karnofsky Performance Status greater than or equal to 50.

Read More

Exclusion Criteria

• Prior diagnosis (by a physician or neuropsychologist) of any type of dementia (AD, frontotemporal dementia, vascular dementia, Lewy-body dementia, Parkinson's dementia), normal pressure hydrocephalus, Creutzfeldt Jacob disease, posterior cortical atrophy, Huntington's disease, or Korsakoff syndrome will be excluded. Patients who were diagnosed with Mild Cognitive (MCI) Impairment greater than or equal to 1 year prior to diagnosis with their high grade glioma will also be excluded. Patients reported by family members as having memory problems or with subjective memory complaints are still eligible.
• Patients taking medications known to have a mitotoxic effect (see attached appendix). Patients who take any of the as needed medications on the list more than 4 times per week will be excluded. There are medications that are considered mitotoxic that are not included on this list because of the essential nature of the medications to this population (steroids, anti-seizure medications, diabetic medications etc.) or high frequency of use in this population (statins, beta blockers).
• Patients on medications with the potential to enhance cognition including donepezil, memantine, armodafinil or methylphenidate.
• Patients who are not fluent in English will be excluded.
• Patients with aphasia or other neurologic deficit which would prevent participating in cognitive testing will be excluded.
• Patients who are unable to fast for 8 hours will be excluded since enrolled patients will only be able to drink water for the 8 hours before blood draws.
• Patients who drink more than 14 alcoholic drinks per week.
• Patients who are active smokers.

Read More

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Cognitive Function Analysis	Cognitive Assessment	Cognitive function will be evaluated using a customized cognitive battery designed for brain tumor patients. Tests have been selected to represent a range of cognitive functions affected by cancer and radiotherapy including basic attention, recent memory, executive functions (spanning verbal fluency, cognitive set-shifting, and abstract reasoning), and visual perceptual/spatial skills.
Cognitive Function Analysis	Blood Collection	Cognitive function will be evaluated using a customized cognitive battery designed for brain tumor patients. Tests have been selected to represent a range of cognitive functions affected by cancer and radiotherapy including basic attention, recent memory, executive functions (spanning verbal fluency, cognitive set-shifting, and abstract reasoning), and visual perceptual/spatial skills.
Cognitive Function Analysis	Bioenergetic Profiling	Cognitive function will be evaluated using a customized cognitive battery designed for brain tumor patients. Tests have been selected to represent a range of cognitive functions affected by cancer and radiotherapy including basic attention, recent memory, executive functions (spanning verbal fluency, cognitive set-shifting, and abstract reasoning), and visual perceptual/spatial skills.

Primary Outcome Measures

Name	Time	Method
Number of Patients Completing Bioenergetics Profiling	3 months	The primary outcome will be the proportion of patients who are able to have bioenergetic profiling completed at all three time points (baseline, one month after radiotherapy, three months after radiotherapy). The proportion and its 95% confidence interval will be calculated.

Secondary Outcome Measures

Name	Time	Method
Proportion of Participants with Decline in Cognitive Function	Three months after completion of radiotherapy	Cognitive decline as defined as a decline from pre-radiotherapy baseline by one standard deviation on any cognitive test of memory, executive function, or attention at any time point subsequent to baseline. Cognitive function will be evaluated using a customized cognitive battery of tests designed for brain tumor patients at Wake Forest University Comprehensive Cancer Center. Each participant's raw score performance on each assessment measure will be transformed to a z-score, based on available normative data. A composite mean can then be calculated for overall performance to allow for comparison between time points. The proportion of cognitive decline at one-month and 3-month visits will be calculated.
Bioenergetics Profiling Testing - Seahorse XFe24 Analyzer	Three months after completion of radiotherapy	High-throughput respirometry parameters will be collected to compare cognitive decline v. non-decline in participant bioenergetics profile from baseline and at each follow-up visit. The respirometry parameters will be obtained simultaneously (basal respiration, leak respiration, ATP-linked respiration, maximal respiration, spare respiratory capacity and non-mitochondrial respiration). Wilcoxon rank sum test will be used to compare pre-RT bioenergetics profile and the change in bioenergetics profile in the cognitive decline groups (decline vs. non-decline) at each follow-up visit. Simple Spearman's rank correlation coefficients will be used to relate pre-RT bioenergetics profile or change in cognitive testing to change in bioenergetics profile at each follow-up visit.
Bioenergetics Profile Testing - Oroboros O2K	Three months after completion of radiotherapy	High-resolution respirometry parameters will be collected simultaneously to compare cognitive decline v. non-decline in participant bioenergetics profile from baseline and at each follow-up visit - (routine respiration, outer mitochondrial membrane integrity measure, fatty acid β-oxidation mediated respiration, fatty acid β-oxidation and complex I, II and glycerol-3-phosphate dehydrogenase mediated respiration, maximal electron transport chain respiration, spare respiratory capacity, maximal electron transport chain after complex I inhibition, non-mitochondrial respiration, complex IV respiration, leak respiration, complex I and II mediated maximal electron transport chain respiration and cell viability). Wilcoxon rank sum test and Simple Spearman's will be used to compare pre-RT bioenergetics profile and the change in bioenergetics profile in the cognitive decline groups (decline vs. non-decline) at each follow-up visit.

Trial Locations

Locations (1)

Wake Forest Baptist Comprehensive Cancer Center; 🇺🇸 Winston-Salem, North Carolina, United States