GlioblastomaNCT03939858
Bioenergetic Profiling and Cognition in GBM Patients
An observational study of Glioblastoma, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma
- What is being tested?
- Cognitive Assessment, Blood Collection and Bioenergetic Profiling
- Type of treatment
- Surgery or procedure
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Oct 2019to 9 Jun 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Glioma patients receiving chemoradiation
Who may be able to join
- Glioma patients greater than 18 years old receiving chemoradiation with a Karnofsky Performance Status greater than or equal to 50.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest Baptist Comprehensive Cancer Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Blood-based Bioenergetic Profiling and Cognition in Glioblastoma Patients
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.
Read the 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.
- Conditions
- Glioblastoma
- Being tested
- Cognitive Assessment, Blood Collection, Bioenergetic Profiling
- Medical subject headings
- Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive AssessmentProcedure or surgery
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.
Blood CollectionDiagnostic test
16 ml of blood will be collected before 10 a.m. and after the participant has fasted for 8 hours. White blood cells and platelets will be used for respirometric analysis. Plasma will be additionally processed and saved in 500uL aliquots(x2) and the remainder in 1mL aliquots at -80°C.
Bioenergetic ProfilingDiagnostic test
Peripheral blood mononuclear cells (PBMCs) and platelets will be separated from the blood. Primary respirometric parameters will be measured with high-throughput respirometry using the Agilent Seahorse 24XFe. Additional parameters will be collected with high-resolution respirometry using the OROBOROS Oxygraph-2k. Both methods will report a variety of mitochondrial parameters resulting in 48 measures per participant, creating robust profiles of bioenergetic health. Additional analysis will include western blots to enumerate protein density for the five major mitochondrial complexes, mtDNA copy number analysis, and citrate synthase activity as these assays provide different but complementary data to respirometry for a more dynamic picture of mitochondrial metabolism.
| Study group | Role | What they receive |
|---|---|---|
| Cognitive Function Analysis | 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. Receives: Procedure: Cognitive Assessment; Diagnostic Test: Blood Collection; Diagnostic Test: Bioenergetic Profiling |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Completing Bioenergetics Profiling
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.
Measured: 3 months
Secondary outcomes (3)
Proportion of Participants with Decline in Cognitive Function
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.
Measured: Three months after completion of radiotherapy
Bioenergetics Profiling Testing - Seahorse XFe24 Analyzer
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.
Measured: Three months after completion of radiotherapy
Bioenergetics Profile Testing - Oroboros O2K
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.
Measured: Three months after completion of radiotherapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2019
- Study start24 Oct 2019
- Primary completion22 Sep 2021
- Study completion9 Jun 2023
Why it stopped: Funding and laboratory access issues, study is closed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe 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
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christina Cramer, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03939858
- Sponsor's protocol ID
- IRB00058347
- Other IDs
- NCI-2019-02984, WFBCCC 01219
- Status last verified
- Nov 2023
- First submitted
- 1 May 2019
- Last updated
- 8 Nov 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Blood-based Bioenergetic Profiling and Cognition in Glioblastoma Patients
- ClinicalTrials.gov ID
- NCT03939858
- Acronym / sponsor ID
- IRB00058347
- Conditions
- Glioblastoma
- Study type
- Observational
- Recruitment status
- TerminatedReason stopped: Funding and laboratory access issues, study is closed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 24 Oct 2019 (actual)
- Primary completion
- 22 Sep 2021 (actual)
- Study completion
- 9 Jun 2023 (actual)
- First posted
- 7 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cognitive Function Analysis | – | Procedure: Cognitive Assessment, Diagnostic Test: Blood Collection, Diagnostic Test: Bioenergetic ProfilingCognitive 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Glioma patients receiving chemoradiation
Key inclusion criteria (1 listed)
- Glioma patients greater than 18 years old receiving chemoradiation with a Karnofsky Performance Status greater than or equal to 50.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive AssessmentTests 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. | Procedure or surgery | Cognitive Function Analysis |
| Blood Collection16 ml of blood will be collected before 10 a.m. and after the participant has fasted for 8 hours. White blood cells and platelets will be used for respirometric analysis. Plasma will be additionally processed and saved in 500uL aliquots(x2) and the remainder in 1mL aliquots at -80°C. | Diagnostic test | Cognitive Function Analysis |
| Bioenergetic ProfilingPeripheral blood mononuclear cells (PBMCs) and platelets will be separated from the blood. Primary respirometric parameters will be measured with high-throughput respirometry using the Agilent Seahorse 24XFe. Additional parameters will be collected with high-resolution respirometry using the OROBOROS Oxygraph-2k. Both methods will report a variety of mitochondrial parameters resulting in 48 measures per participant, creating robust profiles of bioenergetic health. Additional analysis will include western blots to enumerate protein density for the five major mitochondrial complexes, mtDNA copy number analysis, and citrate synthase activity as these assays provide different but complementary data to respirometry for a more dynamic picture of mitochondrial metabolism. | Diagnostic test | Cognitive Function Analysis |
Primary outcome
Number of Patients Completing Bioenergetics Profiling
Time frame: 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.
3 secondary outcomes
Proportion of Participants with Decline in Cognitive Function
Time frame: Three months after completion of radiotherapy
Bioenergetics Profiling Testing - Seahorse XFe24 Analyzer
Time frame: Three months after completion of radiotherapy
Bioenergetics Profile Testing - Oroboros O2K
Time frame: Three months after completion of radiotherapy
Results and safety
The study was stopped early (reason given: Funding and laboratory access issues, study is closed). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Christina Cramer, MD principal investigator
Wake Forest University Health Sciences
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 Glioblastoma, run by Wake Forest University Health Sciences 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 1 inclusion and 8 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: stopped early, as of the sponsor's last update on 8 Nov 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?
The study was stopped early (reason given: Funding and laboratory access issues, study is closed). Results are not available in the source record.
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?
Number of Patients Completing Bioenergetics Profiling (time frame: 3 months). 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 8 Nov 2023.