Alzheimer DiseaseNCT03204604
The Brain Ketone Body Challenge Imaging Study
A study testing Challenge A - low calorie Ensure®, Challenge B - Ensure® plus ketone esters (KE) and PET Scan in people with Alzheimer Disease, run by Wake Forest University Health Sciences at 1 site in United States.
Trial summary
The Brain Ketone Body Challenge Imaging Study will measure how the brain uses different fuels. To do this, radioactive compounds will be used during Positron Emission Tomography (PET) imaging. Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer Disease
- What is being tested?
- Challenge A - low calorie Ensure®, Challenge B - Ensure® plus ketone esters (KE) and PET Scan
- Type of treatment
- Injection or infusion, Surgery or procedure, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Aug 2016to Mar 2019
- Phase
- Interventional
- 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 50 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of Mild Cognitive Impairment (MCI)
- Stable medical condition
- Stable on medications for past 4 weeks
- Women must be post-menopausal
Who cannot join
- Diagnosis of neurodegenerative illness (except for MCI)
- History of a clinically significant stroke
- Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or meeting any Diagnostic and Statistical Manual 4 (DSM-IV) criteria for major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- Diabetes that requires current use of diabetes medications
- Current use of cholesterol/lipid lowering medications
- History of epilepsy or seizure within past year
- Contraindications for imaging (e.g. claustrophobia or high prior radiation exposure)
Trial locations and contacts
1 site in 1 country.
United States1 site
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
The Brain Ketone Body Challenge Imaging Study will measure how the brain uses different fuels. To do this, radioactive compounds will be used during Positron Emission Tomography (PET) imaging.
These compounds, called [11C]Acetoacetate (AcAc) and [18F] Fludeoxyglucose (FDG), are similar to the sugars and fats the brain already uses for fuel. These compounds safely allow researchers to see how the brain uses sugars and fats during PET scans.
Read the detailed description
After consuming a chilled 4 ounce shake which contains various dietary fats, cognitive testing and dual-tracer Positron Emission Tomography scan will be completed. At Visit 1, each participant will be randomized to Challenge A (low calorie Ensure®) or Challenge B (Ensure® plus ketone esters). At Visit 2, each participant will undergo the remaining challenge (A or B) prior to the second imaging session. Each visit is designed to be identical to the other and only vary the dose of ketone esters. Randomization to either Challenge at Visit 1 will ensure that test/re-test learning effects are equally distributed between the challenge groups. This study consists of two visits that will take place over a two week period.
- Conditions
- Alzheimer Disease
- Being tested
- Challenge A - low calorie Ensure®, Challenge B - Ensure® plus ketone esters (KE), PET Scan, Cognitive Testing - FCSRT, Story Recall
- Keywords
- Memory, Dietary Treatment
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Challenge A - low calorie Ensure®Dietary supplement
Challenge A will include a low calorie Ensure shake for the participant to drink with no ketone esters (KE).
Challenge B - Ensure® plus ketone esters (KE)Dietary supplement
Challenge B will include an Ensure shake for the participant to drink with deltaG ketone ester, which has generally recognized as safe (GRAS) supplement status .
PET ScanProcedure or surgery
Subject will drink the shake. Immediate recall memory testing. Subject will be placed in the scanner. Prior to PET acquisition, a low dose CT scan of the head will be obtained for attenuation correction. Patients will be injected with an intravenous bolus of up to 5-10mCi (370 MBq) (+/- 10%) of [11C]AcAc (over 2 minutes). This is the standard dose used in published clinical studies using [11C]AcAc. The PET acquisition will begin immediately after the tracer injection and last for a total of 30 minutes. 2 ml of blood will be sampled from the forearm vein at 3, 6, 8, 12, 20, and 28 minutes post [11C]AcAc tracer injection. This will be used for quantification of radiation estimates throughout the scan-period
Cognitive Testing - FCSRTBehavioural
The Free and Cued Selective Reminding Test (FCSRT) measures verbal memory through multiple trials of a list learning task. A list of 16 items is visually presented to the participants, who then recall as many items as possible. On subsequent trials, participants are told only those items they omitted on the previous trial. The procedure continues until the participant recalls all items on two subsequent trials. After approximately 30-minute delay, participants are asked to recall as many items as possible. The number of items recalled after the delay is then summed.
Story RecallBehavioural
Story Recall: This test is a modification of the episodic memory measure from the Wechsler Memory Scale-Revised (WMS-R). In this modified version, free recall of one short story that consists of 44 bits of information will be elicited immediately after it is read aloud to the participant and again after a thirty-minute delay. The total bits of information from the story that are recalled immediately (maximum score = 44) and after the delay interval (maximum score = 44) are recorded. Six comparable versions of this task have been validated in prior studies with older adults.
BVRTBehavioural
Benton Visual Retention Test (BVRT): The BVRT is a multiple-choice visual recognition task. Participants view a visual pattern and are then asked to select the target from an array of four patterns, three of which are distractors. It assesses visuospatial working memory. This recognition format has the advantage assessing visual memory while eliminating the influence of visuomotor and manual dexterity difficulties.
CogState One Card LearningBehavioural
The One Card Learning Test involves a visual learning task sensitive to early-stage cognitive impairment. It is one of several computerized assessments developed by CogState that assess executive function and working memory.
| Study group | Role | What they receive |
|---|---|---|
| Challenge A | Experimental | Challenge A includes Cognitive testing - (FCSRT, Story Recall, BVRT, CogState One Card Learning), and PET scan with low calorie Ensure® shake containing no ketone esters. Dietary Supplement: Challenge A - low calorie Ensure® Receives: Dietary Supplement: Challenge A - low calorie Ensure®; Procedure: PET Scan; Behavioral: Cognitive Testing - FCSRT; Behavioral: Story Recall; Behavioral: BVRT; Behavioral: CogState One Card Learning |
| Challenge B | Experimental | Challenge B includes Cognitive testing - (FCSRT, Story Recall, BVRT, CogState One Card Learning), and PET scan with an Ensure® shake containing ketone esters. Dietary Supplement: Challenge B - Ensure® plus ketone esters (KE) Receives: Dietary Supplement: Challenge B - Ensure® plus ketone esters (KE); Procedure: PET Scan; Behavioral: Cognitive Testing - FCSRT; Behavioral: Story Recall; Behavioral: BVRT; Behavioral: CogState One Card Learning |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary Outcome - Brain Ketone Utilization
The relative global uptake of [11C]AcAc during Challenge B compared to Challenge A. within each individual. How the brain uses sugars and fats for fuel and who is more likely to respond to dietary treatments.
Measured: 2 weeks
Secondary outcomes (1)
Secondary Outcome - Memory Composite Score
How brain metabolism relates to the developement of memory problems. To look at memory score changes with ketone esters supplementation.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2017
- Study start8 Aug 2016
- Primary completionMar 2019
- Study completionMar 2019
Why it stopped: Unable to obtain intervention materials
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer DiseaseStudies 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Challenge A - low calorie Ensure® shake Challenge B - low calorie Ensure® shake with ketone esters
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Timothy R Hughes, PhD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03204604
- Sponsor's protocol ID
- IRB00036958
- Status last verified
- Mar 2019
- First submitted
- 18 Apr 2017
- Last updated
- 19 Mar 2019
- Results posted
- No
- Data monitoring committee
- 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 19 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Brain Ketone Body Challenge Imaging Study
- ClinicalTrials.gov ID
- NCT03204604
- Acronym / sponsor ID
- IRB00036958
- Conditions
- Alzheimer Disease
- Keywords
- Memory, Dietary Treatment
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Unable to obtain intervention materials
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- 8 Aug 2016 (actual)
- Primary completion
- Mar 2019 (actual)
- Study completion
- Mar 2019 (actual)
- First posted
- 2 Jul 2017 (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.
The Brain Ketone Body Challenge Imaging Study will measure how the brain uses different fuels. To do this, radioactive compounds will be used during Positron Emission Tomography (PET) imaging.
These compounds, called [11C]Acetoacetate (AcAc) and [18F] Fludeoxyglucose (FDG), are similar to the sugars and fats the brain already uses for fuel. These compounds safely allow researchers to see how the brain uses sugars and fats during PET scans.
Detailed description
After consuming a chilled 4 ounce shake which contains various dietary fats, cognitive testing and dual-tracer Positron Emission Tomography scan will be completed. At Visit 1, each participant will be randomized to Challenge A (low calorie Ensure®) or Challenge B (Ensure® plus ketone esters). At Visit 2, each participant will undergo the remaining challenge (A or B) prior to the second imaging session. Each visit is designed to be identical to the other and only vary the dose of ketone esters. Randomization to either Challenge at Visit 1 will ensure that test/re-test learning effects are equally distributed between the challenge groups. This study consists of two visits that will take place over a two week period.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Challenge A - low calorie Ensure® shake Challenge B - low calorie Ensure® shake with ketone esters
| Arm | Type | Receives |
|---|---|---|
| Challenge A | Experimental | Dietary Supplement: Challenge A - low calorie Ensure®, Procedure: PET Scan, Behavioral: Cognitive Testing - FCSRT, Behavioral: Story Recall, Behavioral: BVRT, Behavioral: CogState One Card LearningChallenge A includes Cognitive testing - (FCSRT, Story Recall, BVRT, CogState One Card Learning), and PET scan with low calorie Ensure® shake containing no ketone esters. Dietary Supplement: Challenge A - low calorie Ensure® |
| Challenge B | Experimental | Dietary Supplement: Challenge B - Ensure® plus ketone esters (KE), Procedure: PET Scan, Behavioral: Cognitive Testing - FCSRT, Behavioral: Story Recall, Behavioral: BVRT, Behavioral: CogState One Card LearningChallenge B includes Cognitive testing - (FCSRT, Story Recall, BVRT, CogState One Card Learning), and PET scan with an Ensure® shake containing ketone esters. Dietary Supplement: Challenge B - Ensure® plus ketone esters (KE) |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of Mild Cognitive Impairment (MCI)
- Stable medical condition
- Stable on medications for past 4 weeks
- Women must be post-menopausal
Key exclusion criteria (7 listed)
- Diagnosis of neurodegenerative illness (except for MCI)
- History of a clinically significant stroke
- Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or meeting any Diagnostic and Statistical Manual 4 (DSM-IV) criteria for major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse
- Diabetes that requires current use of diabetes medications
- Current use of cholesterol/lipid lowering medications
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 |
|---|---|---|
| Challenge A - low calorie Ensure®Challenge A will include a low calorie Ensure shake for the participant to drink with no ketone esters (KE). | Dietary supplement | Challenge A |
| Challenge B - Ensure® plus ketone esters (KE)Challenge B will include an Ensure shake for the participant to drink with deltaG ketone ester, which has generally recognized as safe (GRAS) supplement status . | Dietary supplement | Challenge B |
| PET ScanSubject will drink the shake. Immediate recall memory testing. Subject will be placed in the scanner. Prior to PET acquisition, a low dose CT scan of the head will be obtained for attenuation correction. Patients will be injected with an intravenous bolus of up to 5-10mCi (370 MBq) (+/- 10%) of [11C]AcAc (over 2 minutes). This is the standard dose used in published clinical studies using [11C]AcAc. The PET acquisition will begin immediately after the tracer injection and last for a total of 30 minutes. 2 ml of blood will be sampled from the forearm vein at 3, 6, 8, 12, 20, and 28 minutes post [11C]AcAc tracer injection. This will be used for quantification of radiation estimates throughout the scan-period | Procedure or surgery | Challenge A, Challenge B |
| Cognitive Testing - FCSRTThe Free and Cued Selective Reminding Test (FCSRT) measures verbal memory through multiple trials of a list learning task. A list of 16 items is visually presented to the participants, who then recall as many items as possible. On subsequent trials, participants are told only those items they omitted on the previous trial. The procedure continues until the participant recalls all items on two subsequent trials. After approximately 30-minute delay, participants are asked to recall as many items as possible. The number of items recalled after the delay is then summed. | Behavioural | Challenge A, Challenge B |
| Story RecallStory Recall: This test is a modification of the episodic memory measure from the Wechsler Memory Scale-Revised (WMS-R). In this modified version, free recall of one short story that consists of 44 bits of information will be elicited immediately after it is read aloud to the participant and again after a thirty-minute delay. The total bits of information from the story that are recalled immediately (maximum score = 44) and after the delay interval (maximum score = 44) are recorded. Six comparable versions of this task have been validated in prior studies with older adults. | Behavioural | Challenge A, Challenge B |
| BVRTBenton Visual Retention Test (BVRT): The BVRT is a multiple-choice visual recognition task. Participants view a visual pattern and are then asked to select the target from an array of four patterns, three of which are distractors. It assesses visuospatial working memory. This recognition format has the advantage assessing visual memory while eliminating the influence of visuomotor and manual dexterity difficulties. | Behavioural | Challenge A, Challenge B |
| CogState One Card LearningThe One Card Learning Test involves a visual learning task sensitive to early-stage cognitive impairment. It is one of several computerized assessments developed by CogState that assess executive function and working memory. | Behavioural | Challenge A, Challenge B |
Primary outcome
Primary Outcome - Brain Ketone Utilization
Time frame: 2 weeks
The relative global uptake of [11C]AcAc during Challenge B compared to Challenge A. within each individual. How the brain uses sugars and fats for fuel and who is more likely to respond to dietary treatments.
1 secondary outcome
Secondary Outcome - Memory Composite Score
Time frame: 2 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2019.
- 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.
Timothy R Hughes, PhD 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?
A study testing Challenge A - low calorie Ensure®, Challenge B - Ensure® plus ketone esters (KE) and PET Scan in people with Alzheimer Disease, 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 4 inclusion and 7 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: withdrawn, as of the sponsor's last update on 19 Mar 2019. 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 withdrawn before enrolling participants, so there are no results.
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?
Primary Outcome - Brain Ketone Utilization (time frame: 2 weeks). 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 19 Mar 2019.