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The Brain Ketone Body Challenge Imaging Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03204604
Recruitment Status : Withdrawn (Unable to obtain intervention materials)
First Posted : July 2, 2017
Last Update Posted : March 19, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief 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.

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.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Dietary Supplement: Challenge A - low calorie Ensure® 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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Challenge A - low calorie Ensure® shake Challenge B - low calorie Ensure® shake with ketone esters
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Visits are listed at Challenge A or Challenge B. This serves as a double blind crossover intervention for participants and clinic staff.
Primary Purpose: Basic Science
Official Title: The Brain Ketone Body Challenge Imaging Study
Actual Study Start Date : August 8, 2016
Actual Primary Completion Date : March 2019
Actual Study Completion Date : March 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Challenge A
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®
Dietary Supplement: Challenge A - low calorie Ensure®
Challenge A will include a low calorie Ensure shake for the participant to drink with no ketone esters (KE).

Procedure: PET Scan
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

Behavioral: Cognitive Testing - FCSRT
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.

Behavioral: Story Recall
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.

Behavioral: BVRT
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.

Behavioral: CogState One Card Learning
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.

Experimental: Challenge B
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)
Dietary Supplement: 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 .

Procedure: PET Scan
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

Behavioral: Cognitive Testing - FCSRT
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.

Behavioral: Story Recall
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.

Behavioral: BVRT
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.

Behavioral: CogState One Card Learning
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.




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Secondary Outcome - Memory Composite Score [ Time Frame: 2 weeks ]
    How brain metabolism relates to the developement of memory problems. To look at memory score changes with ketone esters supplementation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of Mild Cognitive Impairment (MCI)
  • Stable medical condition
  • Stable on medications for past 4 weeks
  • Women must be post-menopausal

Exclusion Criteria:

  • 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03204604


Locations
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United States, North Carolina
Wake Forest School of Medicine
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Timothy R Hughes, PhD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03204604    
Other Study ID Numbers: IRB00036958
First Posted: July 2, 2017    Key Record Dates
Last Update Posted: March 19, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Wake Forest University Health Sciences:
Memory
Dietary Treatment
Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders