The Brain Ketone Body Challenge Imaging Study

NCT03204604 | Withdrawn

• 1 other identifier: IRB00036958
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease

Keywords

Memory; Dietary Treatment

Outcome Measures

Primary Outcomes (1)

• 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.

  2 weeks

Secondary Outcomes (1)

• Secondary Outcome - Memory Composite Score

  2 weeks

Study Arms (2)

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®

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)

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

Interventions

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 A

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 .

Challenge B

PET Scan PROCEDURE

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

Challenge A; Challenge B

Cognitive Testing - FCSRT BEHAVIORAL

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.

Challenge A; Challenge B

Story Recall BEHAVIORAL

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.

Challenge A; Challenge B

BVRT BEHAVIORAL

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.

Challenge A; Challenge B

CogState One Card Learning BEHAVIORAL

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.

Challenge A; Challenge B

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead

Study Sites (1)

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Study Officials

• Timothy R Hughes, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Visits are listed at Challenge A or Challenge B. This serves as a double blind crossover intervention for participants and clinic staff.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Challenge A - low calorie Ensure® shake Challenge B - low calorie Ensure® shake with ketone esters

Study Record Dates

• First Submitted: April 18, 2017
• First Posted: July 2, 2017
• Study Start: August 8, 2016
• Primary Completion: March 1, 2019
• Study Completion: March 1, 2019
• Last Updated: March 19, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)