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The Brain Ketone Body Challenge Imaging Study

Primary Purpose

Alzheimer Disease

Status

Withdrawn

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Challenge A - low calorie Ensure®

Challenge B - Ensure® plus ketone esters (KE)

PET Scan

Cognitive Testing - FCSRT

Story Recall

BVRT

CogState One Card Learning

About this trial

This is an interventional basic science trial for Alzheimer Disease focused on measuring Memory, Dietary Treatment

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Wake Forest School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Challenge A

Challenge B

Arm Description

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®

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT03204604

First Posted

April 18, 2017

Last Updated

March 15, 2019

Sponsor

Wake Forest University Health Sciences

1. Study Identification

Unique Protocol Identification Number

NCT03204604

Brief Title

The Brain Ketone Body Challenge Imaging Study

Official Title

The Brain Ketone Body Challenge Imaging Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2019

Overall Recruitment Status

Withdrawn

Why Stopped

Unable to obtain intervention materials

Study Start Date

August 8, 2016 (Actual)

Primary Completion Date

March 2019 (Actual)

Study Completion Date

March 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Wake Forest University Health Sciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Alzheimer Disease

Keywords

Memory, Dietary Treatment

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

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

Masking

ParticipantCare ProviderInvestigator

Masking Description

Visits are listed at Challenge A or Challenge B. This serves as a double blind crossover intervention for participants and clinic staff.

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Challenge A

Arm Type

Experimental

Arm Description

Arm Title

Challenge B

Arm Type

Experimental

Arm Description

Intervention Type

Dietary Supplement

Intervention Name(s)

Challenge A - low calorie Ensure®

Intervention Description

Challenge A will include a low calorie Ensure shake for the participant to drink with no ketone esters (KE).

Intervention Type

Dietary Supplement

Intervention Name(s)

Challenge B - Ensure® plus ketone esters (KE)

Intervention Description

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 .

Intervention Type

Procedure

Intervention Name(s)

PET Scan

Intervention Description

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

Intervention Type

Behavioral

Intervention Name(s)

Cognitive Testing - FCSRT

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

Story Recall

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

BVRT

Intervention Description

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.

Intervention Type

Behavioral

Intervention Name(s)

CogState One Card Learning

Intervention Description

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 Measure Information:

Title

Primary Outcome - Brain Ketone Utilization

Description

Time Frame

2 weeks

Secondary Outcome Measure Information:

Title

Secondary Outcome - Memory Composite Score

Description

How brain metabolism relates to the developement of memory problems. To look at memory score changes with ketone esters supplementation.

Time Frame

2 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

50 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy R Hughes, PhD

Organizational Affiliation

Wake Forest University Health Sciences

Official's Role

Principal Investigator

Facility Information:

Facility Name

Wake Forest School of Medicine

City

Winston-Salem

State/Province

North Carolina

ZIP/Postal Code

27157

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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