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Apolipoprotein E (APOE) Genotype Effects on Triglycerides and Blood Flow in the Human Brain

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ClinicalTrials.gov Identifier: NCT04692441
Recruitment Status : Recruiting
First Posted : December 31, 2020
Last Update Posted : June 11, 2021
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Angela Hanson, University of Washington

Brief Summary:
High fat feeding (HFF) increases the risk of Alzheimer's disease (AD) but individuals who carry the AD risk gene E4 paradoxically improve after acute HFF. The investigators propose to further study this phenomenon with a clinical study to assess cerebral blood flow which can be measured by a technique called arterial spin labeling (ASL) on an MRI and is tightly related to brain metabolism.

Condition or disease Intervention/treatment Phase
Alzheimer Disease Dementia Dietary Supplement: Heavy Cream Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Each participant undergoes the same intervention
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: APOE Genotype Effects on Triglycerides and Blood Flow in the Human Brain
Actual Study Start Date : May 1, 2021
Estimated Primary Completion Date : June 30, 2025
Estimated Study Completion Date : December 31, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Intervention
All participants undergo the same intervention: Drinking heavy cream and undergoing MRI.
Dietary Supplement: Heavy Cream
100 ml of dairy cream with 40.4g of total fat, to ingest orally




Primary Outcome Measures :
  1. Difference in global cerebral blood flow between baseline and 2 hours post lipid ingestion (Change CBF) [ Time Frame: 2 Hour Change ]
    Change in global cerebral blood flow (CBF) in ml/100g/min, calculated as the subtracted difference between the pre- and the post-ASL flow in response to the intervention.


Secondary Outcome Measures :
  1. Change in regional CBF [ Time Frame: 2 Hour Change ]
    Change in regional cerebral blood flow (standard brain regions identified using standard Harvard-Oxford Cortical and Subcortical atlas) in ml/100g/ min, calculated as the difference between the pre- and the post-ASL flow in response to the intervention.

  2. Fluid Cognitive Composite Standard Score [ Time Frame: 3 hours post-drink ingestion ]
    The fluid cognitive composite standard score, from the National Institute of Health Toolbox cognitive assessment. Scores are expressed as normalized averages. Scores range from 0 to 140; a score of 100 represents an average ability, and higher scores indicate an above-average ability.


Other Outcome Measures:
  1. Change in global cerebral blood flow as correlated with exploratory factors [ Time Frame: 2 Hour Change ]
    Exploratory factors include fasting lipid levels, fasting and 2 hour OGTT glucose levels, hemoglobin A1C, and fat mass as assessed by DEXA.

  2. Change in regional cerebral blood flow as correlated with exploratory factors [ Time Frame: 2 Hour Change ]
    Exploratory factors include fasting lipid levels, fasting and 2 hour OGTT glucose levels, hemoglobin A1C, and fat mass as assessed by DEXA.



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Ages Eligible for Study:   55 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Aged 55 or older at the date of the screening visit
  2. Equal representation of APOE E4 carriers and non-carriers
  3. Strive for equal numbers of men and women; women need to be post-menopausal for at least 1 year or medical equivalent (hysterectomy)
  4. Able to read and understand English
  5. Able to cognitively and physically give informed consent 6.Able to undergo an MRI and ingest dairy products

Exclusion Criteria:

  1. Diabetes requiring medication: Known type 1 or type 2 diabetes requiring oral diabetic medications or insulin. Diet-controlled diabetes, 'pre-diabetes,' remote use of diabetic agents, or a history of gestational diabetes is ok to enroll.
  2. Hypertension requiring medication: Participants taking medication for hypertension will be excluded, unless they can safely stop the medication for 2 weeks, per their primary care provider, before the study visit (The MRI visit).
  3. Significant lipid abnormalities: Diagnosis of hyperlipidemia requiring statin, bile acid resins, fibrate medications, and/or high dose niacin will be excluded. If participants are willing to stop their medications 4 weeks before the screening visit (as long as they are not on medication for secondary prevention of heart attack or stroke), this is ok. If participants are taking over-the-counter medications known to affect lipid metabolism including omega-3 fatty acids, niacin, or red yeast rice, they can enroll if they agree to stop the medication 4 weeks before the screening visit. Also excluded are significant cholesterol abnormalities as defined by the 2018 American College of Cardiology/American Heart Association (ACC/AHA) lipid guidelines including a fasting LDL cholesterol ≥190 mg/dL or fasting triglycerides > 500 mg/dL. Total cholesterol levels and HDL levels outside of the typical range are ok.
  4. Dementia and cognitive impairment: Known diagnosis of dementia, use of dementia medications, or identification of dementia during the baseline visit, will be excluded. Also excluded are other significant neurologic diseases which affect cognition, such as recent stroke, recent severe head injury, or advanced Parkinson's disease. Mild cognitive impairment with no functional deficits is ok.
  5. Psychiatric disorders: Participants who report active untreated major depression, psychosis, or mania, or who present with those symptoms at the baseline visit, or who act belligerent or unprofessional toward the clinical staff, will be excluded. Psychiatric conditions which are stable and treated with medication or therapy are ok. Similarly, individuals who meet criteria for active alcohol or drug abuse disorder will also be excluded as many of these substances could affect the study outcome.
  6. Other significant medical illnesses: Illnesses which would cause a hardship on the participant to attend study visits and undergo a glucose tolerance test and an MRI. This includes unstable angina, moderate or severe chronic obstructive pulmonary disease (COPD), class III-IV Congestive heart failure (CHF), active liver or kidney disease causing cognitive symptoms, active cancer undergoing systemic chemotherapy or radiation, as well as other illnesses which in the study physician's view would put the participant at risk and also may place an undue burden on the participant.
  7. Major digestive disorders: Disorders which would affect fat tolerance and absorption will be excluded including inflammatory bowel disease, gastric bypass or banding, or small intestine resection. Also excluded are allergies or major intolerance to milk or dairy products.
  8. Contraindications to MRI: Metal in body that is not compatible with an MRI, other conditions that preclude an MRI (such as not being able to lie still or lie flat for an extended time) are excluded.

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): NCT04692441


Contacts
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Contact: Angela J Hanson, MD 206-897-5393 hansonlab@uw.edu

Locations
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United States, Washington
University of Washington Medical Center Recruiting
Seattle, Washington, United States, 98195
Principal Investigator: Angela Hanson, MD         
Sponsors and Collaborators
University of Washington
National Institute on Aging (NIA)
Investigators
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Principal Investigator: Angela J Hanson, MD University of Washington
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Responsible Party: Angela Hanson, Assistant Professor, School of Medicine, University of Washington
ClinicalTrials.gov Identifier: NCT04692441    
Other Study ID Numbers: STUDY00009772
1R01AG067563-01 ( U.S. NIH Grant/Contract )
First Posted: December 31, 2020    Key Record Dates
Last Update Posted: June 11, 2021
Last Verified: June 2021
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 Angela Hanson, University of Washington:
APOE genotype
lipid metabolism
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