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

NCT04692441 | Recruiting

• 2 other identifiers: STUDY000097721R01AG067563-01
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Alzheimer Disease; Dementia

Keywords

APOE genotype; lipid metabolism

Outcome Measures

Primary Outcomes (1)

• Difference in global cerebral blood flow between baseline and 2 hours post lipid ingestion (Change CBF)

  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.

  2 Hour Change

Secondary Outcomes (2)

• Change in regional CBF

  2 Hour Change

• Fluid Cognitive Composite Standard Score

  3 hours post-drink ingestion

Other Outcomes (2)

• Change in global cerebral blood flow as correlated with exploratory factors

  2 Hour Change

• Change in regional cerebral blood flow as correlated with exploratory factors

  2 Hour Change

Study Arms (1)

Intervention

OTHER

All participants undergo the same intervention: Drinking heavy cream and undergoing MRI.

Dietary Supplement: Heavy Cream

Interventions

Heavy Cream DIETARY_SUPPLEMENT

100 ml of dairy cream with 40.4g of total fat, to ingest orally

Intervention

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• 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).
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Sponsors & Collaborators

• University of Washington: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

University of Washington Medical Center

Seattle, Washington, 98195, United States

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Condition Hierarchy (Ancestors)

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

Study Officials

• Angela J Hanson, MD

  University of Washington

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Angela J Hanson, MD

CONTACT

206-897-5393; hansonlab@uw.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, School of Medicine

Model Details: Each participant undergoes the same intervention

Study Record Dates

• First Submitted: November 19, 2020
• First Posted: December 31, 2020
• Study Start: May 1, 2021
• Primary Completion: June 30, 2025
• Study Completion: December 31, 2025
• Last Updated: May 24, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)