Alzheimer's Disease; DementiaNCT03070535
APOE Genotype and Diet Influences on Alzheimer's Biomarkers
A study testing HIGH and LOW meal ingestion in people with Alzheimer's Disease; Dementia, run by University of Washington at 1 site in United States.
Trial summary
This study involves the collection of cognitive and biomarker responses to HIGH and LOW meals in healthy older adults with and without the APOE E4 genotype. Subjects will eat the meal after an overnight fast, followed by cognitive testing, spinal fluid and blood collection. Read more about this study
- Who is it for?
- Ages 55 years and olderHealthy volunteers can take part
- Conditions the study is for
- Alzheimer's Disease; Dementia
- What is being tested?
- HIGH and LOW meal ingestion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 78 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2016to 30 Mar 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Written consent is signed and dated by the subject.
- Subject is at least 55 years of age or older, and if female, must be post-menopausal for at least one year, or be one year out from a hysterectomy.
- Able to read and understand English
- Be free of dementia, and able to cognitively and physically give informed consent.
- In the opinion of the investigator, the subject will be able to complete the study procedures.
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Who cannot join
- Diabetes: Known type 1 or Type 2 diabetes, currently taking diabetic medications or insulin, and/or fasting blood glucose ≥ 126 as per the 2009 American Diabetes Association guidelines. Remote use of diabetic agents, or a history of gestational diabetes, is ok.
- Liver and kidney disease: Active liver disease will be excluded. Also excluded are elevations in liver function tests of SGOT (AST) and/or SGPT (ALT) > 1.5 times the upper limit of normal. Active renal disease (Stage IV or V chronic kidney disease) will also be excluded.
- Lipid abnormalities: Diagnosis of hyperlipidemia or hypertriglyceridemia requiring statin, bile acid resins, fibrate medications, and/or high dose niacin will be excluded, as these medications may interfere with the study outcomes. If subjects are on omega-3 fatty acids, low dose niacin, or other alternative/herbal remedies such as red yeast rice, they can be enrolled if they agree to stop the medication during the study period. Also excluded are significant cholesterol abnormalities as defined by the Adult Treatment Panel III classification: LDL cholesterol ≥190 mg/dL, total cholesterol ≥240 mg/dL, or triglycerides > 200. 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.
- Contraindications to lumbar puncture: Those with medical conditions that preclude a lumbar puncture such as an intracranial tumor, lower spinal hardware, or use of anticoagulation, will be excluded. Daily aspirin for prevention is ok. Use of NSAIDS is ok as long as participant uses them as needed rather than daily, and is able to discontinue these agents two days prior to the LP procedures.
- Significant medical illnesses: Illnesses which would cause a hardship on the participant to attend study visits and undergo a lumbar puncture. This includes uncontrolled severe hypertension, unstable angina or cardiovascular disease, moderate pulmonary disease (COPD), and Class III-IV congestive heart failure (CHF).
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- Active malignancy undergoing treatment with chemotherapeutic or radiation treatments. Remote history of treated cancer is ok, as long as current cognition and digestion are not affected
- Treatment with hormones: Use of estrogen, testosterone, and continuous corticosteroid replacements will be excluded, as these may have effects on study outcomes. Women must be post-menopausal for at least 1 year before enrolling in the study, or be one year out from a hysterectomy. Women who use hormone replacement therapy for symptomatic menopause can be enrolled, if they agree to discontinue the medication four weeks before the first meal and then throughout the study. Transgendered subjects can be included in the study, provided that they are not taking sex steroids.
- Psychiatric disorders: Subjects who report active untreated major depression, psychosis, or mania, or who present with those symptoms at the baseline visit, will be excluded. Psychiatric conditions such as post-traumatic stress disorder (PTSD), depression, and anxiety which are stable and treated with medication or therapy are ok.
- Major digestive disorders including inflammatory bowel diseases, irritable bowel syndrome, and celiac disease. History of surgical procedures which may affect the absorption of meals, such as any weight loss surgery such as gastric bypass or banding, or small intestine resection. Acid reflux is allowed if participant is on a stable medication regimen.
- Food allergies and intolerances: Those subjects allergic to the ingredients of the meals will be excluded. Also excluded are medical conditions requiring strict adherence to a particular diet, such as celiac disease or phenylketonuria.
- Alcohol use: While they are in the study, subjects will be asked to limit their alcohol intake to two drinks per day or less for men, or one drink per day or less for women, due to alcohol's effects on lipid biochemistry and the study outcomes. Subjects who are unable or unwilling to meet these criteria will not be enrolled.
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Trial locations and contacts
1 site in 1 country.
United States1 site
University of Washington Medical Center
Seattle, Washington, 98195
About this study
This study involves the collection of cognitive and biomarker responses to HIGH and LOW meals in healthy older adults with and without the APOE E4 genotype. Subjects will eat the meal after an overnight fast, followed by cognitive testing, spinal fluid and blood collection. The HIGH meal will be a meal high in saturated fat and high glycemic index foods vs. LOW meal which will be low in saturated fat and low glycemic index foods.
Read the detailed description
The purpose of this study is to examine how the risk gene for Alzheimer's disease APOE epsilon 4 (E4) influences acute cognitive responses to different types of meals. The rationale for this study is that we know that a diet high in saturated fat and high glycemic index foods (HIGH diet) is a risk factor for Alzheimer's disease (AD). However we have found paradoxically that a Western style HIGH diet acutely improved cognition in APOE E4 carriers, but worsened cognition in E4 non-carriers. This experiment will examine mechanisms that underlie this differential response between E4 carriers and non-carriers.
We will enroll older adults who do not have dementia, half of which will be E4 carriers and the other half will be non-carriers. Both groups will contain equal numbers of men and women. These individuals will undergo two experiments in which they eat either a high or a low fat meal, and then after the meal will undergo several tests. The outcome measures include blood measures of metabolic markers, cognitive tests that are known to be sensitive to changes even after a single meal, and spinal fluid measures of Alzheimer's biomarkers such as beta-amyloid, as well as spinal fluid levels of lipids, glucose and insulin. This study will allow us to test whether high and low fat meals acutely affect cognitive and Alzheimer's biomarkers, and if those changes depend on APOE genotype or gender. It is our hope that this work will contribute to our broader understanding about the risks of diet and AD, to help us understand more about how to prevent and treat this devastating neurological disease.
- Conditions
- Alzheimer's Disease; Dementia
- Being tested
- HIGH and LOW meal ingestion
- Keywords
- APOE E4; cognition; metabolic markers; beta-amyloid
- Medical subject headings
- Alzheimer Disease, Dementia, Plaque, Amyloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIGH and LOW meal ingestionOther
The study will examine CSF biomarker responses to HIGH and LOW meals in 80 men and women with and without the E4 allele in a cross-over design. After an overnight fast, participants will ingest either a HIGH or LOW meal on separate days 3-5 weeks apart in random order. Three hours after meal ingestion, participants will undergo a cognitive battery, followed by spinal fluid collection. Blood samples will also be taken at 7 time points before and after meal ingestion.
| Study group | Role | What they receive |
|---|---|---|
| HIGH meal | Experimental | The HIGH meal is a 700 calorie breakfast style meal, with 50% total fat (25% saturated fat), 30% carbohydrates with a glycemic index of >70, and 20% protein. Receives: Other: HIGH and LOW meal ingestion |
| LOW meal | Experimental | The LOW meal is a 700 calorie breakfast style meal, with 25% of those calories coming from fat (5% saturated fat), 55% carbohydrate (with a glycemic index of <55), and 20% protein. Receives: Other: HIGH and LOW meal ingestion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lipid biomarkers
Paired serum and cerebrospinal fluid levels of free fatty acids and triglycerides
Measured: 4 hours post meal
APOE lipidation
Cerebrospinal fluid levels of total ApoE, and lipidated ApoE
Measured: 4 hours post meal
Insulin
Paired serum and cerebrospinal fluid levels of insulin
Measured: 4 hours post meal
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study startSep 2016
- Primary completion30 Mar 2023
- Study completion30 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Alzheimer's Disease; DementiaStudies of the same condition, open and under way.
- More trials run by University of WashingtonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Subjects will be randomized to receive either the LOW or HIGH meal for their first meal and will cross-over and receive the alternate meal for their next meal. Meals are on separate days.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 78 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Washington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Angela Hanson, University of Washington
- Investigators
- Angela J Hanson, MD, Principal investigator, University of Washington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03070535
- Sponsor's protocol ID
- STUDY00001483
- Status last verified
- Mar 2024
- First submitted
- 27 Feb 2017
- Last updated
- 13 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- APOE Genotype and Diet Influences on Alzheimer's Biomarkers
- ClinicalTrials.gov ID
- NCT03070535
- Acronym / sponsor ID
- STUDY00001483
- Conditions
- Alzheimer's Disease; Dementia
- Keywords
- APOE E4; cognition; metabolic markers; beta-amyloid
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 78 participants (actual)
- Lead sponsor
- University of WashingtonUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- 30 Mar 2023 (actual)
- Study completion
- 30 Mar 2023 (actual)
- First posted
- 3 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study involves the collection of cognitive and biomarker responses to HIGH and LOW meals in healthy older adults with and without the APOE E4 genotype. Subjects will eat the meal after an overnight fast, followed by cognitive testing, spinal fluid and blood collection. The HIGH meal will be a meal high in saturated fat and high glycemic index foods vs. LOW meal which will be low in saturated fat and low glycemic index foods.
Detailed description
The purpose of this study is to examine how the risk gene for Alzheimer's disease APOE epsilon 4 (E4) influences acute cognitive responses to different types of meals. The rationale for this study is that we know that a diet high in saturated fat and high glycemic index foods (HIGH diet) is a risk factor for Alzheimer's disease (AD). However we have found paradoxically that a Western style HIGH diet acutely improved cognition in APOE E4 carriers, but worsened cognition in E4 non-carriers. This experiment will examine mechanisms that underlie this differential response between E4 carriers and non-carriers.
We will enroll older adults who do not have dementia, half of which will be E4 carriers and the other half will be non-carriers. Both groups will contain equal numbers of men and women. These individuals will undergo two experiments in which they eat either a high or a low fat meal, and then after the meal will undergo several tests. The outcome measures include blood measures of metabolic markers, cognitive tests that are known to be sensitive to changes even after a single meal, and spinal fluid measures of Alzheimer's biomarkers such as beta-amyloid, as well as spinal fluid levels of lipids, glucose and insulin. This study will allow us to test whether high and low fat meals acutely affect cognitive and Alzheimer's biomarkers, and if those changes depend on APOE genotype or gender. It is our hope that this work will contribute to our broader understanding about the risks of diet and AD, to help us understand more about how to prevent and treat this devastating neurological disease.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Subjects will be randomized to receive either the LOW or HIGH meal for their first meal and will cross-over and receive the alternate meal for their next meal. Meals are on separate days.
| Arm | Type | Receives |
|---|---|---|
| HIGH meal | Experimental | Other: HIGH and LOW meal ingestionThe HIGH meal is a 700 calorie breakfast style meal, with 50% total fat (25% saturated fat), 30% carbohydrates with a glycemic index of >70, and 20% protein. |
| LOW meal | Experimental | Other: HIGH and LOW meal ingestionThe LOW meal is a 700 calorie breakfast style meal, with 25% of those calories coming from fat (5% saturated fat), 55% carbohydrate (with a glycemic index of <55), and 20% protein. |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Written consent is signed and dated by the subject.
- Subject is at least 55 years of age or older, and if female, must be post-menopausal for at least one year, or be one year out from a hysterectomy.
- Able to read and understand English
- Be free of dementia, and able to cognitively and physically give informed consent.
- In the opinion of the investigator, the subject will be able to complete the study procedures.
Key exclusion criteria (13 listed)
- Diabetes: Known type 1 or Type 2 diabetes, currently taking diabetic medications or insulin, and/or fasting blood glucose ≥ 126 as per the 2009 American Diabetes Association guidelines. Remote use of diabetic agents, or a history of gestational diabetes, is ok.
- Liver and kidney disease: Active liver disease will be excluded. Also excluded are elevations in liver function tests of SGOT (AST) and/or SGPT (ALT) > 1.5 times the upper limit of normal. Active renal disease (Stage IV or V chronic kidney disease) will also be excluded.
- Lipid abnormalities: Diagnosis of hyperlipidemia or hypertriglyceridemia requiring statin, bile acid resins, fibrate medications, and/or high dose niacin will be excluded, as these medications may interfere with the study outcomes. If subjects are on omega-3 fatty acids, low dose niacin, or other alternative/herbal remedies such as red yeast rice, they can be enrolled if they agree to stop the medication during the study period. Also excluded are significant cholesterol abnormalities as defined by the Adult Treatment Panel III classification: LDL cholesterol ≥190 mg/dL, total cholesterol ≥240 mg/dL, or triglycerides > 200. 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.
- Contraindications to lumbar puncture: Those with medical conditions that preclude a lumbar puncture such as an intracranial tumor, lower spinal hardware, or use of anticoagulation, will be excluded. Daily aspirin for prevention is ok. Use of NSAIDS is ok as long as participant uses them as needed rather than daily, and is able to discontinue these agents two days prior to the LP procedures.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIGH and LOW meal ingestionThe study will examine CSF biomarker responses to HIGH and LOW meals in 80 men and women with and without the E4 allele in a cross-over design. After an overnight fast, participants will ingest either a HIGH or LOW meal on separate days 3-5 weeks apart in random order. Three hours after meal ingestion, participants will undergo a cognitive battery, followed by spinal fluid collection. Blood samples will also be taken at 7 time points before and after meal ingestion. | Other | HIGH meal, LOW meal |
Primary outcome
Lipid biomarkers
Time frame: 4 hours post meal
Paired serum and cerebrospinal fluid levels of free fatty acids and triglycerides
APOE lipidation
Time frame: 4 hours post meal
Cerebrospinal fluid levels of total ApoE, and lipidated ApoE
Insulin
Time frame: 4 hours post meal
Paired serum and cerebrospinal fluid levels of insulin
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2024.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Angela J Hanson, MD principal investigator
University of Washington
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HIGH and LOW meal ingestion in people with Alzheimer's Disease; Dementia, run by University of Washington at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Lipid biomarkers (time frame: 4 hours post meal). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Mar 2024.