Time-Restricted Eating for Alzheimer's Disease

(TREAD Trial)

Overseen By Olivia Ott, M.S.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of California, San Diego

Must not be taking: Insulin, GLP-1 agonists

Disqualifiers: Neurodegenerative conditions, Diabetes, Disordered eating, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to learn if restricting the time of eating to allow for prolonged fasting at night may reduce sleep disturbances, cognitive decay, and pathology in patients diagnosed with Mild Cognitive Impairment (MCI) or early to moderate Alzheimer's disease (AD). It will also learn about the feasibility of practicing 14 h of nightly fasting in this group of older adults. The main questions it aims to answer are: * Does prolonged nightly fasting of 14 h can reduce markers of AD pathology and aging and reduce cognitive and sleep alterations in MCI and AD patients? * Can patients with MCI and early /moderate AD sustain time-restricted eating for 3 to 6 months? Researchers will compare participants who fast for 14 h per night during 3 months to those who fast for less than 12 h/night. Researchers will also compare participants that fast for 3 months to those who fast during 6 months, to determine the effective duration of the intervention. Finally, researchers will evaluate whether following the time-restricted eating diet alongside a partner actively following the same diet, will increase adherence to the protocol compared to subjects that fast alone. Participants will: * Fast for 14 h a night (stop eating at 8 pm and start eating the following morning at 10 am) for 3 or 6 months * Visit the clinic three times (at the beginning of the study, 6 and 12 months later) * Provide blood samples and take a cognitive test during clinic visits * Keep a diary (or use an app on a smart phone) to record time of eating * Wear an activity tracker watch

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have started a new medication for MCI/AD or changed doses in the last three months, or if you are taking medications that affect appetite.

Is time-restricted eating safe for humans?

Time-restricted eating (TRE) has been studied in both animals and humans, showing potential benefits for brain health and metabolism. While animal studies suggest positive effects, human studies have varied results, and more research is needed to fully understand its safety and effects in people. ^{1 2 3 4 5}

How is time-restricted eating different from other treatments for Alzheimer's disease?

Time-restricted eating (TRE) is unique because it focuses on aligning eating patterns with the body's natural circadian rhythms, which are often disrupted in Alzheimer's disease. Unlike traditional treatments that may target specific symptoms or use medications, TRE aims to improve overall brain health by reducing amyloid deposition and enhancing memory through a structured eating schedule without changing calorie intake. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment Time-Restricted Eating for Alzheimer's Disease?

Research in mice shows that time-restricted feeding can improve memory and reduce brain changes associated with Alzheimer's, like amyloid deposits. In humans, eating fewer meals a day is linked to lower levels of amyloid in the brain, which is a hallmark of Alzheimer's. ^{1 2 6 8 9}

Who Is on the Research Team?

Paula Desplats, PhD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with Mild Cognitive Impairment or early to moderate Alzheimer's Disease who are interested in trying a time-restricted eating pattern. Participants will need to fast for 14 hours nightly and be willing to visit the clinic three times, provide blood samples, take cognitive tests, and track their eating habits.

Inclusion Criteria

I am 65 years old or older.

Ability and willingness to complete cognitive evaluations, blood draw, actigraphy monitoring, and record fasting times daily

In good general health or diagnosed with clinical diagnosis of MCI/AD meeting research consensus criteria

Exclusion Criteria

I have a neurodegenerative condition that is not mild cognitive impairment or Alzheimer's disease.

I have been diagnosed with diabetes.

My cognitive issues are not caused by Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a time-restricted eating regimen with 14 hours of nightly fasting for 3 or 6 months

6 months

3 visits (in-person) at baseline, 3 and 6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

1 visit (in-person) at 12 months

Delayed-Start Intervention

Participants continue their regular eating schedule for 3 months, then start the time-restricted eating intervention for the next 3 months

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Time Restricted Eating

Trial Overview The study is testing if fasting for 14 hours each night can reduce symptoms of Alzheimer's Disease like sleep problems and memory loss. It compares people who fast less than 10 hours with those who do it for longer periods (6 or 12 months) and checks if having a partner doing the same helps stick to the diet.

How Is the Trial Designed?

Group I: Delayed-Start Intervention Active Control 1 Intervention

Participants will continue their regular eating schedule (nightly fasting for less than 12 h) during the first 3 months and start time-restricted eating intervention ( 14 h of nightly fasting) for the next 3 months.

Group II: Intervention Active Control 1 Intervention

Participants will follow the time-restricted regimen (14 h of nightly fasting) for 6 months.

Who Is Running the Clinical Trial?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

A combination of glucagon-like peptide-1 (GLP-1) treatment and time-restricted feeding (TRF) significantly improved circadian rhythms in transgenic Alzheimer's disease (AD) mice, affecting their activity-rest cycles, feeding patterns, and hormone secretion.

This dual treatment not only enhanced metabolic homeostasis and cognitive functions in the mice but also positively influenced the expression of key clock genes and reduced neurodegeneration and neuroinflammation, suggesting a potential therapeutic strategy for managing AD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resetting the circadian clock of Alzheimer's mice via GLP-1 injection combined with time-restricted feeding. Dong, Y., Cheng, L., Zhao, Y.[2022]

Time-restricted feeding (TRF) without caloric restriction significantly improved various aspects of Alzheimer's disease in two transgenic mouse models, including reducing amyloid deposition and enhancing memory.

TRF also normalized daily gene transcription patterns related to Alzheimer's and neuroinflammation, suggesting it could be a promising, accessible intervention to slow down or halt the progression of the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease. Whittaker, DS., Akhmetova, L., Carlin, D., et al.[2023]

In a study of 411 non-demented older adults, those who had low meal frequency (less than three meals a day) showed significantly lower levels of beta-amyloid deposition in the brain, which is associated with Alzheimer's disease pathology.

The research also found that lower meal frequency was linked to higher levels of serum ghrelin, suggesting that this hunger-related hormone may mediate the relationship between meal frequency and reduced amyloid deposition, potentially lowering the risk of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of low meal frequency with decreased in vivo Alzheimer's pathology. Kim, JW., Byun, MS., Yi, D., et al.[2022]

In a study of 32 seniors with probable Alzheimer's disease, behavioral deterioration, particularly psychomotor disturbances like irritability and agitation, was linked to unhealthy eating patterns that favored carbohydrates over proteins, increasing the risk of inadequate protein intake.

Despite cognitive function not predicting breakfast intake, those with greater functional deterioration had lower overall energy intake, suggesting that behavioral changes may significantly impact nutritional health in Alzheimer's patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral disturbances, not cognitive deterioration, are associated with altered food selection in seniors with Alzheimer's disease. Greenwood, CE., Tam, C., Chan, M., et al.[2019]

Intermittent fasting (IF) methods, such as alternate day fasting and time-restricted feeding, were studied in animal models of Alzheimer's disease, showing mixed results on β-amyloid levels, with two studies indicating a reduction in these harmful proteins.

Due to the conflicting findings and variations in study designs, more longitudinal research is needed to determine the effectiveness of intermittent fasting as a preventative strategy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer's Disease: A Scoping Review. Nasaruddin, ML., Syed Abd Halim, SA., Kamaruzzaman, MA.[2021]

Time-restricted feeding (TRF) has shown protective effects against neurodegeneration in two different mouse models of Alzheimer's disease, suggesting it may help synchronize circadian rhythms disrupted in this condition.

The study highlights potential mechanisms by which TRF could benefit brain health, indicating a promising area for further research in Alzheimer's disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Time-restricted feeding and Alzheimer's disease: you are when you eat. King, MW., Chen, Y., Musiek, ES.[2023]

Pharmacological treatments for Alzheimer's disease have been largely ineffective, but multimodal strategies like diet, exercise, and cognitive training show promise in prevention and treatment.

Diets such as the Mediterranean, DASH, and MIND diets, which are rich in neuroprotective compounds, may help protect the brain and prevent Alzheimer's disease, while intermittent fasting and calorie restriction have been linked to improvements in brain health and cognitive function in animal models.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrients in the Prevention of Alzheimer's Disease. Cremonini, AL., Caffa, I., Cea, M., et al.[2020]

Time-restricted eating (TRE) has shown promising therapeutic effects in rodent studies, particularly in relation to body weight and metabolic health, but results in humans are inconsistent due to varying study designs and populations.

This review highlights the need for more standardized research on TRE in humans to better understand its effects and interactions with circadian biology, as well as to identify gaps in current knowledge for future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complex physiology and clinical implications of time-restricted eating. Petersen, MC., Gallop, MR., Flores Ramos, S., et al.[2023]

A study involving 34 nursing home residents with probable Alzheimer's disease showed that replacing traditional dinners with high-carbohydrate meals significantly increased overall food intake, particularly at dinner.

The increase in food consumption was linked to a shift in preference for carbohydrates, especially in individuals with cognitive and behavioral challenges, although those with low body mass indices were less responsive to this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, crossover trial of high-carbohydrate foods in nursing home residents with Alzheimer's disease: associations among intervention response, body mass index, and behavioral and cognitive function. Young, KW., Greenwood, CE., van Reekum, R., et al.[2019]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Resetting the circadian clock of Alzheimer's mice via GLP-1 injection combined with time-restricted feeding. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Association of low meal frequency with decreased in vivo Alzheimer's pathology. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Behavioral disturbances, not cognitive deterioration, are associated with altered food selection in seniors with Alzheimer's disease. [2019]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer's Disease: A Scoping Review. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Time-restricted feeding and Alzheimer's disease: you are when you eat. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Nutrients in the Prevention of Alzheimer's Disease. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Complex physiology and clinical implications of time-restricted eating. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

A randomized, crossover trial of high-carbohydrate foods in nursing home residents with Alzheimer's disease: associations among intervention response, body mass index, and behavioral and cognitive function. [2019]