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?

This trial explores whether fasting for 14 hours each night (known as Time-Restricted Eating) can improve sleep, memory, and brain health in individuals with early Alzheimer's disease or mild cognitive impairment. Participants will fast overnight for either 3 or 6 months and visit the clinic three times for tests and check-ins. The trial will also assess whether having a fasting partner makes adherence easier. Individuals diagnosed with mild cognitive issues related to Alzheimer's who currently fast less than 12 hours at night might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to explore this innovative approach.

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.

What prior data suggests that time-restricted eating is safe for individuals with Alzheimer's disease?

Research has shown that time-restricted eating, which involves not eating for certain hours each day, is generally safe and easy for most people to follow. Studies have found that fasting for 16 hours is safe for older adults, and many adapt to it easily.

Research also suggests that this eating pattern can enhance thinking skills in people with Alzheimer's disease, particularly in planning and decision-making. Early evidence hints that it might protect the brain and reduce inflammation related to Alzheimer's.

Overall, current research supports time-restricted eating as a safe method to boost brain health, especially for older adults. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about time-restricted eating for Alzheimer's disease because it offers a fresh approach that diverges from traditional medication-based treatments. Unlike drugs that primarily target brain chemistry to manage symptoms, this method focuses on metabolic health by extending the overnight fasting period to 14 hours. This approach could potentially improve brain function and delay disease progression by optimizing the body's natural rhythm and reducing inflammation. By exploring this dietary strategy, scientists hope to uncover a non-pharmacological way to impact Alzheimer's disease positively, offering a new avenue for managing this challenging condition.

What evidence suggests that time-restricted eating could be an effective treatment for Alzheimer's disease?

Research shows that time-restricted eating, which involves eating only during certain hours, might improve brain function in people with Alzheimer's disease. Studies have found that this method can enhance skills like planning and decision-making. In this trial, participants in one arm will follow a time-restricted regimen (14 hours of nightly fasting) for 6 months. Another study discovered that time-restricted eating can improve the disease's effects and daily routines without requiring calorie reduction. It has proven safe and easy for older adults to adapt to. Overall, these findings suggest that time-restricted eating could help manage Alzheimer's disease symptoms. ^{1 3 4 5 6}

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

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

I am 65 years old or older.

For cognitively normal living partners in the dyads group, scores greater than 26 in the Montreal Cognitive Assessment (MoCA) test administered at screening

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

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]

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]

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]

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5388543/

Fasting, circadian rhythms, and time restricted feeding in ... Seven months of FMD cycles also resulted in improvements in a battery of behavioral tests ranging from motor coordination, to long and short-term memory ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1550413123002735

Circadian modulation by time-restricted feeding rescues ... We show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, ...

3. alzdiscovery.org alzdiscovery.org/uploads/cognitive_vitality_media/Time_restricted_eating.pdf

Time restricted eating Time-restricted feeding has been shown to slow tumor growth and restore circadian rhythms in preclinical models [61], however, not all tumor types appear to be ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06429124

Time Restricted Eating in Alzheimer's Disease Previous research has shown that 16 hours of fasting is feasible, safe and well-tolerated among older adults, and that most persons report easy adjustment ( ...

5. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/imt2.70006

Time‐restricted feeding mitigates Alzheimer's disease ... Time-restricted feeding (TRF) improved cognitive function in Alzheimer's disease (AD) patients, with notable enhancement in executive function.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0531556522003424

The effects of time-restricted eating on sleep, cognitive ... Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans.