Intermittent Fasting for Alzheimer's Disease

(TREAD Trial)

Recruiting at 1 trial location

Overseen By Geetika Chahal, MBBS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

Disqualifiers: Diabetes, Eating disorder, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the treatment Time Restricted Eating, Time-Restricted Feeding, Intermittent Fasting, Circadian Rhythm-Based Eating for Alzheimer's Disease?

Research shows that time-restricted feeding (eating only during certain hours) can improve memory and reduce harmful brain changes in mice with Alzheimer's. Additionally, eating fewer meals a day is linked to lower levels of brain changes associated with Alzheimer's in humans. ^{1 2 3 4 5}

Is intermittent fasting safe for humans?

Intermittent fasting, including time-restricted feeding, has been studied in animal models and shows potential benefits for brain health, but more research is needed to fully understand its safety and effects in humans. It is generally considered safe for most people, but individuals should consult with a healthcare provider before starting, especially if they have existing health conditions. ^{1 2 3 6 7}

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 pathways, TRE aims to improve overall brain health by reducing amyloid deposition and enhancing memory through synchronized eating schedules. ^{1 2 3 6 8}

What is the purpose of this trial?

This pilot and feasibility study will enable the research team to determine the feasibility of implementing a time-restricted eating regimen among adults with mild cognitive impairment (MCI) and the impact of time-restricted eating on cognitive performance and biomarkers of metabolic health in this population. Study staff will execute the specific aims using a pre-post, non-randomized study design in which all participants receive the intervention. The intervention is a 16/8 time-restricted eating regimen characterized by fasting for 16 hours and eating within an 8-hour window on 5 days per week for 3 months. Assessments will be performed at baseline and after the 3-month time-restricted eating intervention with the following outcome measures. Outcome measures for feasibility include participant recruitment, retention and metrics of acceptability, safety, and adherence to the intervention. Outcome measures for cognitive performance and metabolic health include neuropsychological tests, blood biomarkers, and surveys of psychological well-being.

Research Team

Yonas E Geda, MD, MSc

Principal Investigator

Barrow Neurological Institute, Alzheimer's Disease and Cognitive Disorders Division

Eligibility Criteria

This trial is for adults with mild cognitive impairment (MCI) who may have Alzheimer's. Participants will try a special eating schedule, fasting for 16 hours and only eating within an 8-hour window on weekdays for three months. The study aims to see if this can improve thinking skills and health markers in the blood.

Inclusion Criteria

Meet Mayo Clinic Criteria for MCI

Body mass index >18.5 and <40.0 kg/m2

Proficiency in speaking and reading English or having a family member who is proficient in reading and speaking English and is willing to serve as a translator

Exclusion Criteria

Eating disorder

I have diabetes that needs insulin or is not well-controlled.

Contraindication to time-restricted eating

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a 16/8 time-restricted eating regimen characterized by fasting for 16 hours and eating within an 8-hour window on 5 days per week for 3 months

12 weeks

Individual and group sessions for education, coaching, and support

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Time Restricted Eating

Trial Overview The TREAD study tests a dietary intervention called time-restricted eating, where participants fast daily for 16 hours and eat during an 8-hour period. This non-randomized trial involves all volunteers following the regimen, with assessments before and after the three-month period to measure its impact.

Participant Groups

Group I: Interventional Experimental Treatment 1 Intervention

Participants will be instructed to follow a 16/8 regimen characterized by 16 hours of fasting and an 8-hour eating window daily, on approximately 5 days/week, for 3 months. 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 (Anton, Lee et al. 2019, Lee, Sypniewski et al. 2020). The intervention will be implemented through individual and group sessions with participants and will involve extensive education, coaching, guidance, and support throughout the 3-month intervention. Educational materials on lifestyle factors including physical activity will be provided to each participant. We will be also be collecting data on physical activity and sedentary behavior. These data will be co-variates when we conduct the statistical analysis.

Who Is Running the Clinical Trial?

St. Joseph's Hospital and Medical Center, Phoenix

Lead Sponsor

Trials

69

Recruited

17,400+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

Karlsruhe Institute of Technology

Collaborator

Trials

4

Recruited

510+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Findings from Research

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&#160;vivo Alzheimer's pathology. Kim, JW., Byun, MS., Yi, D., et al.[2022]

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]

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]

Intermittent fasting (IF) has shown potential benefits for brain health and cognitive function, particularly in animal models, but there is currently no clear evidence of short-term cognitive improvements in healthy humans.

Clinical studies suggest that IF may help manage symptoms and progression of brain disorders such as epilepsy, Alzheimer's disease, and multiple sclerosis, indicating its potential as a therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Intermittent Fasting on Brain and Cognitive Function. Gudden, J., Arias Vasquez, A., Bloemendaal, M.[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 feeding can positively influence circadian rhythms, which are often disrupted in Alzheimer's disease, potentially slowing the disease's progression.

The study used mouse models of Alzheimer's to demonstrate that adjusting feeding times can alter the trajectory of the disease, suggesting a new avenue for therapeutic intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restricting mealtime ameliorates neurodegeneration. Tian, X., Sinclair, DA.[2023]

References

1. 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]

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

Association of low meal frequency with decreased in&#160;vivo Alzheimer's pathology. [2022]

3. 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]

4. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

The Effects of Intermittent Fasting on Brain and Cognitive Function. [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

Restricting mealtime ameliorates neurodegeneration. [2023]