Time-Restricted Eating for Alzheimer's Disease
(TREAD Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: University of California, San Diego
Must not be taking: Insulin, GLP-1 agonists
Disqualifiers: Neurodegenerative conditions, Diabetes, Disordered eating, others
No Placebo Group
Trial Summary
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.
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.
12345Is 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.
23678How 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.
12369Eligibility Criteria
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
+2 more
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.
+6 more
Trial Timeline
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
Participant Groups
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.
2Treatment groups
Active Control
Group I: Delayed-Start InterventionActive Control1 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: InterventionActive Control1 Intervention
Participants will follow the time-restricted regimen (14 h of nightly fasting) for 6 months.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Shiley Marcos Alzheimer's Disease CenterSan Diego, CA
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Who Is Running the Clinical Trial?
University of California, San DiegoLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Resetting the circadian clock of Alzheimer's mice via GLP-1 injection combined with time-restricted feeding. [2022]Circadian rhythm disturbances are the most common symptoms during the early onset of AD. Circadian rhythm disorders aggravate the deposition of amyloid plaques in the brains of AD patients. Therefore, improving the circadian rhythm of AD patients might slow down the pathological development of neurodegeneration. Circadian regulation is driven by a master clock in suprachiasmatic nuclei (SCN) and peripheral clock located in peripheral organs. The rhythmic feeding-fasting cycle has been proved to dominant cue to entrain peripheral clocks. We hypothesized that dietary intervention to a certain period of time during the dark phase might entrain the clock and reset the disrupted daily rhythms of AD mice. In this study, exogenous glucagon-like peptide-1 (GLP-1) treatment, time-restricted feeding (TRF), and the combination were used to examine the effect of overall circadian rhythm and neurodegenerative pathogenesis of transgenic AD mice. It was confirmed that GLP-1 administration together with time-restricted feeding improves circadian rhythm of 5 × FAD mice including the physiological rhythm of the activity-rest cycle, feeding-fasting cycle, core body temperature, and hormone secretion. Furthermore, GLP-1 and TRF treatments improved the diurnal metabolic homeostasis, spatial cognition, and learning of 5 × FAD mice. The aberrant expression of clock genes, including Baml1, Clock, and Dbp, was improved in the hypothalamus, and pathological changes in neurodegeneration and neuroinflammation were also observed in AD mice with dual treatment.
Circadian modulation by time-restricted feeding rescues brain pathology and improves memory in mouse models of Alzheimer's disease. [2023]Circadian disruptions impact nearly all people with Alzheimer's disease (AD), emphasizing both their potential role in pathology and the critical need to investigate the therapeutic potential of circadian-modulating interventions. Here, we show that time-restricted feeding (TRF) without caloric restriction improved key disease components including behavioral timing, disease pathology, hippocampal transcription, and memory in two transgenic (TG) mouse models of AD. We found that TRF had the remarkable capability of simultaneously reducing amyloid deposition, increasing Aβ42 clearance, improving sleep and memory, and normalizing daily transcription patterns of multiple genes, including those associated with AD and neuroinflammation. Thus, our study unveils for the first time the pleiotropic nature of timed feeding on AD, which has far-reaching effects beyond metabolism, ameliorating neurodegeneration and the misalignment of circadian rhythmicity. Since TRF can substantially modify disease trajectory, this intervention has immediate translational potential, addressing the urgent demand for accessible approaches to reduce or halt AD progression.
Association of low meal frequency with decreased in vivo Alzheimer's pathology. [2022]Little is known about the association between meal frequency and Alzheimer's disease (AD) in humans. We tested the hypothesis that low meal frequency (LMF) is associated with reduced in vivo AD pathology in human brain, and additionally investigated the mediation of serum ghrelin, a hunger-related hormone, for the association. A total of 411 non-demented older adults were systematically interviewed to identify their dietary patterns including meal frequency and underwent multi-modal neuroimaging for cerebral beta-amyloid (Aβ) and tau deposition, glucose metabolism, and cerebrovascular injury. LMF (less than three meals a day) was significantly associated with lower Aβ deposition compared to high meal frequency (HMF). In addition, both LMF and reduced Aβ deposition were significantly related to elevated serum ghrelin. Our findings suggest that LMF may be related to the lower risk of AD through reduced brain amyloid deposition. Additionally, ghrelin appears mediate the association between LMF and lower amyloid deposition.
Behavioral disturbances, not cognitive deterioration, are associated with altered food selection in seniors with Alzheimer's disease. [2019]We previously reported alterations in circadian patterns of food intake that are associated with measures of functional and cognitive deterioration in seniors with probable Alzheimer's disease (AD). This study further explored disturbed eating patterns in AD, focusing on alterations in macronutrient (protein, carbohydrate, and fat) selection, and their association with measures of functional and behavioral losses.
Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer's Disease: A Scoping Review. [2021]We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer's disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords "amyloid beta", "intermittent fasting", "intermittent caloric restriction", "alternate day fasting", "modified alternate-day fasting", "time-restricted feeding", "Ramadan fast", "intermittent calori* restriction", "intermittent restrictive diet", and "Alzheimer*". Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer's disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.
Time-restricted feeding and Alzheimer's disease: you are when you eat. [2023]Time-restricted feeding (TRF) has emerged as a means of synchronizing circadian rhythms, which are commonly disrupted in Alzheimer's disease (AD). Whittaker et al. demonstrate that TRF exerts protective effects in two mouse models of AD. We discuss the effects of TRF on brain health and mechanisms linking TRF to neurodegeneration.
Nutrients in the Prevention of Alzheimer's Disease. [2020]Alzheimer's disease (AD) is a disease caused by the complex interaction of multiple mechanisms, some of which are still not fully understood. To date, pharmacological treatments and supplementation of individual nutrients have been poorly effective in terms of the prevention and treatment of AD, while alternative strategies based on multimodal approaches (diet, exercise, and cognitive training) seem to be more promising. In this context, the focus on dietary patterns rather than on single food components could be more useful in preventing or counteracting the pathological processes typical of AD, thanks to the potential synergistic effects of various nutrients (neuronutrients). The aim of this narrative review is to summarize the currently existing preclinical and clinical evidence regarding the Mediterranean diet (MeDi), the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which are three dietary patterns with well-known anti-inflammatory and antioxidant properties. Recently, they have been related to brain protection and AD prevention, perhaps thanks to their high content of neuroprotective bioactive compounds. Similarly, intermittent fasting (IF) or calorie restriction (CR) is emerging as interesting approaches that seem to promote hippocampal neurogenesis, activate adaptive stress response systems, and enhance neuronal plasticity, thus leading to motor and cognitive improvements in animal models of AD and hopefully also in human beings.
Complex physiology and clinical implications of time-restricted eating. [2023]Time-restricted eating (TRE) is a dietary intervention that limits food consumption to a specific time window each day. The effect of TRE on body weight and physiological functions has been extensively studied in rodent models, which have shown considerable therapeutic effects of TRE and important interactions among time of eating, circadian biology, and metabolic homeostasis. In contrast, it is difficult to make firm conclusions regarding the effect of TRE in people because of the heterogeneity in results, TRE regimens, and study populations. In this review, we 1) provide a background of the history of meal consumption in people and the normal physiology of eating and fasting; 2) discuss the interaction between circadian molecular metabolism and TRE; 3) integrate the results of preclinical and clinical studies that evaluated the effects of TRE on body weight and physiological functions; 4) summarize other time-related dietary interventions that have been studied in people; and 4) identify current gaps in knowledge and provide a framework for future research directions.
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]Despite recognition that weight loss is a problem in elderly persons with probable Alzheimer's disease (AD), increasing their food intake remains a challenge. To effectively enhance intake, interventions must work with individuals' changing needs and intake patterns. Previously, the authors reported greater food consumption at breakfast, a high-carbohydrate meal, compared with dinner, and shifts toward carbohydrate preference at dinner in those with increased behavioral difficulties, low body mass index, or both.