Clinical trial NCT06548191: TREAD: Time Restricted Eating Intervention for Alzheimer's Disease
Official title: TREAD: Time Restricted Eating Intervention for Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Alzheimer's Disease
Keywords: Time-Restricted Eating
Intermittent Fasting
Prolonged Nightly Fasting
Mild Cognitive Impairment
Alzheimer Disease
Circadian Rhythms
Cognition
Neuropathology
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2024-08-12
Enrollment: 60
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: TREAD will enroll 40 older adults (60+ years) with cognitive impairment and clinically diagnosed with Mild Cognitive Impairment (MCI) or early to moderate AD; and 20 cognitively normal subjects (18+ years). The investigators will recruit individual participants with a diagnosis of MCI/AD (n=20 subjects) and 20 dyads of participants (n=40 subjects) composed of an MCI/AD patient and a cognitively normal living partner. This design is necessary to evaluate how feasible and burdensome is to follow a time-restricted eating pattern for individuals with cognitive impairment. Individual and dyad participants will be randomized in equal ratios to the complete prolonged nightly fasting intervention (14 h fast with no energy intake after 8 pm for 6 months) or to a delayed-start prolonged nightly fasting intervention (3 initial months of unrestricted eating patterns followed by 3 months of 14 h fast with no energy intake after 8 pm) using a random permuted-block design.
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: Study Description: Our overarching hypothesis is that circadian alignment of food intake and biological clocks can reduce pathology and improve cognitive function in Alzheimer's disease (AD) patients. The rationale for this proposal is that the prolonged nightly fasting form of Time-restricted eating (TRE) aligns food intake with the daytime "wake phase" of the biological clock, optimizing nutrient processing, and may modulate disease trajectory in AD. This Pilot study will test the feasibility and safety of TRE, consisting of 14 hours of night fasting for 3 or 6 months, in patients along the AD continuum and will explore the outcomes of this intervention on markers of aging and AD pathology. Results from this study will provide a strong scientific justification and will optimize the methods for a larger trial to determine the clinical efficacy of TRE to mitigate disease progression in AD and related dementias.

Objectives:

Primary Objective: Test the feasibility of a TRE intervention (TREAD) among patients with Mild Cognitive Impairment (MCI) or AD.

Secondary Objectives: Explore the effects of TRE on metabolic and pathological markers in MCI/AD patients.

Endpoints:

Primary Endpoint: Feasibility, safety, cognition, and metabolic indicators. Secondary Endpoints: Biomarkers of AD pathology, sleep and activity, and markers of epigenetic aging.

Study Population:

Adult subjects (female and males, ≥60 years old) with normal cognition or with a clinical diagnosis of MCI/AD (meeting research consensus criteria for probable MCI or dementia due to AD).

Phase: Early phase 1

Description of Sites/Facilities Enrolling Participants:

Shiley-Marcos Alzheimer's disease Research Center (SMARDC) at the University of California San Diego (UCSD) La Jolla campus.

Description of Study Intervention: The investigators will enroll older-adult participants (\>60 years old) clinically diagnosed with MCI or early to moderate AD (n=20 subjects) and 20 dyads of participants (n=40 subjects) composed of an MCI/AD patient and a cognitively normal living partner (\> 18 years old ); for a total enrollment of 60 subjects. All participants must have a baseline nightly fasting of \<12 h. Individual participants and dyads will be randomized into the Intervention group (INT) or the Delayed Start Intervention group (DS-INT). The intervention will involve prolonged nightly fasting of 14 hours (TRE). The INT group will follow the TRE regimen for 12 months. The DS-INT group will practice their regular eating pattern for 3 months (nightly fasting \<12 h) followed by 3 months of TRE. All participants will have study visits, outcome assessments, and biospecimen collections at baseline, 3, and 6 months.

Study Duration: Two years Participant Duration: 6 months

Eligibility criteria: Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures and availability for the duration of the study.

Inclusion criteria

1. Persons, aged ≥60 years
2. In good general health as evidenced by medical history or diagnosed with clinical diagnosis of MCI/AD: meeting research consensus criteria for probable MCI or dementia due to AD, requiring positive amyloid biomarkers in brain or cerebrospinal fluid (CSF) obtained at their regular point of care or study referral no longer than 3 months prior to screening.
3. Ability and willingness to complete cognitive evaluations, blood draw, actigraphy monitoring and to record fasting times daily.
4. Daily night fasting \<12h at baseline. Ability and willingness to follow an eating protocol of prolonged night fasting for 14 h
5. For cognitively normal living partners in the dyads group, scores \>26 in the Montreal Cognitive Assessment (MoCA) test administered at screening.

Exclusion Criteria:

1. Clinical diagnosis with a neurodegenerative condition other than MCI/AD.
2. Presenting cognitive impairment not due to AD.
3. Clinical diagnoses of diabetes.
4. Actively using insulin in the past 6 months.
5. Started a new medication (or changed doses) indicated for the treatment of MCI/AD in the last three months prior to enrollment.
6. Currently taking any medication known to affect appetite, inlcuding but not limited to GLP-1 agonists.
7. Any history of disordered eating, including difficulty swallowing and refusal to eat.
8. Currently engaged in shift work.
9. In treatment with another investigational drug.
10. Body Mass Index (BMI) \<20. or \>35

Primary outcomes:
measure: Feasibility: assessed by computing the number of nights achieving the goal fasting time of 14 h.
timeFrame: 3 and 6 months
Secondary outcomes:
measure: Effects of TRE on activity rhythms measured as steps/day using an accelerometer
timeFrame: baseline, 3 and 6 months
measure: Effects of TRE on skin temperature rhythms measured in F using a smart sensor.
timeFrame: baseline, 3 and 6 months
measure: Effects of TRE on sleep quantity (as hours/night) using a smart sensor.
timeFrame: Baseline, 3 and 6 months
measure: Effects of TRE on sleep quality (determined by a sleep score) using a smart sensor.
timeFrame: baseline, 3 and 6 months
measure: Explore the effects of TRE on pathology in MCI/AD patients
timeFrame: baseline, 3 and 6 months
measure: Explore the effects of TRE on markers of epigenetic aging by profiling DNA methylation in blood samples.
timeFrame: baseline, 3 and 6 months
measure: Explore the effects of TRE on fasting blood glucose (mg/mL)
timeFrame: baseline, 3 and 6 months
measure: Evaluation of neurocognitive changes using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog).
timeFrame: baseline and 6 months
measure: Evaluation of changes in self-reported sleep quality as determined by the Pittsburgh Sleep Quality Index (PSQI).
timeFrame: baseline, 3 and 6 months
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Shiley Marcos Alzheimer's Disease Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Paula Desplats, PhD
role: PRINCIPAL_INVESTIGATOR
References: