TREAD: Time Restricted Eating Intervention for Alzheimer's Disease
NCT Number: NCT06548191
Acronym: TREAD
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Mild Cognitive Impairment|Alzheimer Disease
Interventions: BEHAVIORAL: Time-restricted eating
Sponsor: University of California, San Diego
Collaborators: National Institute on Aging (NIA)
Sex: ALL
Age: OLDER_ADULT
Enrollment: 60
Study Design: Allocation: RANDOMIZED|Intervention Model: CROSSOVER|Masking: DOUBLE (INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: TREATMENT
Start Date: 2024-08
Completion Date: 2026-02
Locations: Shiley Marcos Alzheimer's Disease Center, San Diego, California, 92093, United States

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 6 to 12 months? Researchers will compare participants who fast for 14 h per night during 6 months to those who fast for less than 10 h/night. Researchers will also compare participants that fast for 6 months to those who fast during 12 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 6 or 12 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

Primary Outcome Measures: Feasibility: assessed by computing the number of nights achieving the goal fasting time of 14 h., Test the feasibility of a Time-restricted eating intervention in patients with MCI or AD by quantification the number of days during the intervention period when the particpants reached the goal intervention fasting time of 14 h, b) increased fasting of \>12 h and \<14 h., 6 and 12 months
Secondary Outcome Measures: Effects of TRE on activity rhythms measured as steps/day using an accelerometer, The investigators will measure the participants' 24-hour activity rhythms using an actigraph unit. The investigators will calculate interday stability and intraday variability of activity rhythms, which have been reported as sensitive in studies on aging and AD cohorts. Interday stability will indicate the stability of rhythms across several days. Intraday variability will indicate the fragmentation of rhythms., baseline, 6 and 12 months|Effects of TRE on skin temperature rhythms measured in F using a Fitbit smart sensor., The investigators will measure the participants' 24-hour temperature rhythms using a smart sensor (Fitbit). The investigators will calculate interday stability and intraday variability of skin temperature as a circadian output., baseline, 6 and 12 months|Effects of TRE on sleep quantity (as hours/night) using a smart sensor., The investigators will determine changes in sleep duration during the study as recorded by a smart sensor and accessed via the Fitabase., Baseline, 6 and 12 months|Effects of TRE on sleep quality (determined by a sleep score) using a smart sensor., The investigators will determine whether the overall sleep efficiency changes based on the sleep score calculated by the Fibit algorithm and accessed via the Fitabase. The overall sleep score is a sum of the individual scores in sleep duration, sleep quality, and restoration, with a maximum of 100. Sleep score tiers are: Excellent: 90-100; Good: 80-89; Fair: 60-79; Poor: Less than 60., baseline, 6 and 12 months|Explore the effects of TRE on pathology in MCI/AD patients, Evaluate levels of amyloid Beta (AB)40, AB42, phospho-Tau181, Neurofilament light chain protein, and markers of neuroinflammation in plasma, baseline, 6 and 12 months|Explore the effects of TRE on markers of epigenetic aging by profiling DNA methylation in blood samples., The investigators will profile genome-wide DNA methylation in whole blood using the Infinium Methylation EPIC v2.0 array (Illumina) to determine whether prolonged fasting modulates epigenetic aging rates. A beneficial effect will result in no changes to the subjects' biological aging rate or a deacceleration of aging., baseline, 6 and 12 months|Explore the effects of TRE on fasting blood glucose (mg/mL), The investigators will measure glucose levels in the blood at the end of fasting during the clinical visits to evaluate whether prolonged fasting reduces fasting glucose as an indicator of metabolic health., baseline, 6 and 12 months|Evaluation of neurocognitive changes using the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog)., The investigators will utilize the ADAS-Cog test to investigate whether TRE reduces cognitive decline in MCI and AD patients, expressed as the average score changes between visits. The ADAS-Cog is a brief neuropsychological assessment tool used to determine the severity of cognitive symptoms of dementia, widely used in clinical trials assessing antidementia treatments. The ADAS-Cog scores range from 0 to 70, with higher scores indicating poorer performance. It consists of 11 tasks, including Word Recall, Naming Objects and Fingers, Following Commands, Constructional Praxis, Ideational Praxis, Orientation, Word Recognition, Remembering Test Directions, Spoken Language, Comprehension, and Word-Finding Difficulty., baseline, 6 and 12 months|Evaluation of changes in self-reported sleep quality as determined by the Pittsburgh Sleep Quality Index (PSQI)., The investigators will utilize the PSQI to investigate whether TRE improves self-reported sleep quality. Each component score of the PSQI ranges from 0 to 3, with 3 indicating the worst dysfunction. The global PSQI score ranges from 0 to 21 and is obtained by adding the scores of the seven components of the test. Higher scores indicate poorer sleep quality, with a score greater than 5 suggesting significant sleep difficulties., baseline, 6 and 12 months