Time Restricted Eating in Alzheimer's Disease

Official title

Time-Restricted Eating in Alzheimer's Disease : The T.R.E.A.D Trial

Overview

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.

Detailed description

The goal of this pilot study on time restricted eating regimens in the mild cognitive impairment (MCI) patient population will be to determine the feasibility of implementing the intervention and impact of time-restricted eating on cognitive performance and biomarkers of metabolic health. Researchers at the Barrow Neurological Institute, Alzheimer\'s Disease Program in collaboration with the Arizona State University College of Health Solutions will execute the specific aims using a pre-post non-randomized study design in which all participants receive the intervention. Outcome assessments for specific aim 2 will include neuropsychological tests, blood biomarkers, and psychological well-being measured at baseline and after 3 months of 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. Primary outcomes will include participant recruitment, retention, acceptability, safety, and adherence to the 16 hours of fasting and 8-hour eating window. Researchers hypothesize that participants who follow a time-restricted eating pattern will have improvements in attention, working memory and semantic fluency domains. Study staff hypothesize that there will be improvements or trends toward improvements in inflammatory and cardiometabolic biomarkers (i.e., interleukin-6, tumor necrosis factor alpha, C-reactive protein, insulin, hemoglobin A1c, and lipids).

The results of this project will provide critical preliminary data for a longer-term, large-scale, randomized controlled trial of time-restricted eating on cognitive trajectory among adults with MCI. The novel findings from the proposed project and future studies will contribute significantly to the body of knowledge that will advance the field, with the ultimate goal of preventing or delaying the progression of MCI to dementia.

Interventions

• Behavioral Dietary 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 extensi

Primary outcome measures

• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Average number of days per week of time-restricted eating [Time frame: The eating window is assessed daily throughout the 3-month intervention.]

Secondary outcome measures (12)

• Physical Activity and Sedentary Behavior Questionnaire Score [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Memory as measured by the Comprehensive TrailMaking Test (CTMT) [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Cognitive Impairment as measured by the Mini Mental State Examination (MMSE) [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Verbal Memory as Measured by the Auditory VerbalLearning Test (AVLT) [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Working Memory as measured by the WAIS-IV Digit Span Forward/Backward [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Psychological Flexibility as Measured by the Comprehensive Assessment of Acceptance and Commitment Therapy Process (CompACT) [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Brief Resilience Scale (BRS) Score [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Perceived Stress Scale (PSS) Score [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Pittsburgh Sleep Quality Index (PSQI) Score [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• WHO Quality of Life Questionnaire [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]
• Hemoglobin A1c [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention)]
• C-reactive protein [Time frame: Will be assessed at baseline (pre-intervention) and after the 3-month intervention (post-intervention).]

Eligibility criteria

Inclusion criteria

• Male or Female outpatients 55-89 years of age.
• Meet Mayo Clinic Criteria for MCI.
• If taking medications that may affect one or more study outcome measures(such as donepezil and memantine),the participant must be on a stable dose for at least the preceding 3 months.
• A body mass index ≥18.5 and <40.0 kg/m2.
• Access to the internet through computer or smartphone.
• Must have a collateral informant/study partner(e.g. spouse or adult child) who has significant direct contact with the patient and who is willing to accompany the patient to specified clinic visits and be available for telephone visits/Interviews.
• An education level > 8 years.
• A 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.
• Vision and hearing must be sufficient to comply with study procedures.

Exclusion criteria

• Diabetes mellitus that requires insulin treatment or is not well managed.
• An eating disorder.
• A contraindication to time-restricted eating.
• Daily eating window <11 hours/day on ≥3 days/week.
• MMSE score ≤9 or patients diagnosed with severe dementia by a clinician.
• In the opinion of the investigator, participation would not be in the best interest of the subject.
• Taking prescription medications twice a day that need to be taken with food.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

United States · 2 centers

• Arizona State University, College of Health Solutions — Phoenix
• Barrow Neurological Institute, Division of Alzheimer's Disease — Phoenix

Publications

• Anson RM, Guo Z, de Cabo R, Iyun T, Rios M, Hagepanos A, Ingram DK, Lane MA, Mattson MP. Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake. Proc Natl Acad Sci U S A. 2003 May 13;100(10):6216-20. doi: 10.1073/pnas.1035720100. Epub 2003 Apr 30. PMID 12724520
• Anton SD, Lee SA, Donahoo WT, McLaren C, Manini T, Leeuwenburgh C, Pahor M. The Effects of Time Restricted Feeding on Overweight, Older Adults: A Pilot Study. Nutrients. 2019 Jun 30;11(7):1500. doi: 10.3390/nu11071500. PMID 31262054
• Anton SD, Moehl K, Donahoo WT, Marosi K, Lee SA, Mainous AG 3rd, Leeuwenburgh C, Mattson MP. Flipping the Metabolic Switch: Understanding and Applying the Health Benefits of Fasting. Obesity (Silver Spring). 2018 Feb;26(2):254-268. doi: 10.1002/oby.22065. Epub 2017 Oct 31. PMID 29086496
• Brookmeyer R, Gray S, Kawas C. Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset. Am J Public Health. 1998 Sep;88(9):1337-42. doi: 10.2105/ajph.88.9.1337. PMID 9736873
• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4. PMID 2748771
• Carlson AJ, Hoelzel F. Apparent prolongation of the life span of rats by intermittent fasting. J Nutr. 1946 Mar;31:363-75. doi: 10.1093/jn/31.3.363. No abstract available. PMID 21021020
• Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983 Dec;24(4):385-96. No abstract available. PMID 6668417
• Dimitratos SM, German JB, Schaefer SE. Wearable Technology to Quantify the Nutritional Intake of Adults: Validation Study. JMIR Mhealth Uhealth. 2020 Jul 22;8(7):e16405. doi: 10.2196/16405. PMID 32706729

Identifiers

NCT: NCT06429124 · HX-23-500-347-30-03

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗