Insomnia in Older Adults: Impact of Personalized, Diet-Induced Alterations in the Microbiota

Study Overview
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Brief Summary
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Insomnia is a chronic mental health condition characterized by difficulty initiating and maintaining sleep with a prevalence of over 50% in Israeli adults ages 65 and above. It is associated with increased risks for chronic illnesses (e.g., cardiovascular disease), poor mental health (e.g., anxiety and depression), functional limitations, and cognitive decline. Available pharmacological and behavioral treatments focusing on reducing nighttime hyper-arousal offer limited success, and it appears that there is no one size fits all treatment for late life insomnia. Mounting evidence suggests that sleep is related to metabolic status, however, studies on the associations between sleep and dietary patterns are surprisingly scarce. The ability of gut microbiota to communicate with the brain is emerging as an exciting concept in health and disease and provides the rationale for the present project. Findings demonstrate that gut microbiota modulates mental capacities such as brain plasticity and cognitive functions in older adults, as well as stress related mental illness. The composition of the intestinal microbiota in older people (>65 years) differs from the core microbiota and diversity levels of younger adults. With age, gut populations of beneficial microbes show a marked decline. As diet has been shown to markedly promote microbiota biodiversity, it is hypothesized that diet-induced changes in microbiota may provide a novel approach for the treatment of mental health. Although insomnia is strongly linked to mental health (e.g., depression and anxiety), as well as cognitive and motor performance, the effects of diet-induced microbiota alterations, based on individual microbiota composition, on late life insomnia is currently unknown. The proposed project will be the first to investigate the associations between gut microbiota and sleep, and assess the potential of a six-months personalized, diet-induced microbiota alterations intervention (PDM), aimed to improve insomnia in older adults. We will also look at cognitive, motor and mental health factors as possible mediators in this relationship. Specifically, we will test the associations between microbiota composition and sleep quality, both cross-sectionally and longitudinally, i.e., following a PDM intervention; evaluate the impact of PDM on changes in cognitive, motor and mental health functions; and identify the mediating roles of changes in cognitive, motor and mental functioning on the effects of a PDM intervention on sleep quality. Findings are expected to improve the quality of life of older adults by enhancing their sleep, functional status, mental health and overall wellbeing.

Official Title
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Two-armed, Single-blind Randomized Clinical Trial for Older Adults With Insomnia

Conditions
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Insomnia

Intervention / Treatment
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* Behavioral: PDM nutritional intervention
* Behavioral: General information on nutrition and health


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Based on DSM-5 criteria of diagnosed chronic insomnia in adults, participants will be included if they report difficulties in initiating or maintaining sleep or early morning awakening at least three nights per week that lasts for a minimum of three months, and impaired daytime functioning. Exclusion Criteria: Based on standard clinical history questionnaires and sleep questionnaires, participants will be excluded if they are less than 65 years, have any significant visual or hearing impairments or chronic pain, if they have or had significant and unstable medical, neurological, or psychiatric illness, if they are alcohol or drug abusers or taking psychiatric medication, or if they had sleep apnea syndrome (SAS) or periodic limb movement disorder during sleep (PLMD).

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PDM nutritional intervention<br> | Behavioral: PDM nutritional intervention<br>* personalized, diet-induced alterations in microbiota (PDM) for six months. (1) A 14-day running-in, no-treatment baseline assessment of all outcomes (T0); (2) A 6-month intervention period, with repeated assessments of all outcomes during the last two weeks of months 3 (T1) and 6 (T2). (3) A 12 month follow up (T3).<br>|
| Experimental: control<br>General information on nutrition and health | Behavioral: General information on nutrition and health<br>* General information on nutrition and health for six months: (1) A 14-day running-in, no-treatment baseline assessment of all outcomes (T0); (2) A 6-month intervention period, with repeated assessments of all outcomes during the last two weeks of months 3 (T1) and 6 (T2). (3) A 12 month follow up (T3),<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ISI - Insomnia sevirity Index | Insomnia Severity Index is based on DSM-4 carteria for insomnia surveys will be completed once at all four study waves (T0-T3) | one year | 
| Actigraphy based Insomnia | Objective sleep measurements: Actigraphy: wrist-worn ambulatory device/ To obtain a composite score for insomnia based on actigraphy, the following cutoff will be used: sleep efficiency<=85%; and sleep onset latency (SOL) and/or wake after sleep onset (WASO) >=30 minutes, at least 3 times per week. Two- week assessments will be repeated during all four study waves (T0-T3) | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insomnia by the consensus sleep diary | To obtain a composite score for insomnia based on the consensus sleep diary, the following cutoff will be used: sleep efficiency<=85%; and sleep onset latency (SOL) and/or wake after sleep onset (WASO) >=30 minutes, at least 3 times per week. Two- week assessments will be repeated during all four study waves (T0-T3) | one year | 
| Insomnia by the The Pittsburgh Sleep Quality Index | The Pittsburgh Sleep Quality Index (PSQI) assesses sleep quality over a 1-month time interval. Its composite global score is the sum of 7 subscore domains of sleep quality. will be completed once at all four study waves (T0-T3) | one year | 
| Cognitive Functioning | Cognitive performance will be evaluated using the computerized Cantab connect research neuropsychological examination for neurocognitive evaluation, which consists of three 20-minute sessions that measure a wide variety of cognitive The Cantab connect research computerized neurocognitive evaluation was specially developed to provide a sensitive test to detect reduction in cognitive functioning among older adults, and it simultaneously provides several measures of cognitive functioning. The software is easy to use and self-explanatory-it guides the user, describes progress rates, and points out areas of difficulty. Assessments will be repeated at all study waves (T0-T3). | one year | 
| Motor Assessment- Gait | Gait will be evaluated as a composite score based on walking speed and stride variability, as a single task, and together with a cognitive task (e.g., subtraction by 3) as a dual task. once at all four study waves (T0-T3) | one year | 
| Motor Assessment- Activity | Daily activity assessment will be based on a composite score of step count and energy expenditure. once at all four study waves (T0-T3) | one year | 
| Wellbeing and Mental health status | Wellbeing will be assessed using the World Health Organization Quality of Life short form questionnaire (WhoQOL-BREF). These assessments will be carried out at all study waves (T0-T3). | one year | 
| Mental health status - Depression | Depression will be assessed using the Geriatric Depression Scale (GDS). These assessments will be carried out at all study waves (T0-T3). | one year | 
| Mental health status - Anxiety | Anxiety will be assessed using the ZUNG selfrating and anxiety scale These assessments will be carried out at all study waves (T0-T3). | one year |