Impact of Nutritional Supplementation on Sleep Quality and Gut Microbiome Composition in Older Adults

Study Overview
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Brief Summary
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The aim of this study is to assess the impact of 5-hydroxytryptophan (5-HTP) supplementation on sleep quality and gut microbiome composition in older adults with normal cognition vs. mild cognitive impairment (MCI) using a randomized controlled trial.

Detailed Description
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This is a 12-wk parallel, single-bind (investigator), prospective study design with subjects randomly assigned to consume 100 mg of 5-HTP or does not consume 5-HTP. Fifty older men and women (aged 60-85y, approximately half men and half women, approximately half subjects with MCI) will be recruited with the expectation that ≥ 40 subjects (≥ 10 subjects per group) will complete the study. Body size, blood pressure, urinary melatonin, sleep quality, cognitive function and mood (including depression and anxiety), gut microbiome, and short chain fatty acids will be assessed. Blood amino acid concentration will be measured as an indicator of compliance to the 5-HTP consumption from the collected blood samples. Relevance to Singapore: The results from the proposed research will assist a practical guidance of nutritional behavior changes providing gut and brain health promoting effects to Singapore older individuals with or without MCI and may result in reducing cost and manpower for cognitive decline care.

Official Title
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Impact of Nutritional Supplementation on Gut-brain Axis in Older Adults With Normal Cognition vs. Mild Cognitive Impairment

Conditions
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Sleep, Gut Microbiome

Intervention / Treatment
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* Dietary Supplement: 5-HTP
* Other: Without 5-HTP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to give an informed consent Age 60 ≤years ≤ 85 years old Weight change < 3kg in the past 3 months Not exercising vigorously over the past 3 months Not taking protein (e.g. Whey isolate, Ensure), tryptophan, serotonin and/or 5-HTP supplements for the past one month Not taking sleep medication and/or dietary supplements for sleep (e.g. melatonin, GABA) for the past one month Not taking prebiotic, probiotic and/or dietary fiber supplementations for the past one month Not taking cognitive/brain supplementations (e.g. gingko biloba, acetylcholine) for the past one month Not taking prescription anti-depressant or pain medication (e.g. Zoloft, Tramadol etc.) No acute illness If taking antihypertensive/cholesterol-lowering/ type 2 diabetic medication, he/she has been taking the medication for more than 5 years prior to the study participation Not smoking Not drinking more than 2 alcoholic drinks per day Exclusion Criteria: Unable to give an informed consent Age < 60 years and >85 years old Weight change >3kg in the past 3 months Exercises vigorously over the past 3 months Taking protein (e.g. Whey isolate, Ensure), tryptophan, serotonin and/or 5-HTP supplements for the past one month Taking sleep medication and/or dietary supplements for sleep (e.g. melatonin, GABA) for the past one month Taking prebiotic, probiotic and/or dietary fiber supplementations for the past one month Taking cognitive/brain supplementation (e.g. gingko biloba, acetylcholine) for the past one month Taking prescription anti-depressant or pain medication (e.g. Zoloft, Tramadol etc.) Having acute illness If taking antihypertensive/cholesterol-lowering/ type 2 diabetic medication, he/she has NOT been taking the medication for less than 5 years prior to the study participation Smoking Drinking more than 2 alcoholic drinks/day

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 85 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Normal subject without 5-HTP<br>Subjects with normal cognition will be randomly assigned to not consuming 5-HTP. | Other: Without 5-HTP<br>* Subject will not take 5-HTP<br>|
| Experimental: Normal subject with 5-HTP<br>Subjects with normal cognition will be randomly assigned to consuming 100 mg of 5-HTP. | Dietary Supplement: 5-HTP<br>* 5-HTP that have Good Manufacturing Practice certification will be used and participants will be suggested to be take the 5-HTP supplementation at bedtime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sleep quality assessed by validated sleep questionnaires | Pittsburgh Sleep Quality Index Questionnaire (PSQI) will be used to assess the sleep quality. Overall score ranging from 0 to 21 points, where lower scores denote a healthier sleep quality. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in sleep quality assessed by electronic equipment | An electronic equipment, actigraphy, will be used to assess the sleep quality, including sleep timing and wake up timing. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in fecal short chain fatty acid (SCFA) concentration as assessed by micromoles per gram (μmol/g) | Fecal SCFA concentration will be measured using gas chromatograph (GC) and assessed by μmol/g. There is no recognized range. Normally the higher level is better. | Pre- and post-intervention (week 0 and week 12) | 
| Change in fecal microbiome composition | High-throughput sequencing method (using Illumina MiSeq platforms) will be used to assess the changes in gut microbiome composition. | Pre- and post-intervention (week 0 and week 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quality of Life: WHOQOL | The World Health Organization Quality of Life Assessment (WHOQOL) will be used to assess the quality of life. Score ranging from 0 to 100 points, where higher scores denote higher quality of life. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in Cognitive function | Montreal Cognitive Assessment (MOCA) will be used to assess the cognitive function. Score ranging from 0 to 30 points. A final total score of 26 and above is considered normal. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in mood (depression) | Geriatric Depression Scale (GDS) Assessment will be used to assess the depression situation. Score ranging from 0 to 15 points. Although differing sensitivities and specificities have been obtained across studies, for clinical purposes a score > 5 points is suggestive of depression and should warrant a follow-up interview. Scores > 10 are almost always depression. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in mood (anxiety) | Geriatric Anxiety Inventory (GAI) Assessment will be used to assess the anxiety situation. Score ranging from 0 to 20 points, where higher scores denote higher level of anxiety. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in urinary melatonin levels as assessed by nanogram per milliliter (ng/mL) | Change in urinary melatonin levels will be assessed by using enzyme linked immunosorbent assay (ELISA) kits. There is no recognized range. Normally the higher level is better. | Pre- and post-intervention (week 0 and week 12) | 
| Change in blood amino acids assessed by nanomole per milliliter (ng/mL) | Amino Acid Analysis System will be used to assess the blood amino acid levels. There is no recognized range. | Pre- and post-intervention (week 0 and week 12) | 
| Change in weight and height | Weight (in kilograms) and height (in meters) will be combined to report BMI in kg/m^2. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Change in waist circumference as assessed by centimeter (cm) | Recommended cutoffs for increased health risk are a waist circumference >102 cm for men and >88 cm for women. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Dietary assessment | Dietary assessment will be assessed by 3-day dietary food record. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 
| Blood pressure as assessed by millimeter of mercury (mmHg) | Systolic and diastolic blood pressure will be measured by a blood pressure monitor. For a normal reading, systolic pressure is between 90 and 120 and diastolic pressure is between 60 and 80. | Every 4 weeks (week 0, week 4, week 8 and week 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nutritional supplementation, Sleep quality, Cognitive function, Gut microbiome