Impact of Different Types of Higher Dietary Protein Intake on Sleep Quality in Singapore Older Adults

Study Overview
=================
Brief Summary
-----------------
Today, insufficient sleep has become a growing global problem. Sleep is essential to health and changes in sleep patterns are a part of the aging process. Inadequate and low-quality sleep also increases the risk for age-related cognitive decline and disease conditions. More importantly, due to COVID-19 health emergency, there is a significant increase of psychological distress and symptoms of mental illness and a worsening of quality of sleep. Therefore, there is an urgent need to investigate the way of improving sleep quality, in particular during and post COVID-19 period, in older adults. One of the possible strategies in improving sleep quality with lifestyle modification is having higher-protein diet. However, this effect has not been fully elucidated in older adults. In addition, the effect of type of dietary protein on sleep quality is inconclusive and there is no clinical trial which assessed the differential response in sleep quality between animal-sourced protein vs. plant-sourced protein. Therefore, the purpose of this research project is to assess the impact of different types of higher dietary protein intake on sleep quality in Singapore older adults. Findings from the proposed research will provide the scientific evidence of the beneficial effects of regularly consuming higher-protein diet on sleep quality in Singapore older adults. In addition, this research may validate the differential effect of different type of dietary protein on sleep quality. The results from the proposed research will also assist a practical guidance of nutritional behaviour changes providing sleep promoting effects to a large proportion of the Singapore population.

Detailed Description
-----------------
During the 16-week intervention, subjects will be randomly assigned to 1 of 3 groups including consuming normal-protein diet, higher-protein diet supplemented with micellar casein protein or higher-protein diet supplemented with soy protein. Recommended Dietary Allowances for healthy Singaporean. Normal-protein diet will be designed following a healthy eating pattern diet, referred to as the My Healthy Plate launched by Health Promotion Board and subjects will consume 3 servings of dietary protein. Higher-protein diet will also follow a healthy eating pattern diet while subjects will additionally take either 20 g micellar casein protein isolate or 20 g soy protein isolate. One-on-one dietary counselling and written instructions for each subject will be provided by a research dietitian and trained research staff. Compliance with the diet interventions will be promoted by frequent online and in-person contact and dietary assessment. Blood amino acid concentration will also be assessed as an indicator of compliance to the protein intake.

Official Title
-----------------
Impact of Different Types of Higher Dietary Protein Intake on Sleep Quality in Singapore Older Adults

Conditions
-----------------
Sleep, Gut Microbiome, Cardiometabolic Risk

Intervention / Treatment
-----------------
* Other: Dietary protein


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults 60-85 years old Not following HPB diet Exclusion Criteria: Weight change > 3kg in the past 3 months Exercise vigorously over the past 3 months Drinking more than 2 alcoholic drinks per day (if applicable) Pre-menopausal women Taking dietary supplements or medications which may impact sleep outcomes (e.g. Nutritional Shakes (e.g. Ensure), Trp, 5-HTP or melatonin supplementations) the past 1 month Taking dietary supplements which may impact the gut microbiota (e.g. antibiotics, prebiotics, probiotics) the past 2 months (a list of fermented foods) Impaired renal function (normal values: estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 calculated by chronic kidney disease epidemiology collaboration equation; CKD EPI) Soy intolerance and/or allergy or any medical conditions that may be affected by consumption of soy products (e.g. gout) Prescribed and taking antihypertensive/cholesterol-lowering/ type-2 diabetic medication or Chinese medicine herb which started less than 3 years prior to the intervention participation Diagnosed with gut/gastrointestinal issues such as lactose intolerance and irritable bowel syndrome (IBS)

Ages Eligible for Study
-----------------
Minimum Age: 60 Years
Maximum Age: 85 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a 16-week factorial study design with subjects randomly assigned to consume normal-protein diet, higher-protein diet with micellar casein protein isolates or higher-protein diet with soy protein isolates. Subjects' sleep quality will also be evaluated and screened using the PSQI questionnaire (GSS ≤5 [good sleepers] vs. GSS >5 [poor sleepers]). Sixty-eight older men and women (aged 60-85y, approximately half men and half women) will be recruited with the expectation that ≥ 54 subjects (≥ 18 subjects per group) will complete the study (≤ 20% dropout rate). The 18 subjects recruited for each of the intervention group were further classified into poor (n=9) and good sleepers (n=9).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Normal protein diet (control)<br>Subjects are to consume normal-protein diet based on the My Healthy Plate diet (launched by Health Promotion Board of Singapore) for the duration of the 16-week study. | |
| Experimental: High protein diet (soy)<br>Subjects are to consume higher-protein diet by following the My Healthy Plate diet (launched by Health Promotion Board of Singapore) and 20g of soy protein isolate for the duration of the 16-week study. | Other: Dietary protein<br>* Intervention of the study include consuming a higher protein diet. Depending on the group allocation, this is done by asking the subjects to follow My Healthy Plate diet and consumption of 20g of protein isolates (casein or soy).<br>|
| Experimental: High protein diet (Micellar Casein)<br>Subjects are to consume higher-protein diet by following the My Healthy Plate diet (launched by Health Promotion Board of Singapore) and 20g of micellar casein isolate for the duration of the 16-week study. | Other: Dietary protein<br>* Intervention of the study include consuming a higher protein diet. Depending on the group allocation, this is done by asking the subjects to follow My Healthy Plate diet and consumption of 20g of protein isolates (casein or soy).<br>|

What is the study measuring?
-----------------
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, week 12 and week 16) | 
| 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, week 12 and week 16) | 
| Change in blood amino acid concentration | Amino acid concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in blood serotonin concentration | Serotonin concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in urinary 6-sulfatoxymelatonin (aMT6s) concentration | 6-sulfatoxymelatonin (aMT6s) concentration in the urine samples will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in fecal microbiome composition | High-throughput sequencing method (using Illumina MiSeq platforms) will be used to assess the changes in gut microbiome composition | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in fecal short chain fatty acid (SCFA) concentration | SCFA concentration in fecal samples will be measured. | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in serum lipopolysaccharide binding protein (LBP) concentration | LBP concentration in blood samples will be measured. | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in blood short chain fatty acid (SCFA) concentration | SCFA concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in fecal bile acids | Bile acids concentration will be determined from fecal samples of the subjects | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in fecal zonulin | Zonulin concentration will be determined from fecal samples of the subjects | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in fecal calprotectin | Calprotectin concentration will be determined from fecal samples of the subjects | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in urinary creatinine concentration | Creatinine concentration in the urine samples will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Estimated Glomerular Filtration Rate (eGFR) | The estimated Glomerular Filtration Rate (eGFR) of the subjects will be measured from the blood | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Trimethylamine N-oxide (TMAO) | Trimethylamine N-oxide (TMAO) concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Glucose | Glucose concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Triglyceride | Triglyceride concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Cholesterol | Total cholesterol concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Low-density Lipoprotein-cholesterol (LDL) | LDL concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood High-density Lipoprotein-cholesterol (LDL) | HDL concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Advanced Glycation End-product (AGEs) | AGEs concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Skin Advanced Glycation End-product (AGEs) | Using a scanner, the AGEs levels in the skin will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Blood Interleukin-6 (IL-6) | Interleukin-6 (IL-6) concentration in the blood will be measured | Every 8 weeks (week 0 , week 8 and week 16) | 
| Change in Endothelial Function | Endothelial functions are determined by the function of endothelial progenitor cells | Baseline and Post-intervention (week 0 and week 16) | 
| Change in Flow Mediate Dilation | Flow mediate dilation (%) | Baseline and Post-intervention (week 0 and week 16) | 
| 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, week 12 and week 16) | 
| Change in waist circumference | Waist circumference (in cm) will be measured | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 
| Change in blood pressure | Systolic and diastolic blood pressure (in mmHg) will be measured by a blood pressure monitor. | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 
| Dietary assessment | Dietary assessment will be assessed by 3-day dietary food record | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 
| Change in mood (stress) | Perceived Stress Scale (PSS) will be used to assess the stress levels | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 
| Change in mood (depression) | Geriatric Depression Scale (GDS) Assessment will be used to assess the depression status | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 
| Change in mood (anxiety) | Geriatric Anxiety Inventory (GAI) Assessment will be used to assess the anxiety status. | Every 4 weeks (week 0, week 4, week 8, week 12 and week 16) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dietary protein