Evaluation the Effect of AKK Formula on Intestinal Microbiota Regulation and Body Composition

Study Overview
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Brief Summary
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The AKK formula, a prebiotic blend, can effectively promote the proliferation of A. muciniphila. In this study, we attempt to explore the clinical efficacy of AKK formula for A. muciniphila proliferation and weight management.

Detailed Description
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This is a double-blind, randomized, parallel and placebo-controlled study. Subjects are informed to consume the samples daily for 8 weeks. The person who is evaluated as obesity by the investigator will be invited to participate in this trial. In this study, we attempt to explore the clinical efficacy of AKK formula for A. muciniphila proliferation and weight management.

Official Title
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Evaluation the Effect of AKK Formula on Intestinal Microbiota Regulation and Body Composition

Conditions
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Body Weight Changes, Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: AKK formula prebiotic sachet
* Dietary Supplement: Placebo sachet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects shall have a body mass index (BMI) of >23.0 to <32.5.0 kg/m2. Subjects shall have waist circumference of >80 cm for men and women. Subject is willing to maintain habitual dietary, lifestyle, and physical activity throughout the trial and do not plan to change the place of living during the study. Subject understands the study procedures and signs forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the Study Investigator. Exclusion Criteria: Clinically important gastrointestinal condition that would potentially interfere with the evaluation of study products (e.g., inflammatory bowel disease, irritable bowel syndrome, gastric reflux, indigestion, dyspepsia, Crohn's disease, celiac disease, history of gastrointestinal surgical intervention for inducing weight loss, gastroparesis, and clinically significant lactose or gluten intolerance or other food/food component allergies). Recent (within 2 weeks of Visit 1, Day -7 - screening visit) history of an episode of acute GI illness such as nausea/vomiting or diarrhea (defined as >3 loose or liquid stools/d). Self-reported history (within 6 weeks of Visit 1, Day -7 -screening visit) of constipation (< 3 bowel movements/week) or diarrhea (loose stools >3 loose or liquid stools in one day) that in the judgement of the Study Investigator is not due to acute infection (e.g., stomach flu), food poisoning, temporary medication, etc. Subjests with mental disorder(depression, schizophrenia), cardiovascular disease/Arrhythmia/Heart Failure/Myocardial Infarction/or other Heart Condition, Hypothyroidism Or Uncontrolled Diabetic Gastrointestinal Disease (Crohn's Disease)/Gastrointestinal Resection Surgery/Irritable Bowel Syndrome, kidney condition, autoimmune disorder, Thyroid or hormonal abnormalities/Abnormalities If the immune system that can affect the weight of thyroid levels, like anemia/porphyrinosis, pancreatitis etc . Uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) as defined by blood pressure measured on Visit 1. Stable use of hypertension medication is allowed (defined as no change in medication regimen within the 3 mo prior to Visit 1.) Any known food allergy, intolerance, or sensitivity to study product ingredients. Extreme dietary habits, eating disorders or physical activity patterns at the discretion of the Study Investigator. History or presence of cancer in the prior 2 years, except for non-melanoma skin cancer. Major trauma or any other surgical event within 3 months of Visit 1. Signs or symptoms of an active infection of clinical relevance within 5 days of Visit 1. Weight loss or gain >4.5 kg in the 3 months prior to Visit 1. Current use or planned use/participation in any weight loss regimen during the study period. Anti-biotic, antifungal, or antiparasitic use within 3 months of Visit 1 and throughout the study period. Use of anti-obesity, blood sugar lowering medications, insulin injections, hormones, diuretics , hormoneal treatment orsteroids within 1 month of Visit 1 and throughout the study period. Use of nasal and non-prescription topical treatments is permitted. Chronic use (i.e., daily or on a regular basis) of anti-inflammatory medications (e.g., NSAIDS) within 1 month of Visit 1. Use of medications (over-the-counter or prescription) and/or dietary supplements known to influence GI function including, but not limited to prebiotics, probiotics laxatives and/or enemas - including suppositories, fiber supplements, H2 blockers, proton pump inhibitors, antacids, anti-diarrheal agents, antidepressants, and/or anti-spasmodics within 3 weeks of Visit 1. Standard multi-vitamin/multi-mineral supplements are permitted. Subject has undergone endoscopy or endoscopy preparation within 3 months prior to Visit 1. Exposure to any non-registered drug product, including street drugs, within 4 weeks prior to Visit 1. Recent history (within 12 months of Visit 1) of alcohol or substance abuse. Alcohol abuse is defined as >14 drinks/week (1 drink = 12 oz (354 ml) beer, 5 oz (148 ml), or 1 ½ oz (44 ml) distilled spirits). Subject has a condition that, in the opinion of the Study Investigator, would interfere with his/her ability to provide informed consent, comply with the study protocol, confound interpretation of study results, or place the subject at undue risk. Female subjects who typically experience changes in GI symptoms or bowel habits (e.g., increased or decreased laxation, bloating, abdominal cramping) at the time of menstruation. Female subjects with irregular menstruation which does not allow for easy scheduling of stool collection outside of the menstrual period. Female subject who is pregnant, planning to be pregnant during the study period, lactating, or is of childbearing potential and is unwilling to commit to the use of a medically approved form of contraception throughout the study period. Subjects who become pregnant during the study will be dismissed from the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo sachet<br>consume 1 sachet per day for 8 weeks | Dietary Supplement: Placebo sachet<br>* 5 g/sachet, containing Indigestible Maltodextrin, Crystalline Maltitol, Calcium Carbonate, Citric Acid, Steviol Glycosides, and flavor. Subjects will consume 1 sachet per day for 8 weeks.<br>|
| Experimental: AKK formula sachet<br>consume 1 sachet per day for 8 weeks | Dietary Supplement: AKK formula prebiotic sachet<br>* 5 g/sachet, containing AKK formula, Indigestible Maltodextrin, Crystalline Maltitol, Calcium Carbonate, Citric Acid, Steviol Glycosides, and flavor. Subjects will consume 1 sachet per day for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relative abundance of Akkermansia muciniphila in gut | Collect subject's feces for bacterial analysis. Akkermansia muciniphila will be quantified by quantitative PCR. | Change from Baseline relative abundance of A. muciniphila at 8 weeks | 
| The change of waist circumference | The waist circumference will be assessed by measuring tape. Unit: centimeter | Change from Baseline waist circumference at 4 weeks, and 8 weeks | 
| The change of Waist-to-height ratio | Waist-to-height ratio can be obtained by dividing waist size by height and is an effective indicator of risks associated with obesity. | Change from Baseline Waist-to-height at 4 weeks, and 8 weeks | 
| The change of body mass index (BMI) | BMI is a measurement of a person's leanness or corpulence based on their height and weight, and is intended to quantify tissue mass.The body mass index (BMI, kg/m^2) and body mass (kg) will be assessed by InBody. | Change from Baseline BMI at 4 weeks, and 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change of total body mass | The total body mass (kg) will be assessed by Bioelectrical impedance analysis (BIA). | Change from Baseline total body mass at 4 weeks, and 8 weeks | 
| The change of total lean mass | The total lean mass (kg) will be assessed by Bioelectrical impedance analysis (BIA). | Change from Baseline total lean mass at 4 weeks, and 8 weeks | 
| The change of total fat mass | The total fat mass (kg) will be assessed by Bioelectrical impedance analysis (BIA). | Change from Baseline total fat mass at 4 weeks, and 8 weeks | 
| The change of total fat rate | The total fat rate (%) will be assessed by Bioelectrical impedance analysis (BIA). | Change from Baseline total fat rate at 4 weeks, and 8 weeks | 
| The change of visceral fat volume | The visceral fat volume (cm^2) will be assessed by Bioelectrical impedance analysis (BIA). | Change from Baseline visceral fat volume at 4 weeks, and 8 weeks | 
| The change of hip circumference | The hip circumference will be assessed by measuring tape. Unit: centimeter | Change from Baseline hip circumference at 4 weeks, and 8 weeks | 
| The change of insulin sensitivity | Insulin sensitivity is assessed by HOMA-IR. HOMA-IR= fasting insulin (microU/L) x fasting glucose (nmol/L)/22.5. Venous blood will be sampled to measure concentrations of fasting glycemia and insulin. | Change from Baseline insulin sensitivity at 8 weeks | 
| The change of total cholesterol | Venous blood will be sampled to measure concentrations of total cholesterol. | Change from Baseline total cholesterol at 8 weeks | 
| The change of High Density Lipoprotein Cholesterol (HDL-C) | Venous blood will be sampled to measure concentrations of HDL-C. | Change from Baseline HDL-C at 8 weeks | 
| The change of Low Density Lipoprotein Cholesterol (LDL-C) | Venous blood will be sampled to measure concentrations of LDL-C. | Change from Baseline LDL-C at 8 weeks | 
| The change of triglyceride | Venous blood will be sampled to measure concentrations of triglyceride. | Change from Baseline triglyceride at 8 weeks | 
| The change of intestinal microbiota | Collect subject's feces for bacterial analysis. Intestinal microbiota will be assessed by Next Generation Sequencing (NGS). | Change from Baseline intestinal microbiota at 8 weeks | 
| The change of gastrointestinal tolerability | Gastointestinal tolerability will be assessed by The Gastrointestinal Symptom Rating Scale (GSRS).The GSRS has a seven-point graded Likert-type scale where 1 represents absence of troublesome symptoms and 7 represents very troublesome symptoms. | Change from Baseline gastrointestinal tolerability at 4 weeks, and 8 weeks | 
| The change of stool type | The stool type will be assessed by The Bristol Stool Form Scale (BSFS) daily. The BSFS is a scale that classifies stools, ranging from the hardest (type 1) to the softest (type 7). | Change from Baseline gastrointestinal tolerability at 4 weeks, and 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Akkermansia muciniphila