A Clinical Study to Evaluate the Effects of Akkermansia Muciniphila on Insulin Resistance Among Obese Subjects.

Study Overview
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Brief Summary
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In this study, the drug Akkermania muciniphila has been proved to play an important role in the occurrence and development of obesity related metabolic diseases. The purpose of this study was to evaluate the safety and efficacy of AKK in the treatment of insulin resistance related obesity. In this study, a single center, randomized, double-blind, placebo-controlled design was adopted. 120 patients with obesity related to insulin resistance were included in this study, and were allocated to live bacteria high-dose group, live bacteria low-dose group, and placebo group at a ratio of 1:1:1. The study lasted for 12 weeks. The changes of body fat, glucose metabolism, lipid metabolism indicators, and fatty liver changes compared with the baseline at the end of the treatment were analyzed. In addition, glucagon like peptide-1 (GLP-1) in plasma and inflammatory markers (hsCRP, TNF) in blood will be analyzed before and after treatment- α、 IL-6、IL-8、IL-1 β） Level, plasma LPS level, oxygen/hydrogen/methane level in methane hydrogen breath test, changes in fecal flora structure, and the mechanism of AKK bacteria affecting insulin resistance by analyzing bacterial metabonomics molecular spectrum in plasma and urine.

Detailed Description
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The purpose of this study was to evaluate the safety and efficacy of AKK in the treatment of insulin resistance related obesity. In this study, a single center, randomized, double-blind, placebo-controlled design was adopted. 120 patients with obesity related to insulin resistance were included in this study, and were allocated to live bacteria high-dose group, live bacteria low-dose group, and placebo group at a ratio of 1:1:1. The study lasted for 12 weeks. The changes of body fat, glucose metabolism, lipid metabolism indicators, and fatty liver changes compared with the baseline at the end of the treatment were analyzed. In addition, glucagon like peptide-1 (GLP-1) in plasma and inflammatory markers (hsCRP, TNF) in blood will be analyzed before and after treatment- α、 IL-6、IL-8、IL-1 β） Level, plasma LPS level, oxygen/hydrogen/methane level in methane hydrogen breath test, changes in fecal flora structure, and the mechanism of AKK bacteria affecting insulin resistance by analyzing bacterial metabonomics molecular spectrum in plasma and urine.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Study to Evaluate the Effects of Akkermansia Muciniphila on Insulin Resistance Among Obese Subjects.

Conditions
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Obesity Associated Disorder

Intervention / Treatment
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* Drug: Treatment with Akkermansia muciniphila
* Other: Treatment with placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 Overweight/obesity (24.0≤BMI≤40.0 kg/m^2) Subjects rated as insulin resistant based on homeostasis model (HOMA) Fertility subjects (including male and female subjects) agreed to take effective contraceptive measures that the investigator accepted during and within 3 months after the trial (e.g. intrauterine device or a condom), the fertility female subjects with serum human chorionic gonadotropin test negative results within 7 days before the investigational product administration. Infertile female must be surgically infertile or at least 1 year after menopause. Subjects should understand the nature, significance, potential benefits, inconvenience and risks of the study before the trial begins, fully understand and voluntarily sign the informed consent. Exclusion Criteria: Subjects with Type 1 diabetes 、Single gene mutation diabet,Diabetes due to pancreatic injury,Iatrogenic obesity (excluding those who have stopped medication for more than 1 year), or other secondary diabetes (such as Cushing's syndrome, thyroid dysfunction, or acromegaly)； Subjects who need or are using hypoglycemic drugs (including insulin) Subjects who are taking liver medicine Subjects who has had undergone bariatric surgery before Subjects who has Acute or chronic progressive or chronic unstable disease Subjects with Liver and kidney insufficiency, serious cardiovascular and cerebrovascular diseases Subjects with acute diabetic complications such as diabetic ketoacidosis or diabetic hypertonic coma within within latest 3 months History of intestinal or intestinal surgery within 1 year, or non-gastrointestinal surgery within 6 months Excessive alcohol consumption in the last 10 years (more than 30 g/ day for male and 20g/ day for female) Pregnant or lactating subjects Subjects that the investigator considers need to excluded due to other causes.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose Akkermansia muciniphila group<br>They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) | Drug: Treatment with Akkermansia muciniphila<br>* 120 subjects were randomly assigned to ZY19 low-dose group, ZY19 high-dose group and placebo group at a ratio of 1:1:1. They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) in ZY19 low-dose group, ZY19 high-dose group and placebo group respectively.<br>|
| Experimental: high-dose Akkermansia muciniphila group<br>They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) | Drug: Treatment with Akkermansia muciniphila<br>* 120 subjects were randomly assigned to ZY19 low-dose group, ZY19 high-dose group and placebo group at a ratio of 1:1:1. They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) in ZY19 low-dose group, ZY19 high-dose group and placebo group respectively.<br>|
| Placebo Comparator: Placebo group<br>They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) | Other: Treatment with placebo<br>* 120 subjects were randomly assigned to ZY19 low-dose group, ZY19 high-dose group and placebo group at a ratio of 1:1:1. They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks) in ZY19 low-dose group, ZY19 high-dose group and placebo group respectively.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weight after 12weeks | Change from baseline in weight | Baseline , Day84 | 
| HOMA-IR after 12weeks | Change from baseline in HOMA-IR | Baseline , Day84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c after 12weeks | Change from baseline in HbA1c | Baseline , Day84 | 
| Fasting and OGTT 2h blood glucose levels after 12weeks | Change from baseline in Fasting and OGTT 2h blood glucose levels | Baseline , Day84 | 
| Fasting and OGTT 2h insulin and C-peptide levels after 12weeks | Change from baseline in Fasting and OGTT 2h insulin and C-peptide levels | Baseline , Day84 | 
| BMI, waist circumference, waist-to-hip ratio after 12weeks | Change from baseline in BMI, waist circumference, waist-to-hip ratio | Baseline , Day84 | 
| Total body fat and visceral adipose tissue after 12weeks | Change from baseline in Total body fat and visceral adipose tissue | Baseline , Day84 | 
| Blood lipid profile after 12weeks | Change from baseline in Blood lipid profile(include Triglycerides, total cholesterol, LDL-c, HDL-c) | Baseline , Day84 | 
| Liver enzyme after 12weeks | Change from baseline in Liver enzyme(include AST、ALT、GGT) | Baseline , Day84 | 
| Fibroscan CAP after 12weeks | Change from baseline in Fibroscan CAP | Baseline , Day84 | 
| Incidence and severity of TEAE and SAE | Clinical significant Vital signs, physical and laboratory results | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Akkermania muciniphila, obesity, insulin resistance, metabolism, fecal flora