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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Obesity Associated Disorder
• Intervention / Treatment: Drug: Treatment with Akkermansia muciniphila; Other: Treatment with placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Foshan, Guangdong, China, 514500
      • Recruiting
      • The Seventh Affiliated Hospital of Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Aged 18-65
2. Overweight/obesity (24.0≤BMI≤40.0 kg/m^2)
3. Subjects rated as insulin resistant based on homeostasis model (HOMA)
4. 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.
5. 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:

1. 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)；
2. Subjects who need or are using hypoglycemic drugs (including insulin)
3. Subjects who are taking liver medicine
4. Subjects who has had undergone bariatric surgery before
5. Subjects who has Acute or chronic progressive or chronic unstable disease
6. Subjects with Liver and kidney insufficiency, serious cardiovascular and cerebrovascular diseases
7. Subjects with acute diabetic complications such as diabetic ketoacidosis or diabetic hypertonic coma within within latest 3 months
8. History of intestinal or intestinal surgery within 1 year, or non-gastrointestinal surgery within 6 months
9. Excessive alcohol consumption in the last 10 years (more than 30 g/ day for male and 20g/ day for female)
10. Pregnant or lactating subjects
11. Subjects that the investigator considers need to excluded due to other causes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: low-dose Akkermansia muciniphila group; They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks)	Drug: Treatment with Akkermansia muciniphila; 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.
Experimental: high-dose Akkermansia muciniphila group; They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks)	Drug: Treatment with Akkermansia muciniphila; 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.
Placebo Comparator: Placebo group; They were treated with one bag of test drugs (one bag each time, twice a day, for 12 weeks)	Other: Treatment with placebo; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yu Chen

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Anticipated): December 31, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 7, 2022
• First Submitted That Met QC Criteria: February 7, 2023
• First Posted (Actual): February 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 18, 2023
• Last Update Submitted That Met QC Criteria: April 14, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: obesity; insulin resistance; metabolism; Akkermania muciniphila; fecal flora
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Insulin Resistance
• Other Study ID Numbers: ZY19-202201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: In order to protect the privacy and security of the subject, the subject data will not be provided to other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No