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

Obesity Associated Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05720299
• Other study ID #: ZY19-202201
• Status: Recruiting
• Phase: N/A
• Start date: March 29, 2023
• Est. completion date: December 31, 2024

Study information

• Verified date: April 2023
• Source: The Seventh Affiliated Hospital, Southern Medical University
• Contact: Yu Chen, Doctor
• Phone: +86-13824482875
• Email: askasky[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 31, 2024
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Insulin Resistance
• Obesity Associated Disorder

Intervention

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.

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.

Locations

Country	Name	City	State
China	The Seventh Affiliated Hospital of Southern Medical University	Foshan	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Yu Chen

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight after 12weeks	Change from baseline in weight	Baseline , Day84
Primary	HOMA-IR after 12weeks	Change from baseline in HOMA-IR	Baseline , Day84
Secondary	HbA1c after 12weeks	Change from baseline in HbA1c	Baseline , Day84
Secondary	Fasting and OGTT 2h blood glucose levels after 12weeks	Change from baseline in Fasting and OGTT 2h blood glucose levels	Baseline , Day84
Secondary	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
Secondary	BMI, waist circumference, waist-to-hip ratio after 12weeks	Change from baseline in BMI, waist circumference, waist-to-hip ratio	Baseline , Day84
Secondary	Total body fat and visceral adipose tissue after 12weeks	Change from baseline in Total body fat and visceral adipose tissue	Baseline , Day84
Secondary	Blood lipid profile after 12weeks	Change from baseline in Blood lipid profile(include Triglycerides, total cholesterol, LDL-c, HDL-c)	Baseline , Day84
Secondary	Liver enzyme after 12weeks	Change from baseline in Liver enzyme(include AST?ALT?GGT)	Baseline , Day84
Secondary	Fibroscan CAP after 12weeks	Change from baseline in Fibroscan CAP	Baseline , Day84
Secondary	Incidence and severity of TEAE and SAE	Clinical significant Vital signs, physical and laboratory results	Up to 12 weeks