Effect of Akkermansia Muciniphila WST01 Strain in Overweight or Obese Patients With Type 2 Diabetes

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Effect of Akkermansia Muciniphila WST01 Strain in Patients With Type 2 Diabetes

The purpose of this study is to conduct a randomized, double-blinded, placebo-controlled, multicenter clinical trial, evaluating the glucose-lowering and weight-loss effects of Akkermansia muciniphila WST01 strain in overweight or obese patients with Type 2 Diabetes.

Study Overview

• Status: Active, not recruiting
• Conditions: Overweight; Type 2 Diabetes; Obese
• Intervention / Treatment: Drug: WST01 strain product; Drug: placebo powder

Detailed Description

In the present study, about 60 overweight/obese and drug naïve type 2 diabetes patients will be enrolled from multiple centers in China. After screening, eligible subjects will be randomized (1:1) into two groups, taking either Akkermansia muciniphila WST01 strain product or placebo product for 12 weeks.

Blood, feces and urine samples will be collected before and after treatment. Metabolic parameters including waist and hip circumference, area of visceral and subcutaneous fat, glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), insulin, glucagon-like peptide 1 (GLP-1), inflammation factors and lipid levels will be measured. Furthermore, the change of gut microbiota and metabolites will be evaluated too.

The primary objective is to determine whether Akkermansia muciniphila WST01 strain has a positive effect in patients with Type 2 Diabetes. The secondary objective is to explore the effect of Akkermansia muciniphila WST01 strain on safety, intestinal flora, insulin sensitivity, and other metabolic indicators and metabolites in the patients.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Dep.endocrinology of Shanghai Ruijin Hospital, Shanghai Jiaotong university school of medcine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Main Inclusion Criteria:

1. Subjects with type 2 diabetes mellitus;
2. Age 18-60 years;
3. Overweight / obesity (24.0 ≤ BMI ≤ 40.0 kg/m2)；
4. Subjects with or without other obesity related metabolic complications (hypertension, dyslipidemia, hyperuricemia, etc.);
5. Subjects with screening HbA1c ≥ 7.0% and ≤ 10.0%, and the fasting blood glucose ≥ 7.0 mmol/l and ≤ 13.3 mmol/l；
6. Subjects who are not taking any medications to control blood glucose;
7. Subjects control blood glucose only by lifestyle intervention (diet and exercise) for at least 2 months before the screening period;
8. Subjects understand the nature, significance, potential benefits, inconvenience, and risks of the study before it starts；
9. Subjects fully understand the study produces and voluntarily sign the informed consent form.

Main Exclusion Criteria:

1. Subjects with a history of taking hypoglycemic drugs;
2. Subjects who are pregnant or in lactation;
3. Subjects with type 1 diabetes, single gene mutation diabetes, diabetes due to pancreatic injury or other secondary diabetes (such as Cushing's syndrome, thyroid dysfunction or acromegaly, etc.);
4. Subjects who were or are using oral hypoglycemic agents or insulin or incretin to control diabetes;
5. Subjects with liver and kidney dysfunction (alanine transaminase(ALT) / aspartate aminotransferase(AST)≥2.5×the upper limit of normal(ULN) set by the hospital, serum creatinine>1×ULN set by the hospital, or eGFR<60mL/min/1.73m2);
6. Surgery with serious cardiovascular and cerebrovascular diseases (such as heart failure, myocardial infarction, cerebral infarction, acute myocarditis, severe arrhythmia, patients receiving interventional therapy, etc.) or stage III hypertension (systolic blood pressure cannot be controlled below 160 mmHg with three antihypertensive drugs);
7. Subjects with acute diabetic complications such as diabetic ketoacidosis or diabetic hyperosmolar coma in the past 3 months;
8. Subjects with a medical history of malignant tumor (except local skin basal cell carcinoma) in the past 5 years;
9. Subjects with a medical history of intestine, or other digestive tract surgery (such as cholecystectomy) within one year, or other non-gastrointestinal surgery within 6 months;
10. Any condition that in the judgement of the investigator precludes participation.

Details please see the study protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental	Drug: WST01 strain product; orally given WST01 strain product, added onto lifestyle. The specific ingredients are the optimized Akkermansia muciniphila WST01 strain powder with maximum live bacteria of 5*10^10 CFU/g (1 g/pack, 3 packs QD, 20-30 min after breakfast)
Placebo Comparator: Placebo comparator	Drug: placebo powder; orally given placebo powder (the specific ingrdients are the excipients of the WST01 strain powder), added onto lifestyle. (3 packs of placebo powder QD, 20-30 min after breakfast)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body weight	change of body weight from baseline	12 weeks
Fasting plasma glucose levels	change of fasting plasma glucose from baseline	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome	including fecal intestinal flora metagenome	12 weeks
Glycated haemoglobin (HbA1c)		12 weeks
2-hour post-prandial plasma glucose levels		12 weeks
Fasting serum insulin levels		12 weeks
2-hour post-prandial serum insulin levels		12 weeks
Fasting glucagon-like peptide-1 (GLP-1) levels		12 weeks
2-hour post-prandial GLP-1 levels		12 weeks
Serum triglycerides		12 weeks
Serum total cholesterol		12 weeks
Serum LDL-c		12 weeks
Serum HDL-c		12 weeks
Area of visceral and subcutaneous fat		12 weeks
Waist and hip circumference		12 weeks
Energy expenditure	using metabolic chamber to measure energy expenditure	12 weeks
Blood metabolomics profile measurement	In aid of LC/MS and GC/MS technique, etc, we will measure the metabolomics molecular profile in blood samples before and after treatment. The metabolomics measurement will help to detect the profile of all kinds of bile acid species, lipids species and amino acid species, etc. The composition change of all these biological molecular induced by the treatment is our major interest rather than single molecular quantification.	12 weeks
Inflammation markers	including hs-CRP, TNF-alfa, IL-6, and IL-8, etc	12 weeks
Systolic and diastolic blood pressure	Safety outcomes	12 weeks
Body temperature	Safety outcomes	12 weeks
Pulse rate	Safety outcomes	12 weeks
White blood cell (WBC) count	Safety outcomes	12 weeks
Red blood cell (RBC) count	Safety outcomes	12 weeks
Hemoglobin levels	Safety outcomes	12 weeks
Platelet count	Safety outcomes	12 weeks
Hepatic function	including alanine aminotransferase, aspartate aminotransferase，ɣ-glutamyltransferase, and alkaline phosphatase	12 weeks
Renal function	including serum urea nitrogen, serum creatinine, and serum urinary acid	12 weeks
Adverse events	Safety outcomes	12 weeks
Fasting serum C peptide levels		12 weeks
2-hour post-prandial serum C peptide levels		12 weeks
Lean mass	using DEXA scan to measure lean mass	12 weeks
Fat mass	using DEXA scan to measure fat mass	12 weeks

Collaborators and Investigators

• Sponsor: Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2021
• Primary Completion (Actual): November 9, 2022
• Study Completion (Estimated): March 31, 2024

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): October 17, 2023
• Last Update Submitted That Met QC Criteria: October 16, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
• Other Study ID Numbers: WST001

Drug and device information, study documents

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