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

Phase 2

Active, not recruiting

• Conditions: Type 2 Diabetes; Obese; Overweight
• Interventions: Drug: WST01 strain product; Drug: placebo powder

• Registration Number: NCT04797442
• Lead Sponsor: Shanghai Jiao Tong University School of Medicine

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-03-03
• Study First Submitted QC: 2021-03-11
• Study First Posted: 2021-03-15
• Study Start: 2021-07-15
• Primary Completion: 2022-11-09
• Status Verified: 2023-10
• Last Update Submitted: 2023-10-16
• Last Update Posted: 2023-10-17
• Study Completion: 2024-03-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental	WST01 strain product	-
Placebo comparator	placebo powder	-

Primary Outcome Measures

Name	Time	Method
Fasting plasma glucose levels	12 weeks	change of fasting plasma glucose from baseline
Body weight	12 weeks	change of body weight from baseline

Secondary Outcome Measures

Name	Time	Method
Glycated haemoglobin (HbA1c)	12 weeks
Serum HDL-c	12 weeks
Energy expenditure	12 weeks	using metabolic chamber to measure energy expenditure
Inflammation markers	12 weeks	including hs-CRP, TNF-alfa, IL-6, and IL-8, etc
Systolic and diastolic blood pressure	12 weeks	Safety outcomes
Body temperature	12 weeks	Safety outcomes
Hepatic function	12 weeks	including alanine aminotransferase, aspartate aminotransferase，ɣ-glutamyltransferase, and alkaline phosphatase
Blood metabolomics profile measurement	12 weeks	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.
Pulse rate	12 weeks	Safety outcomes
Red blood cell (RBC) count	12 weeks	Safety outcomes
Fat mass	12 weeks	using DEXA scan to measure fat mass
2-hour post-prandial plasma glucose levels	12 weeks
2-hour post-prandial GLP-1 levels	12 weeks
Serum triglycerides	12 weeks
Renal function	12 weeks	including serum urea nitrogen, serum creatinine, and serum urinary acid
Area of visceral and subcutaneous fat	12 weeks
Adverse events	12 weeks	Safety outcomes
Gut microbiome	12 weeks	including fecal intestinal flora metagenome
Fasting serum insulin levels	12 weeks
Serum LDL-c	12 weeks
2-hour post-prandial serum C peptide levels	12 weeks
Fasting glucagon-like peptide-1 (GLP-1) levels	12 weeks
2-hour post-prandial serum insulin levels	12 weeks
Serum total cholesterol	12 weeks
Waist and hip circumference	12 weeks
White blood cell (WBC) count	12 weeks	Safety outcomes
Hemoglobin levels	12 weeks	Safety outcomes
Platelet count	12 weeks	Safety outcomes
Fasting serum C peptide levels	12 weeks
Lean mass	12 weeks	using DEXA scan to measure lean mass

Trial Locations

Locations (1)

Dep.endocrinology of Shanghai Ruijin Hospital, Shanghai Jiaotong university school of medcine; 🇨🇳 Shanghai, Shanghai, China