Clinical trial NCT04797442: Effect of Akkermansia Muciniphila WST01 Strain in Overweight or Obese Patients With Type 2 Diabetes
Official title: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Clinical Trial to Evaluate the Effect of Akkermansia Muciniphila WST01 Strain in Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Obese
Overweight
Type 2 Diabetes
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2021-03-15
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Body weight
timeFrame: 12 weeks
measure: Fasting plasma glucose levels
timeFrame: 12 weeks
Secondary outcomes:
measure: Gut microbiome
timeFrame: 12 weeks
measure: Glycated haemoglobin (HbA1c)
timeFrame: 12 weeks
measure: 2-hour post-prandial plasma glucose levels
timeFrame: 12 weeks
measure: Fasting serum insulin levels
timeFrame: 12 weeks
measure: 2-hour post-prandial serum insulin levels
timeFrame: 12 weeks
measure: Fasting glucagon-like peptide-1 (GLP-1) levels
timeFrame: 12 weeks
measure: 2-hour post-prandial GLP-1 levels
timeFrame: 12 weeks
measure: Serum triglycerides
timeFrame: 12 weeks
measure: Serum total cholesterol
timeFrame: 12 weeks
measure: Serum LDL-c
timeFrame: 12 weeks
measure: Serum HDL-c
timeFrame: 12 weeks
measure: Area of visceral and subcutaneous fat
timeFrame: 12 weeks
measure: Waist and hip circumference
timeFrame: 12 weeks
measure: Energy expenditure
timeFrame: 12 weeks
measure: Blood metabolomics profile measurement
timeFrame: 12 weeks
measure: Inflammation markers
timeFrame: 12 weeks
measure: Systolic and diastolic blood pressure
timeFrame: 12 weeks
measure: Body temperature
timeFrame: 12 weeks
measure: Pulse rate
timeFrame: 12 weeks
measure: White blood cell (WBC) count
timeFrame: 12 weeks
measure: Red blood cell (RBC) count
timeFrame: 12 weeks
measure: Hemoglobin levels
timeFrame: 12 weeks
measure: Platelet count
timeFrame: 12 weeks
measure: Hepatic function
timeFrame: 12 weeks
measure: Renal function
timeFrame: 12 weeks
measure: Adverse events
timeFrame: 12 weeks
measure: Fasting serum C peptide levels
timeFrame: 12 weeks
measure: 2-hour post-prandial serum C peptide levels
timeFrame: 12 weeks
measure: Lean mass
timeFrame: 12 weeks
measure: Fat mass
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Dep.endocrinology of Shanghai Ruijin Hospital, Shanghai Jiaotong university school of medcine
state: Shanghai
Study officials:
References: