Clinical trial NCT04525300: Gut Microbiome Changes Following Liraglutide Treatment in Obese Subjects or Overweight Subjects With Co-morbidities
Official title: Changes of Gut Microbiome Following Liraglutide Treatment in Non-diabetic Obese Subjects or Overweight Subjects With Co-morbidities: A Randomised, Double-blind, Placebo Controlled, Parallel Group, Multi-centre, 28-week Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Obesity
Lead sponsor: Xiangya Hospital of Central South University
Sponsor class: OTHER
First posted: 2020-08-25
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We performed a multicenter, randomized, double-blind, placebo-controlled 28-week trial. 300 non-diabetic obese subjects or overweight subjects with co-morbidities were randomly assigned. Eligible participants were randomized 2:1 to once-daily subcutaneous injections of either liraglutide or placebo. The primary outcome is to investigate the composition of the gut microbiota from baseline to end of treatment.

Detailed description: We performed a multicenter, randomized, double-blind, placebo-controlled 28-week trial. 300 individuals (18-75 years of age, body-mass index ≥30 kg/m2 or BMI 27-30kg/m2 accompanied by at least one weight-related complication (treated or untreated hypertension, dyslipidemia, pre-diabetes)) were randomly assigned. All the patients provided written informed consent before participation. Key exclusion criteria were type 1 or 2 diabetes, the use of medications that cause clinically significant weight gain or loss, previous bariatric surgery, a history of pancreatitis, a history of major depressive or other severe psychiatric disorders, and a family or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma. Eligible participants were randomized 2:1 to once-daily subcutaneous injections of either liraglutide or placebo using a computer-generated, centrally administered procedure. Patients, investigators, and the sponsor were unaware of the study-group assignments. The primary outcome is to investigate the composition of the gut microbiota from baseline to end of treatment.

Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activity takes place
* Obesity (BMI ≥30.0 kg/m2); or overweight (BMI ≥27.0 kg/m2) with treated or untreated co-morbid dyslipidemia (Low-density lipoprotein ≥3.38mmol/l (130 mg/dl), or triglycerides ≥1.7mmol/l (150 mg/dl), or high-density lipoprotein \<1.04mmol/l (40 mg/dl) for males and \<1.30mmol/l (50 mg/dl) for females) and/or hypertension (Systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg)
* Age ≥18 years, ≤75 years

Exclusion Criteria:

* Diagnosis of type 1 or type 2 diabetes per the judgment of the investigator
* HbA1c ≥6.5% or fasting plasma glucose ≥7.0 mmol/l or 2-hour post-challenge plasma glucose ≥11.1 mmol/liter (at screening)
* less than 5 kg self-reported change during the previous 3 months
* Previous treatment with GLP-1 receptor agonists (including liraglutide or exenatide) within the last 3 months
* Known or suspected hypersensitivity to trial product, related products or other GLP-1 receptor agonist
* Diet attempts using herbal supplements or over-the-counter medications within 1 months before screening, or use prescription drugs for weight loss within 3 months before screening (for example: orlistat, fenfluramine, maindole ) Or lipid dissolving injection (for example: lipolysis needle) treatment
* Current or history of treatment with medications that may cause significant weight gain, within 3 months prior to screening, including systemic corticosteroids (more than 1 week),tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g. imipramine, amitriptiline, mirtazapin, paroxetine, phenelzine, clorpromazine, thioridazine, clozapine, lanzapine, valproic acid and its derivatives, and lithium)
* A history of malignant tumors within 5 years before screening (except for fully treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical resection, and ductal carcinoma in situ after radical operation)
* A history of severe heart disease is defined as: decompensated heart insufficiency (NYHA III-IV), and/or a history of unstable angina within 6 months before screening, and a history of myocardial infarction within 12 months
* Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)
* Suffer from gastrointestinal motility disorders or obstruction diseases, such as gastroparesis, gastroesophageal reflux disease
* Any lifetime history of a suicidal attempt or A history of any suicidal behavior in the last month prior to randomization
* A patient health questionnaire (PHQ-9) score of ≥15
* Montreal Cognitive Assessment Scale (MoCA) score \<26 at screening;
* Any suicidal ideation of type 4 or 5 on the Columbian Suicidality Severity Rating Scale (C-SSRS) in the last month prior to randomization
* Untreated or uncontrolled hypothyroidism/hyperthyroidism defined as thyroid-stimulating hormone \>6 mIU/liter or \<0.4 mIU/liter
* Screening calcitonin ≥50 ng/liter
* Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC) or Personal history of non-familial medullary thyroid carcinoma
* History of chronic pancreatitis or idiopathic acute pancreatitis or amylase ≥ 3 times the upper limit of normal value during screening
* ALT or AST or TBiL\>3 times the upper limit of normal value during screening
* Impaired renal function, defined as serum creatinine level ≥1.5mg/dL (132µmol/L) in men or ≥1.4mg/dL (123µmol/L) in women at screening
* Untreated or uncontrolled severe dyslipidemia, defined as blood LDL-C≥190mg/dl (4.94mmol/L) and/or TG≥500mg/dl (5.65mmol/L) at screening
* Uncontrolled treated/untreated hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg)
* Previous surgical treatment for obesity (excluding liposuction if performed \>1 year before trial entry)
* According to the investigator's judgment, those who have a surgical plan during the trial period (except for minor operations)
* Participated in any weight loss clinical trials within 3 months before screening, and took any experimental drugs within 1 month (Re-screening is allowed once within the limit of the recruitment period)
* Known or suspected abuse of alcohol or narcotics within 6 months
* Poor compliance with restrictions on diet and behavior during screening
* Females of child-bearing potential who are pregnant, breast-feeding
* Participants intend to become pregnant or are not using adequate contraceptive methods or subjects who use hormonal contraceptives
* The investigator considers that it is not suitable for participants (for example, the investigator judges that severe obstructive sleep apnea will cause gastroesophageal reflux).

Primary outcomes:
measure: The composition of the gut microbiota from baseline to end of treatment.
timeFrame: week 28
Secondary outcomes:
Other outcomes:
Locations:
city: Changsha
country: China
facility: Xiangya Hospital of Central South University
state: Hunan
Study officials:
affiliation: Xiangya Hospital of Central South University
name: Jing Wu
role: PRINCIPAL_INVESTIGATOR
References: