Clinical trial NCT03038620: Impact of Liraglutide 3.0 on Body Fat Distribution
Official title: Impact of Liraglutide 3.0 on Body Fat Distribution, Visceral Adiposity, and Cardiometabolic Risk Markers In Overweight and Obese Adults at High Risk for Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Obesity, Visceral
Cardiovascular Diseases
Fat Disorder
Keywords: Obesity
Visceral
Cardiovascular Disease
Fat
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2017-01-31
Enrollment: 235
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study is a clinical study to investigate the efficacy of liraglutide compared to placebo in reducing visceral adiposity measured by MRI in overweight or obese subjects at high risk for cardiovascular disease after 40 weeks on-treatment.

Detailed description: Obesity has long been recognized as a risk factor for all-cause mortality and morbidity, including the development of cardiovascular and metabolic diseases such as coronary artery disease, hypertension, insulin resistance, diabetes, and dyslipidemia. Obesity has recently been formally defined as a chronic disease characterized by pathophysiological processes that result in increased adipose tissue mass and can result in increased morbidity and mortality. Although the health risks associated with obesity are clear, there is an emerging appreciation that obesity per se, as defined by simple anthropometric measures such as waist circumference or body mass index (BMI), is neither necessary nor sufficient to promote cardiometabolic disease and atherosclerotic cardiovascular disease (ASCVD) risk. As a result, BMI alone is an insufficient marker of risk and may not accurately identify individuals at elevated risk for ASCVD. There is a pressing need to more accurately phenotype obesity to identify individuals at elevated risk for ASCVD that may benefit from more intensive preventive and therapeutic strategies

Eligibility criteria: Inclusion Criteria:

* Age ≥ 35 years
* Able to provide informed consent
* BMI ≥ 30 kg/m2 or ≥ 27 kg/m2 with metabolic syndrome
* Metabolic syndrome is defined as at least three of the following:3

  1. waist circumference \> 102 cm (40 in) in men and 88 cm (35 in) in women
  2. triglycerides \> 150 mg/dL or on treatment for hypertriglyceridemia
  3. HDL cholesterol \< 40 mg/dL in men and \< 50 mg/dL in women
  4. blood pressure \> 130/85 mmHg or on treatment for hypertension
  5. fasting glucose \> 100 mg/dL

Exclusion Criteria:

* Treatment with Glucagon-like peptide-1 (GLP-1) receptor agonists (including liraglutide, exenatide or others as they become available), dipeptidyl peptidase 4 (DPP-4) inhibitors or insulin within the last 3 months.
* Receipt of any anti-obesity drug or supplement within 1 month prior to screening for this trial.
* Self-reported or clinically documented history of significant fluctuations (\>5% change) in weight within 3 months prior to screening for this trial.
* History of diabetes mellitus (type 1 or 2) or on treatment with anti-diabetes medication.
* History of chronic pancreatitis or idiopathic acute pancreatitis (current or prior history).
* History of gallbladder disease (cholelithiasis or cholecystitis).
* Chronic kidney disease stage III or greater (eGFR\<60 mL/min).
* Obesity induced by other endocrinologic disorders (e.g. Cushing Syndrome).
* Current or history of treatment with medications that may cause significant weight gain, within 1 month prior to screening for this trial, including systemic corticosteroids (except for a short course of treatment, i.e., 7- 10 days), tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g., imipramine, amitryptiline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and lithium).
* Diet attempts using herbal supplements or over-the-counter medications within 1 month prior to screening for this trial.
* Current participation in an organized weight reduction program or within the last 1 month prior to screening for this trial.
* Participation in a clinical trial within the last 3 months prior to screening for this trial.
* Familial or personal history of multiple endocrine neoplasia type 2 or familial medullary thyroid carcinoma.
* Personal history of non-familial medullary thyroid carcinoma.
* History of Major Depressive Disorder within the last 2 years.
* History of other severe psychiatric disorders, e.g., schizophrenia, bipolar disorder.
* Any lifetime history of a suicide attempt.
* A history of any suicidal behavior in the last month prior to randomization.
* Surgery scheduled for the trial duration period, except for minor surgical procedures, at the discretion of the Investigator.
* Known or suspected hypersensitivity to trial product(s) or related product(s).
* Known or suspected abuse of alcohol or narcotics.
* Language barrier, mental incapacity, unwillingness or inability to understand.
* Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods. These include abstinence and the following methods: diaphragm with spermicide, condom with spermicide (by male partner), intrauterine device, sponge, spermicide, Norplant®, Depo-Provera® or oral contraceptives.

Primary outcomes:
measure: Relative Percent Reduction in Visceral Adipose Tissue Mass Measured by MRI
timeFrame: Baseline, 40 weeks
Secondary outcomes:
measure: Absolute Reduction in Visceral Adipose Tissue Volume
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Body Weight
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Body Weight
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Waist Circumference
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Waist Circumference
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Total Body Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Total Body Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Abdominal Subcutaneous Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Abdominal Subcutaneous Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Lower Body Subcutaneous Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Lower Body Subcutaneous Adipose Tissue
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Liver Fat Percent
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Liver Fat Percent
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Total Body Lean Volume
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Total Body Lean Volume
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Total Thigh Muscle Volume
timeFrame: Baseline, 40 weeks
measure: Absolute Reduction in Total Thigh Muscle Volume
timeFrame: Baseline, 40 weeks
measure: Relative Percent Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent
timeFrame: Baseline,40 weeks
measure: Absolute Reduction in Mean Anterior Thigh Muscle Fat Infiltration Percent
timeFrame: Baseline,40 weeks
measure: Change From Baseline in VAT/SAT Ratio
timeFrame: Baseline, 40 weeks
measure: Change From Baseline in Total Fat/Fat-free Mass Ratio
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in Fasting Blood Glucose
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in Insulin
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in HOMA-IR
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in C-reactive Protein
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in Triglyceride/HDL-C Ratio
timeFrame: Baseline, 40 weeks
measure: Relative Percent Change in Nt-proBNP
timeFrame: Baseline, 40 weeks
measure: Absolute Change in Fasting Blood Glucose
timeFrame: Baseline,40 weeks
measure: Absolute Change in Insulin
timeFrame: Baseline, 40 weeks
measure: Absolute Change in HOMA-IR
timeFrame: Baseline, 40 weeks
measure: Absolute Change in CRP
timeFrame: Baseline, 40 weeks
measure: Absolute Change in Triglyceride/HDL-C Ratio
timeFrame: Baseline, 40 weeks
measure: Absolute Change in Nt-proBNP
timeFrame: Baseline, 40 weeks
measure: Change From Baseline in Heart Rate
timeFrame: Baseline, 40 weeks
measure: Change From Baseline in Blood Pressure
timeFrame: Baseline, 40 weeks
Other outcomes:
measure: On-treatment Time, Weeks
timeFrame: weeks
Locations:
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Parag Joshi, MD
role: PRINCIPAL_INVESTIGATOR
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