Study of the Cardiometabolic Effects of Obesity Pharmacotherapy

Cardiovascular and Metabolic Effects of Drugs for the Treatment of Obesity

The aim of the present study is to compare the efficacy of liraglutide vs. naltrexone/bupropion on metabolic and cardiovascular risk markers, weight loss, as well as the postprandial secretion of gastrointestinal hormones involved in hunger and satiety, after a test meal. The study will include 40 patients, who will further be divided into two treatment groups (20 patients on liraglutide vs. 20 patients on naltrexone/bupropion). The patients will be examined at baseline, 3 and 6 months after the treatment initiation.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Blood Pressure
• Intervention / Treatment: Drug: Liraglutide 6 MG/ML [Saxenda]; Drug: Naltrexone-Bupropion Combination

Detailed Description

This is a prospective study of patients aged ≥18 years, who are overweight (BMI ≥ 27 kg / m2 in the presence of dyslipidemia or hypertension or obstructive sleep apnea or fatty infiltration or prediabetes) or obese patients (BMI ≥ 30 kg / m2). Patients' data will be collected before starting medication (time 0) and at 3 and 6 months under treatment in the clinical practice of the selected drug, as described in the drug's package leaflet, along with a simultaneous dietary intervention and exercise. Patient groups will be comparable in age, gender and BMI.

The aim of the study is the comparison of the efficacy of liraglutide vs. naltrexone/bupropion in metabolic and cardiovascular markers.

The following parameters will be measured:

• Weight, height, waist and hip circumference
• 24-hour recording of blood pressure and heart rate
• HbA1c, total cholesterol, LDL, HDL, urine albumin/creatinine ratio
• Bioelectric impedance for determination of total and visceral fat and muscle mass Indirect calorimetry for the determination of resting metabolic rate and total energy expenditure
• Determination of baroreflex sensitivity (BRS) and heart rate variability (HRV) to investigate the function of the autonomic nervous system
• Blood sample test meal at 0, 30, 60, 90, 120, 150 and 180 min to determine insulin concentration and gastrointestinal hormones involved in hunger and satiety with modern indirect calorimetry to determine postprandial thermogenic analog scales (VAS)
• Neuropathy tests
• Assessment of quality of life with the SF-36 questionnaire and assessment of the feeling of hunger and satiety
• Echocardiographic determination of the left systolic and telodiastolic diameter of the left ventricle, cardiac fat and the Tei index at times 0 and 6 months with medication
• Pericardial fat

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Alexandros Kokkinos, MD, PhD; Phone Number: +302132061248; Email: rjd@otenet.gr
• Study Contact Backup: Name: Georgia Argyrakopoulou, MD, PhD, MSc; Phone Number: +306972284033; Email: gargyrakopoulou@gmail.com

Study Locations

• Greece
  • Athens, Greece, 11527
    • Recruiting
    • First Department of Propaedeutic Internal Medicine
    • Contact: Alexandros Kokkinos, MD, PhD; Phone Number: 2132061248; Email: rjd@otenet.gr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years with BMI ≥ 30 kg / m2 or BMI ≥ 27 kg / m2 in the presence of dyslipidemia or hypertension or obstructive sleep apnea or fatty infiltration or prediabetes.

Exclusion Criteria:

1. Presence of any clinical contraindications for the administration of liraglutide or bupropion / naltrexone
2. Bariatric surgery
3. Diabetes type 2
4. Active malignancy
5. Medication that affects weight (eg corticosteroids, phenothiazines)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liraglutide 3 mg; Patients will be prescribed sc liraglutide 3 mg/day along with a dietary and physical activity intervention.	Drug: Liraglutide 6 MG/ML [Saxenda]; 3 mg of sc liraglutide daily plus lifestyle intervention
Active Comparator: Naltrexone/bupropion 32/360 mg; Patients will be prescribed oral naltrexone/bupropion 32/360 mg/day along with a dietary and physical activity intervention.	Drug: Naltrexone-Bupropion Combination; 32/360 mg of oral lnaltrexone-bupropion daily plus lifestyle intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in blood pressure	Blood pressure as assessed by 24-hour recording (numerical scale)	3 and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight loss	Percentage of weight lost will be measured by an electronic scale (numerical scale)	3 and 6 months
Changes in glycemic	Measurement of HbA1c will be measured biochemically (numerical scale)	3 and 6 months
Changes in lipemic profile	Total cholesterol, Triglycerides, LDL-C, HDL-C will be measured biochemically (numerical scale)	3 and 6 months
Percentage of visceral fat	Measurement of visceral fat by bioimpedance analysis (numerical scale)	3 and 6 months
Fat mass	Measurement of fat mass by bioimpedance analysis (numerical scale)	3 and 6 months
Fat free mass	Measurement of fat free mass by bioimpedance analysis (numerical scale)	3 and 6 months
Autonomic nervous system function	Measurement of heart rate variability will be measured through Ewing score and Spectral analysis testing (numerical scale)	3 and 6 months
Changes in meal induced thermogenesis	Measurement through indirect calorimetry and assessment of changes in Resting Metabolic Rate (RMR) (numerical scale)	3 and 6 months
Changes in gut hormones involved in appetite regulation	Measurement in plasma before and after the intervention during a mixed meal test will be measured through ELISA kits (numerical scale)	3 and 6 months

Collaborators and Investigators

• Sponsor: National and Kapodistrian University of Athens
• Collaborators: Athens Medical Center
• Investigators: Principal Investigator: Alexandros Kokkinos, MD, PhD, National and Kapodistrian University of Athens

Study record dates

Study Major Dates

• Study Start (Actual): September 8, 2020
• Primary Completion (Anticipated): September 30, 2022
• Study Completion (Anticipated): May 30, 2023

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): October 8, 2020
• Last Update Submitted That Met QC Criteria: October 6, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Sensory System Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Narcotic Antagonists; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Incretins; Alcohol Deterrents; Dopamine Uptake Inhibitors; Liraglutide; Naltrexone; Bupropion
• Other Study ID Numbers: Obesity drugs study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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