Study of the Cardiometabolic Effects of Obesity Pharmacotherapy

Phase 4

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

• Registration Number: NCT04575194
• Lead Sponsor: National and Kapodistrian University of Athens

Brief Summary

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.

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 Timeline

• Study Start: 2020-09-08
• Study First Submitted: 2020-09-30
• Status Verified: 2020-10
• Study First Submitted QC: 2020-10-02
• Study First Posted: 2020-10-05
• Last Update Submitted: 2020-10-06
• Last Update Posted: 2020-10-08
• Primary Completion: 2022-09-30
• Study Completion: 2023-05-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 40

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Liraglutide 3 mg	Liraglutide 6 MG/ML [Saxenda]	Patients will be prescribed sc liraglutide 3 mg/day along with a dietary and physical activity intervention.
Naltrexone/bupropion 32/360 mg	Naltrexone-Bupropion Combination	Patients will be prescribed oral naltrexone/bupropion 32/360 mg/day along with a dietary and physical activity intervention.

Primary Outcome Measures

Name	Time	Method
Changes in blood pressure	3 and 6 months	Blood pressure as assessed by 24-hour recording (numerical scale)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

First Department of Propaedeutic Internal Medicine; 🇬🇷 Athens, Greece