The Effect of Different Diets on Arterial Stiffness in Obese Patients on Liraglutide

Study Overview
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Brief Summary
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In patients initiating Liraglutide for weight management, the objective is to compare the effect of Med diet, high protein/low carbohydrate (HP/LC) diet and low fat (LF) control diet on CV parameters, namely arterial stiffness, measured by carotid-femoral pulse wave velocity (cfPWV), and visceral adipose tissue, in addition to other metabolic indicators.

Detailed Description
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This is a 6-month open label pilot RCT that will be conducted on Lebanese participants with obesity, upon the initiation of Liraglutide for medical weight management, as recommended by their physician. Patients will be randomized to 3 treatment arms: Mediterranean (Med) diet, high protein/ low carbohydrate (HP/LC) diet, and control low fat (LF) diet. While both Med diet and LF diet will be both hypocaloric, allowing the same energy restriction, of 500 Kcal/d, the HP/LC diet will be ad libitum. Participants will be recruited from the Endocrine clinics at AUB-MC (in Building 23 and at the Metabolic and Bariatric Surgery Unit), and from satellite clinics next to AUB- MC. Brochures and posters of the trial will be available in the clinic waiting areas. Patients of both participating and non-participating physicians will be recruited in the study.

Official Title
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The Effect of Mediterranean, Low Carbohydrate/High Protein and Low-fat Diet on Arterial Stiffness in Obese Patients on Liraglutide: a Randomized Controlled Trial

Conditions
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Obesity, Weight Loss

Intervention / Treatment
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* Other: Dietary Intervention Med Diet
* Other: Dietary Intervention HP/LC Diet
* Other: Dietary Intervention LF Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and premenopausal women with obesity defined as BMI ≥ 30 kg/m2 Upon the initiation of Liraglutide (within the first 1-4 weeks) for medical weight management, for clinical purposes, as advised by the primary physician Able to commit for a 6-month trial visits Exclusion Criteria: Pregnant women Patients who are taking or have taken other weight reducing drug therapies in the previous 6 months Patients who have undergone metabolic weight loss surgery Patients known to have diabetes (HbA1c ≥6.5% at screening) Patients with uncontrolled hypertension Patients with cardiac, pulmonary, renal or liver diseases, active cancer or psychiatric diseases Patients with excessive alcohol intake, defined as ≥ 2 glasses per day Patients known to have uncontrolled/ untreated thyroid disorders. Patients with cushing disease or polycystic ovaries, and those with neuro-endocrine or drug induced obesity (such as anti-psychotic, steroids, hormonal therapy): Such patients are resistant to weight loss, and they need treatment of their primary disease and/or cessation of the culprit medication to lose weight Patients with untreated gout Patients who have undergone bariatric surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A computer-generated allocation sequence will be used, with a permuted block randomization (1:1:1). The biostatistician (MB) will generate the randomization sequence and will share it with a trial coordinator (MR) who is independent of the study team. Upon the recruitment of every participant, the study RA will contact the independent trial coordinator to receive the randomization code, in an opaque and sealed envelope. Randomization will take place at 1-30 days after starting Liraglutide. Treatment allocation will be in batches at the end of each month, and therefore allows for group sessions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Mediterranean Diet<br>50 participants will be randomized to this arm. The intervention consists of 5 individual (visits 1,3,5,7,9) and 8 group (visits 1,2,3,4,5,6,7,8) educational sessions on Mediterranean diet in patients on Liraglutide, over a period of 24 weeks. Dietary assessments and adherence questionnaires will be held on several visits to assess adherence. | Other: Dietary Intervention Med Diet<br>* The diet will consist of a calorie-restricted Med diet, with 500 Kcal/d energy restriction. The intervention consists of individual and group educational sessions on Med diet. During the group sessions, the RA will go over the benefits of Med diet, what composition it should have, and how to make appropriate choices for meal planning, in addition to providing food lists, by season. The individual sessions with subjects will also allow to individualize the diet plan.<br>|
| Experimental: High protein/Low Carbohydrate Diet<br>50 participants will be randomized to this arm. The intervention consists of 5 individual (visits 1,3,5,7,9) and 8 group (visits 1,2,3,4,5,6,7,8) educational sessions on HP/LC diet in patients on Liraglutide, over a period of 24 weeks. Dietary assessments and adherence questionnaires will be held on several visits to assess adherence. | Other: Dietary Intervention HP/LC Diet<br>* This is a non-ketogenic diet consisting of ad libitum intake of proteins, fat, and vegetables, with restriction of daily carbohydrates to <130 g/d. The intervention consists of group educational sessions on HP/LC, same as with Med diet (above). The individual sessions with subjects will also allow to individualize the diet plan.<br>|
| Active Comparator: Low Fat Diet<br>50 participants will be randomized to this arm. The intervention consists of 5 individual (visits 1,3,5,7,9) and 8 group (visits 1,2,3,4,5,6,7,8) educational sessions on low fat diet in patients on Liraglutide, over a period of 24 weeks. Dietary assessments and adherence questionnaires will be held on several visits to assess adherence. | Other: Dietary Intervention LF Diet<br>* In this arm, participants will be advised to follow a calorie restricted LF diet with 500 Kcal/d energy restriction. Group and individual educational sessions will be held at the same frequency as the Med and HP/LC diets, and will have a similar content but targeting LF diet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cfPWV measurement and pulse wave analysis (PWA) using SphygmoCorCvMS V9 (AtCor Medical) | Measured by an RA or a technician, based on the American Heart Association Council recommendations on arterial stiffness measurement in research. The distance from the suprasternal notch to the carotid pulse, and to the femoral site on the same side will be measured; the former distance is subtracted from the latter one. Ten seconds of carotid and 10 seconds of femoral arterial waveforms will be recorded, and the average of the data will be obtained for each of the sites. | 6 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body composition - visceral adipose tissue using dual x-ray absorptiometry (DXA) | Measured by an RA or a technician, assessed using dual x-ray absorptiometry (DXA), Hologic machine, version 13.6.0.5, the preferred method for the assessment of body composition. The ISCD recommendations will be followed for body composition measurement. | 6 months after enrollment | 
| Body composition - percent fat-free body mass using dual x-ray absorptiometry (DXA) | Measured by an RA or a technician, assessed using dual x-ray absorptiometry (DXA), Hologic machine, version 13.6.0.5, the preferred method for the assessment of body composition. The ISCD recommendations will be followed for body composition measurement. | 6 months after enrollment | 
| Body composition - percent body fat using dual x-ray absorptiometry (DXA) | Measured by an RA or a technician, assessed using dual x-ray absorptiometry (DXA), Hologic machine, version 13.6.0.5, the preferred method for the assessment of body composition. The ISCD recommendations will be followed for body composition measurement. | 6 months after enrollment |