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

• ClinicalTrials.gov Identifier: NCT04990024
• Recruitment Status: Recruiting
• First Posted: August 4, 2021
• Last Update Posted: July 20, 2022
• Sponsor: American University of Beirut Medical Center
• Information provided by (Responsible Party): Marlene Chakhtoura, American University of Beirut Medical Center

Tracking Information

• First Submitted Date: July 2, 2021
• First Posted Date: August 4, 2021
• Last Update Posted Date: July 20, 2022
• Actual Study Start Date: July 1, 2021
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 26, 2021)

cfPWV measurement and pulse wave analysis (PWA) using SphygmoCorCvMS V9 (AtCor Medical) [ Time Frame: 6 months after enrollment ]

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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 26, 2021)

• Body composition - visceral adipose tissue using dual x-ray absorptiometry (DXA) [ Time Frame: 6 months after enrollment ]
  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.
• Body composition - percent fat-free body mass using dual x-ray absorptiometry (DXA) [ Time Frame: 6 months after enrollment ]
  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.
• Body composition - percent body fat using dual x-ray absorptiometry (DXA) [ Time Frame: 6 months after enrollment ]
  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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: August 4, 2021)

• Dietary Assessment using 24-hour recalls [ Time Frame: 6 months after enrollment ]
  Three-repeated 24-hour recalls (24 HR) administered via phone (2-week days and one week-end day, during one specific week). During the phone call, the participant will be asked to recall all what she/he has consumed during the past 24 hours, and the multiple pass approach of the USDA will be adopted.
• Dietary Assessment using adherence questionnaires [ Time Frame: 6 months after enrollment ]
  During the individual sessions, brief adherence assessment questionnaires for each diet, adapted from PREDIMED protocol, will be administered to calculate dietary adherence scores.
• Anthropometric measurements - weight in kilograms, height in centimetres, aggregated into BMI (kilogram per meter squared). [ Time Frame: 6 months after enrollment ]
  Weight and height will be measured following standard operating procedures (SOP) and BMI will be computed by dividing weight by height squared.
• Anthropometric measurements - waist and hip circumference in centimetres, aggregated into waist to hip ratio ratio [ Time Frame: 6 months after enrollment ]
  Waist and hip circumference will be measured following standard operating procedures (SOP).
• Vital signs - blood pressure [ Time Frame: 6 months after enrollment ]
  Blood pressure will be measured following standard operating procedures (SOP).
• Vital signs - heart rate [ Time Frame: 6 months after enrollment ]
  Heart rate will be measured following standard operating procedures (SOP).
• Genetic studies [ Time Frame: 6 months after enrollment ]
  Genetic studies will consist of Single Nucleoside Polymorphism (SNP) analysis of genes of the GLP1 receptors and cannabinoid receptor 1 will be performed in the molecular lab. These tests will be run at the endocrine core research Lab in batches at study completion.
• Metabolic, inflammatory and appetite hormones in pg/mL [ Time Frame: 6 months after enrollment ]
  Gastric inhibitory polypeptide (GIP), Leptin, Adiponectin, Orexin, IL6. These tests will be run at the endocrine core research Lab in batches at study completion.
• Metabolic, inflammatory and appetite hormones in pmol/L [ Time Frame: 6 months after enrollment ]
  Insulin and Ghrelin.These tests will be run at the endocrine core research Lab in batches at study completion.
• Metabolic, inflammatory and appetite hormones in ng/mL [ Time Frame: 6 months after enrollment ]
  Irisin and mineral hormones and markers, including Crosslaps, Osteocalcin, GLP1. These tests will be run at the endocrine core research Lab in batches at study completion.
• Quality of Life Measurement as assessed by the SF-36 questionnaire [ Time Frame: 6 months after enrollment ]
  SF-36 questionnaire filled by participant

Original Other Pre-specified Outcome Measures (submitted: July 26, 2021)

• Dietary Assessment using 24-hour recalls [ Time Frame: 6 months after enrollment ]
  Three-repeated 24-hour recalls (24 HR) administered via phone (2-week days and one week-end day, during one specific week). During the phone call, the participant will be asked to recall all what she/he has consumed during the past 24 hours, and the multiple pass approach of the USDA will be adopted.
• Dietary Assessment using adherence questionnaires [ Time Frame: 6 months after enrollment ]
  During the individual sessions, brief adherence assessment questionnaires for each diet, adapted from PREDIMED protocol, will be administered to calculate dietary adherence scores.
• Anthropometric measurements - weight in kilograms, height in centimetres, aggregated into BMI (kilogram per meter squared). [ Time Frame: 6 months after enrollment ]
  Weight and height will be measured following standard operating procedures (SOP) and BMI will be computed by dividing weight by height squared.
• Anthropometric measurements - waist and hip circumference in centimetres, aggregated into waist to hip ratio ratio [ Time Frame: 6 months after enrollment ]
  Waist and hip circumference will be measured following standard operating procedures (SOP).
• Vital signs - blood pressure [ Time Frame: 6 months after enrollment ]
  Blood pressure will be measured following standard operating procedures (SOP).
• Vital signs - heart rate [ Time Frame: 6 months after enrollment ]
  Heart rate will be measured following standard operating procedures (SOP).
• Genetic studies [ Time Frame: 6 months after enrollment ]
  Genetic studies will consist of Single Nucleoside Polymorphism (SNP) analysis of genes of the GLP1 receptors and cannabinoid receptor 1 will be performed in the molecular lab. These tests will be run at the endocrine core research Lab in batches at study completion.
• Metabolic, inflammatory and appetite hormones [ Time Frame: 6 months after enrollment ]
  Gastric inhibitory polypeptide (GIP), Leptin, Adiponectin, Irisin, Insulin, Ghrelin, Orexin, IL6, and mineral hormones and markers, including Crosslaps, Osteocalcin, GLP1. These tests will be run at the endocrine core research Lab in batches at study completion.
• Quality of Life Measurement [ Time Frame: 6 months after enrollment ]
  SF-36 questionnaire

Descriptive Information

• Brief Title: The Effect of Different Diets on Arterial Stiffness in Obese Patients on Liraglutide
• Official Title: The Effect of Mediterranean, Low Carbohydrate/High Protein and Low-fat Diet on Arterial Stiffness in Obese Patients on Liraglutide: a Randomized Controlled Trial
• Brief Summary: 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: 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.
• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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)
Masking Description:

The design is open label as it is impossible to blind the participants and the research team for the study intervention. Each of the dietary interventions will be delivered in the format of intensive, individual and group sessions about the diet, food selection and food recipes.

Primary Purpose: Treatment

Condition

• Obesity
• Weight Loss

Intervention

• Other: Dietary Intervention Med Diet
  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.
• Other: Dietary Intervention HP/LC Diet
  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.
• Other: Dietary Intervention LF Diet
  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.

Study Arms

• Experimental: Mediterranean Diet
  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.
  Intervention: Other: Dietary Intervention Med Diet
• Experimental: High protein/Low Carbohydrate Diet
  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.
  Intervention: Other: Dietary Intervention HP/LC Diet
• Active Comparator: Low Fat Diet
  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.
  Intervention: Other: Dietary Intervention LF Diet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 26, 2021): 150
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 15, 2023
• Estimated Primary Completion Date: June 15, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Contacts

Contact: Marlene Chakhtoura, MD, MSc; +9611350000 ext 7411; mc39@aub.edu.lb

Contact: Rachelle El Haber, BSc; +9611350000 ext 8314; re136@aub.edu.lb

• Listed Location Countries: Lebanon

Administrative Information

• NCT Number: NCT04990024
• Other Study ID Numbers: BIO-2020-0136
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Marlene Chakhtoura, American University of Beirut Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: American University of Beirut Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Marlene Chakhtoura, MD, MSc; American University of Beirut Medical Center

• PRS Account: American University of Beirut Medical Center
• Verification Date: July 2022