Weight Loss With Intensive Lifestyle Modifications Plus Bariatric Surgery Versus Liraglutide 3 mg (LETHE)

Intensive Lifestyle Modifications With or Without Liraglutide 3 mg Versus Sleeve Gastrectomy: A 3 Arm Randomized Controlled Pilot Study (LETHE)

Background/Objectives: Only 1% of the clinically eligible subjects receive surgical treatment for their obesity, thus other options should be investigated. In this study we aim to assess the effect of intensive-lifestyle-modification(ILM) with or without Liraglutide-3mg daily versus sleeve-gastrectomy(SG) on BMI at 1-year.

Subjects/Methods: In this study performed in a University Hospital in Italy, non-diabetic patients eligible for bariatric-surgery are recruited from the weight loss clinic and have the option to choose within three possible weight-loss programs up to complete the allocation of 25 subjects in each arm matched by BMI and age. ILM consists in 600kcal very-low-calorie-diet(VLCD) for 1 month followed by 12kcal/kgbw high-protein, high-fat-diet for 11 months plus 30minutes brisk-walk daily and at least 3 hours aerobic-exercise weekly. SG patients have 1-month VLCD and free-diet thereafter. Patients are evaluated at baseline and at 1,3,6,9 and 12months.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Other: lifestyle modification; Drug: LIRAGLUTIDE 3 Mg/0.5 mL (18 Mg/3 mL) SUB-Q PEN INJECTOR (ML); Other: sleeve gastrectomy

Detailed Description

Obesity is associated with major chronic diseases, including type 2 diabetes (T2D) and cardiovascular disease (CVD) 1-3. The number of subjects affected by morbid obesity or class III obesity (BMI≥40 kg/m2) is rapidly increasing 4 and contributed to 20% of the total per capita health-care expenditures in 2000 in the United States 5 .

Subjects with a body mass index (BMI) >40 kg/m2 or >35 kg/m2 in the presence of obesity complications are eligible for bariatric surgery 6 . The mortality rate after bariatric surgery is low, being 0.08% within 30 days and 0.31% after 30 days 7, and bariatric surgery has shown many health benefits including reduction of long term mortality 8 and type 2 diabetes remission (T2D) 9-11., However, due to the perception that bariatric surgery is a risky procedure among the general public and insurance companies or other health care providers only 1% of the clinically eligible subjects receive surgical treatment for their obesity 12.

The largest portion of patients eligible for bariatric surgery but who are not willing to be operated or cannot undergo surgery for other reasons should be offered, however, with other therapeutic options. To this end a pilot study to determine the efficacy of an intensive lifestyle modification (ILM) with or without 3 mg daily Liraglutide versus bariatric surgery with free diet and free physical activity was designed. In the medical arms the patients were also invited to contact the dietitian and the physician every week by email or by phone to assure a tight weight control. The allocation of the patients, all of them eligible for bariatric surgery, was on a voluntary basis, i.e. they were invited to decide their allocation in one of the 3 arms of the study matched by BMI and age.

Liraglutide, a glucagon-like peptide-1 analog, approved for the treatment of obesity at the dose of 3 mg per day and commercialized under the name of Saxenda, was proved to reduce body weight after 56 weeks by 8.4±7.3 kg as compared with a mean of 2.8±6.5 kg in the patients under placebo 13 . Importantly, the weight reduction is maintained up to 3 years as shown by LeRoux et al. 14.

However, this degree of weight loss is generally considered insufficient by patients who would like to be considered for bariatric surgery.

A 12 week VLCD was reported to allow a weight reduction of about 20 kg in men and of near 16 kg in women 15. However, the weight-reducing effect of a VLCD is temporary and must be combined with other methods to maintain the weight loss. Low-carbohydrate, high-fat, high-protein diet is associated with a relevant weight loss and elevated satiating effects as well as with maintenance or accretion of lean body mass 16,17.

In this study it was hypothesized that a VLCD for 1 month might match in the two medical arms the weight loss reached with SG, thus giving more motivation to the patients to continue the diet. The aim of the study is to find other avenues than bariatric surgery to treat obese patients obtaining a relevant weight loss that can satisfy morbidly obese subjects.

Therefore, this trial included a VLCD for the first month in order to match the diet usually prescribed after bariatric surgery and the following diet will be a low-carbohydrate, high-fat, high-protein diet to achieve a substantial weight loss.

Among the surgical procedures sleeve gastrectomy (SG) was chosen since it has increased markedly in the past few years and has earned a place as a primary bariatric surgery 18.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Catholic University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Age ranging from 18 to 70 years, stable body weight in the previous 6 months body mass index (BMI expressed in kg/m2) >35 if comorbidity (hypertension, sleep apnea, severe hip or knee arthritis) are present or >40 kg/m2.

Exclusion Criteria:

Type 1 or 2 diabetes, previous bariatric surgery, a history of pancreatitis, a history of major depressive or other severe psychiatric disorders, a family or personal history of multiple endocrine cancer type 2 or familial medullary thyroid carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Lifestyle modification; 1 month of a VLCD with 865 kcal per day followed by a 12 kcal per kg of body weight of a high-protein, high fat diet for 11 months in association with intensive	Other: lifestyle modification
EXPERIMENTAL: Lifestyle modification plus Liraglutide 3 mg; 1 month of a VLCD with 865 kcal per day followed by a 12 kcal per kg of body weight of a high-protein, high fat diet for 11 months in association with intensive. The patients will also receive Liraglutide 3 mg daily sc.	Other: lifestyle modification; Drug: LIRAGLUTIDE 3 Mg/0.5 mL (18 Mg/3 mL) SUB-Q PEN INJECTOR (ML)
ACTIVE_COMPARATOR: Sleeve Gastrectomy; The patients will undergo laparoscopic sleeve gastrectomy	Other: sleeve gastrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of baseline BMI	percent variation of BMI with respect to baseline value	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
changes of baseline weight plasma	percent variation of variables with respect to baseline value	1 year
changes in body composition	percent variation of variables with respect to baseline value	1 year
changes in plasma glucose	percent variation of variables with respect to baseline value	1 year
changes in HOMA-IR	percent variation of variables with respect to baseline value	1 year
changes in blood pressure	percent variation of variables with respect to baseline value	1 year
changes in lipid profile	percent variation of variables with respect to baseline value	1 year

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 2, 2015
• Primary Completion (ACTUAL): January 31, 2017
• Study Completion (ACTUAL): April 10, 2017

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: May 22, 2018
• First Posted (ACTUAL): May 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 23, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: obesity; liraglutide; Weight-loss; sleeve-gastrectomy
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: 0002017056

Drug and device information, study documents

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