Lifestyle Modification and Liraglutide — MODEL  

Obesity Clinical Trial

Official title: Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health Outcomes

Status Completed

Clinical Trial Summary

This is a 52 week, single center, open-labeled, randomized controlled trial.

A total of 150 subjects with obesity, who are free of types 1 and 2 diabetes, as well as contraindications to weight loss, will be randomly assigned to one of three treatment groups: 1) lifestyle counseling, as currently recommended by the Centers for Medicare and Medicaid Services (CMS) (i.e., CMS-Alone); 2) CMS lifestyle counseling plus liraglutide (i.e., CMS-Liraglutide); or 3) CMS-Liraglutide plus a portion-controlled diet (i.e., Multi-Component Intervention).

Subjects in all three groups will have 14 brief (15 minute) lifestyle counseling visits the first 24 weeks, followed by monthly visits in weeks 25-52. This is the schedule and duration of counseling visits recommended by CMS. Counseling sessions will be delivered by a physician, nurse practitioner or registered dietitian (RD) working in consultation with the former providers.

Subjects in all three groups also will have brief physician visits at weeks 1, 4, 8, 16, 24, 36, and 52 (total of 7 visits). These visits are needed for subjects in both liraglutide groups to monitor their response to the medication. These visits are included for subjects in CMS-Alone to match the intensity of medical care provided the two other groups.

The primary outcome is % reduction in initial body weight, as measured from randomization to week 52. Secondary outcomes include the proportion of participants who at week 52 lose >5%, >10%, and >15% of initial weight, as well as % reduction in weight at week 24 and the proportion of participants who meet the three categorical weight losses at this time. The secondary efficacy measures include changes (from randomization to week 52) in cardiovascular disease (CVD) risk factors, glycemic control, mood, quality of life, eating behavior, appetite, sleep, and satisfaction with weight loss.

Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

Statistical Analysis. Using a sample size equation for longitudinal clustered samples, a randomization sample of 50 subjects in CMS-Alone, 50 in CMS-Liraglutide, and 50 in the Multi-Component Intervention provides >80% power to detect the two primary contrasts to be statistically significant. This estimate allows for 20% attrition during the 52-week trial, resulting in approximately 40 treatment completers per group. The ITT longitudinal statistical design will further improve power by allowing the inclusion of available data for non-completers and the adjustment of possible variance reducing baseline covariates.

Clinical Trial Description

The addendum to the original 52-week trial, is a 12-week, single center, randomized placebo-controlled, parallel group designed trial. This 12-week extension study is separate from the original 52-week trial and will not affect the outcome or analysis of the 52-week, 3-arm trial.

Participants and investigators will be masked to participants' assignment to phentermine 15 mg/d versus placebo. Participants in both groups will receive liraglutide in an open-label manner.

We anticipate that 23 (of 50) participants from the original CMS-Liraglutide group and 23 (of 50) from the Multi-Component Intervention will be eligible to participate in the extension study and will elect to do so. We anticipate that 20 participants in each group will complete the 12-week extension study and that those who receive liraglutide 3.0 mg plus phentermine 15.0 mg/d will lose, from randomization to week 12, 3.5+3.5% of initial weight, compared with 0.0+0.5% for those assigned to liraglutide plus placebo.

All participants in the extension study will meet with a physician or nurse practitioner at randomization (week 0) and at weeks 2, 4, 8 and 12. On each occasion they will review patients' blood pressure and pulse, assess suicidal ideation, and record and respond appropriately to reports of changes in physical health. As during the 1-year prior trial, brief lifestyle counseling (15 min) will provided at monthly visits (excluding week 2) by the physician or nurse practitioner or by a registered dietitian or behavioral psychologist, working under their supervision. The lifestyle intervention will be the same as that provided during the last 6 months of both the CMS-Liraglutide and Multi-Component interventions.

Following the 12-week randomized trial, phentermine (or placebo) will be terminated, and all participants will continue to receive liraglutide 3.0 mg/d for an additional 8 weeks (i.e., weeks 12-20) and have lifestyle counseling and medical assessments at weeks 16 and 20. Liraglutide 3.0 mg/d will be terminated at week 20, and participants will have a final safety assessment at week 24.

The primary endpoint of the 12-week extension trial is change in body weight (i.e., % reduction in randomization weight), as measured from randomization (week 0) to week 12. Secondary endpoints include the proportion of subjects who lose > 5% or > 10% of initial weight from randomization to week 12, as well as changes from randomization to week 12 in cardiovascular disease (CVD) risk factors (i.e, blood pressure, triglycerides, LDL and HDL cholesterol, and waist circumference), glycemic control (i.e., fasting blood sugar), mood (PHQ-9), quality of life (i.e, SF-36 and IWQOL-Lite), eating behavior (i.e., Eating Inventory, Eating Disorder Examination-Questionnaire, and Yale Food Addiction Scale), appetite (i.e., visual analogue scales), sleep (i.e., Pittsburgh Sleep Quality Index), and weight loss satisfaction. (All of these measures were administered in the original 1-year trial.)

Safety endpoints will include physical examination, adverse events (AEs), standard laboratory tests, and mental health assessed by the Columbia Suicidality Severity Rating Scale (C-SSRS) and Patient Health Questionnaire (PHQ-9).

All data analyses will proceed using the same principles and methods used in the original protocol. ;

Related Conditions & MeSH terms

• Obesity

• NCT number: NCT02911818
• Study type: Interventional
• Source: University of Pennsylvania
• Status: Completed
• Phase: Phase 4
• Start date: September 2016
• Completion date: December 2018