Lifestyle Modification and Liraglutide

NCT02911818 | Completed Phase 4 Results

• 1 other identifier: 824806
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity

Outcome Measures

Primary Outcomes (2)

• Percent Change in Baseline Weight

  Randomization and 52 weeks

• Extension Study Primary Outcome: Percent Change in Re-randomization Weight

  Re-randomization and 12 weeks

Secondary Outcomes (32)

• Change in Systolic Blood Pressure

  Randomization and 52 weeks

• Change in Diastolic Blood Pressure

  Randomization and 52 weeks

• Change in Heart Rate

  Randomization and 52 weeks

• Change in Waist Circumference

  Randomization and 52 weeks

• Change in Total Cholesterol

  Randomization and 52 weeks

Study Arms (5)

CMS-Alone

ACTIVE COMPARATOR

Lifestyle counseling, as currently recommended by the CMS.

Behavioral: CMS-recommended lifestyle counseling

CMS-Liraglutide

ACTIVE COMPARATOR

CMS lifestyle counselling plus liraglutide.

Behavioral: CMS-recommended lifestyle counseling; Drug: Liraglutide 3.0mg

Multi-Component Intervention

ACTIVE COMPARATOR

CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.

Behavioral: CMS-recommended lifestyle counseling; Drug: Liraglutide 3.0mg; Other: Portion-Controlled Diet

12-Week Extension Study: Phentermine Group

ACTIVE COMPARATOR

After the 1-year trial, half the participants who join the extension study will be randomized to phentermine 15.0 mg/d in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study.

Drug: Liraglutide 3.0mg; Drug: Phentermine 15 MG; Behavioral: Extension Study CMS-recommended lifestyle counseling

12-Week Extension Study: Placebo Group

ACTIVE COMPARATOR

After the 1-year trial, half the participants who join the extension study will be randomized to placebo in a double-blind fashion, while continuing to take liraglutide. They will also continue to receive monthly lifestyle counseling. To be eligible for the extension study, participants must have been assigned to one of two medication groups in the original study.

Drug: Liraglutide 3.0mg; Drug: Placebo Oral Tablet; Behavioral: Extension Study CMS-recommended lifestyle counseling

Interventions

CMS-recommended lifestyle counseling BEHAVIORAL

21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

CMS-Alone; CMS-Liraglutide; Multi-Component Intervention

Liraglutide 3.0mg DRUG

Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.

Also known as: Saxenda

12-Week Extension Study: Phentermine Group; 12-Week Extension Study: Placebo Group; CMS-Liraglutide; Multi-Component Intervention

Portion-Controlled Diet OTHER

A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.

Multi-Component Intervention

Placebo Oral Tablet DRUG

12-Week Extension Study: Placebo Group

Phentermine 15 MG DRUG

12-Week Extension Study: Phentermine Group

Extension Study CMS-recommended lifestyle counseling BEHAVIORAL

4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

12-Week Extension Study: Phentermine Group; 12-Week Extension Study: Placebo Group

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
• Age ≥ 21 years and ≤ 70 years
• Eligible female patients will be:
• non-pregnant, evidenced by a negative urine dipstick pregnancy test
• non-lactating
• surgically sterile or postmenopausal, or they will agree to continue to use an accepted method of birth control during the study
• Ability to provide informed consent before any trial-related activities
• Participants must:
• have a primary care provider (PCP) who is responsible for providing routine care
• have a reliable telephone service with which to communicate with study staff
• understand and be willing to comply with all study-related procedures and agree to participate in the study by giving written informed consent
• plan to remain in the Philadelphia area for the next 18 months

You may not qualify if:

• Pregnant or nursing, or plans to become pregnant in the next 18 months, or not using adequate contraceptive measures
• Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
• Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
• Type 1 diabetes
• Type 2 diabetes
• A fasting glucose ≥ 126 mg/dl (on second assessment after first elevated value)
• Recent history of cardiovascular disease (e.g., myocardial infarction or stroke within the past 6 months), congestive heart failure, or heart block greater than first degree
• Clinically significant hepatic or renal disease
• Thyroid disease, not controlled
• History of malignancy (except for non-melanoma skin cancer) in past 5 years
• Current major depressive episode, active suicidal ideation, or history of suicide attempts
• Psychiatric hospitalization within the past 6 months
• Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
• Use in past 3 months of medications known to induce significant weight loss (i.e., prescription weight loss medications) or weight gain (e.g., chronic use of oral steroids, second generation antipsychotics)
• Loss of ≥ 10 lb of body weight within the past 3 months

Sponsors & Collaborators

• University of Pennsylvania: lead
• Novo Nordisk A/S: collaborator

Study Sites (1)

University of Pennsylvania Center for Weight and Eating Disorders

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (3)

• Tronieri JS, Wadden TA, Walsh O, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Bakizada ZM, Chao AM. Effects of liraglutide on appetite, food preoccupation, and food liking: results of a randomized controlled trial. Int J Obes (Lond). 2020 Feb;44(2):353-361. doi: 10.1038/s41366-019-0348-6. Epub 2019 Mar 29.

  PMID: 30926955 DERIVED

• Tronieri JS, Wadden TA, Walsh OA, Berkowitz RI, Alamuddin N, Gruber K, Leonard S, Chao AM. Effects of liraglutide plus phentermine in adults with obesity following 1 year of treatment by liraglutide alone: A randomized placebo-controlled pilot trial. Metabolism. 2019 Jul;96:83-91. doi: 10.1016/j.metabol.2019.03.005. Epub 2019 Mar 20.

  PMID: 30902750 DERIVED

• Wadden TA, Walsh OA, Berkowitz RI, Chao AM, Alamuddin N, Gruber K, Leonard S, Mugler K, Bakizada Z, Tronieri JS. Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial. Obesity (Silver Spring). 2019 Jan;27(1):75-86. doi: 10.1002/oby.22359. Epub 2018 Nov 13.

  PMID: 30421856 DERIVED

Related Links

• Center for Weight and Eating Disorders Website

MeSH Terms

Conditions

Obesity

Interventions

Liraglutide; Phentermine

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide 1; Glucagon-Like Peptides; Proglucagon; Gastrointestinal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Thomas Wadden
• Organization: The University of Pennsylvania Center for Weight and Eating Disorders

wadden@pennmedicine.upenn.edu

215-746-5046

Study Officials

• Thomas A Wadden, Ph.D.

  University of Pennsylvania, Center for Weight and Eating Disorders

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: In the 12 week extension study, participants who are eligible will continue to take liraglutide 3.0 mg in an open fashion. Participants will be randomly assigned in a double-blind fashion to placebo or phentermine.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2016
• First Posted: September 22, 2016
• Study Start: September 1, 2016
• Primary Completion: November 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 7, 2019
• Results First Posted: May 7, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)