Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Lifestyle Modification and Liraglutide (MODEL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02911818
Recruitment Status : Completed
First Posted : September 22, 2016
Results First Posted : May 7, 2019
Last Update Posted : May 7, 2019
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
University of Pennsylvania

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.


Condition or disease Intervention/treatment Phase
Obesity Behavioral: CMS-recommended lifestyle counseling Drug: Liraglutide 3.0mg Other: Portion-Controlled Diet Drug: Placebo Oral Tablet Drug: Phentermine 15 MG Behavioral: Extension Study CMS-recommended lifestyle counseling Phase 4

Detailed 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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health Outcomes
Actual Study Start Date : September 2016
Actual Primary Completion Date : November 2018
Actual Study Completion Date : December 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight
Drug Information available for: Liraglutide

Arm Intervention/treatment
Active Comparator: CMS-Alone
Lifestyle counseling, as currently recommended by the CMS.
Behavioral: CMS-recommended lifestyle counseling
21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

Active Comparator: CMS-Liraglutide
CMS lifestyle counselling plus liraglutide.
Behavioral: CMS-recommended lifestyle counseling
21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

Drug: Liraglutide 3.0mg
Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.
Other Name: Saxenda

Active Comparator: Multi-Component Intervention
CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.
Behavioral: CMS-recommended lifestyle counseling
21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

Drug: Liraglutide 3.0mg
Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.
Other Name: Saxenda

Other: Portion-Controlled Diet
A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks.

Active Comparator: 12-Week Extension Study: Phentermine Group
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
Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.
Other Name: Saxenda

Drug: Phentermine 15 MG
Behavioral: Extension Study CMS-recommended lifestyle counseling
4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.

Active Comparator: 12-Week Extension Study: Placebo Group
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
Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection.
Other Name: Saxenda

Drug: Placebo Oral Tablet
Behavioral: Extension Study CMS-recommended lifestyle counseling
4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian.




Primary Outcome Measures :
  1. Percent Change in Baseline Weight [ Time Frame: Randomization and 52 weeks ]
  2. Extension Study Primary Outcome: Percent Change in Re-randomization Weight [ Time Frame: Re-randomization and 12 weeks ]

Secondary Outcome Measures :
  1. Change in Systolic Blood Pressure [ Time Frame: Randomization and 52 weeks ]
  2. Change in Diastolic Blood Pressure [ Time Frame: Randomization and 52 weeks ]
  3. Change in Heart Rate [ Time Frame: Randomization and 52 weeks ]
  4. Change in Waist Circumference [ Time Frame: Randomization and 52 weeks ]
  5. Change in Total Cholesterol [ Time Frame: Randomization and 52 weeks ]
  6. Change in LDL Cholesterol [ Time Frame: Randomization and 52 weeks ]
  7. Change in HDL Cholesterol [ Time Frame: Randomization and 52 weeks ]
  8. Change in Triglycerides [ Time Frame: Randomization and 52 weeks ]
  9. Change in C Reactive Protein [ Time Frame: Randomization and 52 weeks ]
  10. Change in Fasting Glucose [ Time Frame: Randomization and 52 weeks ]
  11. Change in HbA1c [ Time Frame: Randomization and 52 weeks ]
  12. Change in Fasting Insulin [ Time Frame: Randomization and 52 weeks ]
  13. Change in HOMA-IR [ Time Frame: Randomization and 52 weeks ]
    HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

  14. Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary [ Time Frame: Randomization and 52 weeks ]

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.

    Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.

    Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.


  15. Change 36-Item Short Form Survey (SF-36) - Mental Component Summary [ Time Frame: Randomization and 52 weeks ]

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.

    Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.

    Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.


  16. Change in Patient Health Questionnaire (PHQ-9) [ Time Frame: Randomization and 52 weeks ]
    PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.

  17. Extension Study Secondary Outcome: Change in Systolic Blood Pressure [ Time Frame: Re-randomization and 12 weeks ]
  18. Extension Study Secondary Outcome: Change in Diastolic Blood Pressure [ Time Frame: Re-randomization and 12 weeks ]
  19. Extension Study Secondary Outcome: Change in Heart Rate [ Time Frame: Re-randomization and 12 weeks ]
  20. Extension Study Secondary Outcome: Change in Waist Circumference [ Time Frame: Re-randomization and 12 weeks ]
  21. Extension Study Secondary Outcome: Change in Total Cholesterol [ Time Frame: Re-randomization and 12 weeks ]
  22. Extension Study Secondary Outcome: Change in LDL Cholesterol [ Time Frame: Re-randomization and 12 weeks ]
  23. Extension Study Secondary Outcome: Change in HDL Cholesterol [ Time Frame: Re-randomization and 12 weeks ]
  24. Extension Study Secondary Outcome: Change in Triglycerides [ Time Frame: Re-randomization and 12 weeks ]
  25. Extension Study Secondary Outcome: Change in c-Reactive Protein [ Time Frame: Re-randomization and 12 weeks ]
  26. Extension Study Secondary Outcome: Change in Fasting Glucose [ Time Frame: Re-randomization and 12 weeks ]
  27. Extension Study Secondary Outcome: Change in HbA1c [ Time Frame: Re-randomization and 12 weeks ]
  28. Extension Study Secondary Outcome: Change in Fasting Insulin [ Time Frame: Re-randomization and 12 weeks ]
  29. Extension Study Secondary Outcome: Change in HOMA-IR [ Time Frame: Re-randomization and 12 weeks ]
    HOMA-IR is a measurement for insulin resistance and is calculated from: fasting insulin (U/L) x fasting glucose (mg/dL)/405. A decrease from baseline to the end of treatment, a negative value, indicates an improvement

  30. Extension Study Secondary Outcome: SF-36 - Physical Health Component [ Time Frame: Re-randomization and 12 weeks ]

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.

    Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.

    Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.


  31. Extension Study Secondary Outcome: SF-36 - Mental Health Component [ Time Frame: Re-randomization and 12 weeks ]

    All sub scales are scored from 0 - 100, with higher scores indicating better health. Each component summary is a normed score with a mean of 50 and standard deviation of 10 in the US general population. Higher scores indicate better health.

    Z-scores are computed for each subscale, which are then converted into a component summary z-score using a weighted formula. The component summary z-score is then converted to a t-distribution with a mean of 50 and standard deviation of 10.

    Scores are scaled to a T-score with a mean of 50 and standard deviation of 10. Scores above 50 indicate better health.


  32. Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9) [ Time Frame: Re-randomization and 12 weeks ]
    PHQ-9 is scored based on a 0-27 scale in which higher scores indicate more severe depression. Values are summed to compute the total score.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
  2. Age ≥ 21 years and ≤ 70 years
  3. 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
  4. Ability to provide informed consent before any trial-related activities
  5. 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

Exclusion Criteria:

  1. Pregnant or nursing, or plans to become pregnant in the next 18 months, or not using adequate contraceptive measures
  2. Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
  3. Uncontrolled hypertension (systolic blood pressure ≥ 160 mm Hg or diastolic blood pressure ≥ 100 mm Hg)
  4. Type 1 diabetes
  5. Type 2 diabetes
  6. A fasting glucose ≥ 126 mg/dl (on second assessment after first elevated value)
  7. 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
  8. Clinically significant hepatic or renal disease
  9. Thyroid disease, not controlled
  10. History of malignancy (except for non-melanoma skin cancer) in past 5 years
  11. Current major depressive episode, active suicidal ideation, or history of suicide attempts
  12. Psychiatric hospitalization within the past 6 months
  13. Self-reported alcohol or substance abuse within the past 12 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
  14. 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)
  15. Loss of ≥ 10 lb of body weight within the past 3 months
  16. History of (or plans for) bariatric surgery
  17. Inability to walk 5 blocks comfortably or engage in some other form of aerobic activity (e.g., swimming)
  18. Known or suspected allergy to trial medication(s), excipients, or related products
  19. Hypersensitivity to liraglutide or any product components
  20. The receipt of any investigational drug within 6 months prior to this trial
  21. Previous participation in this trial (e.g., randomized and failed to participate)
  22. History of pancreatitis
  23. Subjects will be included/excluded according to the latest updated US PI.

12-Week Extension Trial:

Inclusion Criteria

Inclusion criteria are those described for the original 1-year trial (enumerated above). The principal exception from these criteria is that participants will only be required to have a BMI > 27 kg/m2, with or without co-morbidities, to be eligible to participate in the extension study. All participants will have met BMI inclusion criteria when they initiated the use of liraglutide and now will use it, potentially with phentermine 15 mg/d, to facilitate to the maintenance of lost weight. (Liraglutide is approved for chronic weight management, including following successful weight loss.) We do not wish to enroll participants with a BMI < 27 kg/m2 because of the possibility that they could reduce substantially below a BMI of 24.9 kg/m2, the upper limit of "normal" weight.

Exclusion Criteria:

Exclusion criteria will include those listed in the original protocol, including those specific to the use of liraglutide 3.0 mg/d (e.g., family history of medullary thyroid cancer).

Additional exclusion criteria added to the 12-week extension study are specific to the use of phentermine 15 mg/d. They include:

  1. Use of monoamine oxidase inhibitors in the past 2 weeks
  2. Glaucoma
  3. Presence or history of marked agitation
  4. History of drug abuse
  5. Known hypersensitivity to sympathomimetic amines
  6. Current use of selective serotonin re-uptake inhibitors (e.g., fluoxetine, sertraline, etc)
  7. Current use of any other weight loss medications (besides liraglutide 3.0 mg/d)
  8. History of coronary artery disease

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02911818


Locations
Layout table for location information
United States, Pennsylvania
University of Pennsylvania Center for Weight and Eating Disorders
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
Novo Nordisk A/S
Investigators
Layout table for investigator information
Principal Investigator: Thomas A Wadden, Ph.D. University of Pennsylvania, Center for Weight and Eating Disorders
  Study Documents (Full-Text)

Documents provided by University of Pennsylvania:
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02911818    
Other Study ID Numbers: 824806
First Posted: September 22, 2016    Key Record Dates
Results First Posted: May 7, 2019
Last Update Posted: May 7, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Liraglutide
Phentermine
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Central Nervous System Stimulants
Appetite Depressants
Anti-Obesity Agents
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action