Obesity Clinical Trial
— MODELOfficial title:
Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health Outcomes
NCT number | NCT02911818 |
Other study ID # | 824806 |
Secondary ID | |
Status | Completed |
Phase | Phase 4 |
First received | |
Last updated | |
Start date | September 2016 |
Est. completion date | December 2018 |
Verified date | April 2019 |
Source | University of Pennsylvania |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 150 |
Est. completion date | December 2018 |
Est. primary completion date | November 2018 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 21 Years to 70 Years |
Eligibility |
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 |
Country | Name | City | State |
---|---|---|---|
United States | University of Pennsylvania Center for Weight and Eating Disorders | Philadelphia | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
University of Pennsylvania | Novo Nordisk A/S |
United States,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Percent Change in Baseline Weight | Randomization and 52 weeks | ||
Primary | Extension Study Primary Outcome: Percent Change in Re-randomization Weight | Re-randomization and 12 weeks | ||
Secondary | Change in Systolic Blood Pressure | Randomization and 52 weeks | ||
Secondary | Change in Diastolic Blood Pressure | Randomization and 52 weeks | ||
Secondary | Change in Heart Rate | Randomization and 52 weeks | ||
Secondary | Change in Waist Circumference | Randomization and 52 weeks | ||
Secondary | Change in Total Cholesterol | Randomization and 52 weeks | ||
Secondary | Change in LDL Cholesterol | Randomization and 52 weeks | ||
Secondary | Change in HDL Cholesterol | Randomization and 52 weeks | ||
Secondary | Change in Triglycerides | Randomization and 52 weeks | ||
Secondary | Change in C Reactive Protein | Randomization and 52 weeks | ||
Secondary | Change in Fasting Glucose | Randomization and 52 weeks | ||
Secondary | Change in HbA1c | Randomization and 52 weeks | ||
Secondary | Change in Fasting Insulin | Randomization and 52 weeks | ||
Secondary | Change in HOMA-IR | 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 | Randomization and 52 weeks | |
Secondary | Change in 36-Item Short Form Survey (SF-36) - Physical Component Summary | 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. |
Randomization and 52 weeks | |
Secondary | Change 36-Item Short Form Survey (SF-36) - Mental Component Summary | 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. |
Randomization and 52 weeks | |
Secondary | Change in Patient Health Questionnaire (PHQ-9) | 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. | Randomization and 52 weeks | |
Secondary | Extension Study Secondary Outcome: Change in Systolic Blood Pressure | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Diastolic Blood Pressure | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Heart Rate | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Waist Circumference | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Total Cholesterol | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in LDL Cholesterol | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in HDL Cholesterol | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Triglycerides | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in c-Reactive Protein | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Fasting Glucose | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in HbA1c | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in Fasting Insulin | Re-randomization and 12 weeks | ||
Secondary | Extension Study Secondary Outcome: Change in HOMA-IR | 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 | Re-randomization and 12 weeks | |
Secondary | Extension Study Secondary Outcome: SF-36 - Physical Health Component | 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. |
Re-randomization and 12 weeks | |
Secondary | Extension Study Secondary Outcome: SF-36 - Mental Health Component | 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. |
Re-randomization and 12 weeks | |
Secondary | Extension Study Secondary Outcome: Patient Health Questionnaire (PHQ-9) | 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. | Re-randomization and 12 weeks |
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