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| Name | Class |
|---|---|
| Novo Nordisk A/S | INDUSTRY |
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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| CMS-Alone | Active Comparator | Lifestyle counseling, as currently recommended by the CMS. |
|
| CMS-Liraglutide | Active Comparator | CMS lifestyle counselling plus liraglutide. |
|
| Multi-Component Intervention | Active Comparator | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks. |
|
| 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. |
|
| 12-Week Extension Study: Placebo Group |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| CMS-recommended lifestyle counseling | Behavioral | 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percent Change in Baseline Weight | Randomization and 52 weeks | |
| Extension Study Primary Outcome: Percent Change in Re-randomization Weight | Re-randomization and 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Systolic Blood Pressure | Randomization and 52 weeks | |
| Change in Diastolic Blood Pressure | Randomization and 52 weeks | |
| Change in Heart Rate |
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Inclusion Criteria:
Participants must have a BMI ≥ 30 and ≤ 55 kg/m²
Age ≥ 21 years and ≤ 70 years
Eligible female patients will be:
Ability to provide informed consent before any trial-related activities
Participants must:
Exclusion Criteria:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Thomas A Wadden, Ph.D. | University of Pennsylvania, Center for Weight and Eating Disorders | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania Center for Weight and Eating Disorders | Philadelphia | Pennsylvania | 19104 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30926955 | Derived | 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. | |
| 30902750 | Derived |
| Label | URL |
|---|---|
| Center for Weight and Eating Disorders Website | View source |
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This trial enrolled 150 participants for the original 52-week study. The 12-week extension study randomized 45 participants from the 100 eligible from the original 52-week trial who were originally in either the CMS-Liraglutide or Multi-Component groups. Eligible participants for the 12-week extension had to complete 1 year on liraglutide.
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| ID | Title | Description |
|---|---|---|
| FG000 | CMS-Alone | Lifestyle counseling on the visit schedule recommended by the Centers for Medicare and Medicaid Services (CMS). CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. |
| FG001 | CMS-Liraglutide | CMS lifestyle counselling plus liraglutide 3.0 mg/d. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. |
| FG002 | Multi-Component Intervention | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Portion-Controlled Diet: A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks, beginning at week 4. |
| FG003 | 12-Week Extension Study: Phentermine Group | After the 1-year trial, half the participants who elect to 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: 4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Phentermine 15 MG |
| FG004 | 12-Week Extension Study: Placebo Group | After the 1-year trial, half the participants who elect to 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: 4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Placebo Oral Tablet |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 52 Week Study |
| |||||||||||||
| 12 Week Extension Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | CMS-Alone | Lifestyle counseling, on the visit schedule currently recommended by the CMS. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. |
| BG001 | CMS-Liraglutide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percent Change in Baseline Weight | Posted | Mean | Standard Error | percent change | Randomization and 52 weeks |
|
52-weeks post randomization for the original trial; 12-weeks for the extension trial post extension randomization
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | CMS-Alone | Lifestyle counseling, as currently recommended by the CMS. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthma Exacerbation | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Thomas Wadden | The University of Pennsylvania Center for Weight and Eating Disorders | 215-746-5046 | wadden@pennmedicine.upenn.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 25, 2018 | Mar 6, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D000069450 | Liraglutide |
| D010645 | Phentermine |
| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
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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.
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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. |
|
| Liraglutide 3.0mg | Drug | Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. |
|
|
| Portion-Controlled Diet | Other | A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks. |
|
| Placebo Oral Tablet | Drug |
|
| Phentermine 15 MG | Drug |
|
| Extension Study CMS-recommended lifestyle counseling | Behavioral | 4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. |
|
| Randomization and 52 weeks |
| Change in Waist Circumference | Randomization and 52 weeks |
| Change in Total Cholesterol | Randomization and 52 weeks |
| Change in LDL Cholesterol | Randomization and 52 weeks |
| Change in HDL Cholesterol | Randomization and 52 weeks |
| Change in Triglycerides | Randomization and 52 weeks |
| Change in C Reactive Protein | Randomization and 52 weeks |
| Change in Fasting Glucose | Randomization and 52 weeks |
| Change in HbA1c | Randomization and 52 weeks |
| Change in Fasting Insulin | Randomization and 52 weeks |
| 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 |
| 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 |
| 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 |
| 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 |
| Extension Study Secondary Outcome: Change in Systolic Blood Pressure | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Diastolic Blood Pressure | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Heart Rate | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Waist Circumference | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Total Cholesterol | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in LDL Cholesterol | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in HDL Cholesterol | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Triglycerides | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in c-Reactive Protein | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Fasting Glucose | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in HbA1c | Re-randomization and 12 weeks |
| Extension Study Secondary Outcome: Change in Fasting Insulin | Re-randomization and 12 weeks |
| 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 |
| 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 |
| 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 |
| 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 |
| 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. |
| 30421856 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
CMS lifestyle counselling plus liraglutide 3.0 mg/d. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. |
| BG002 | Multi-Component Intervention | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Portion-Controlled Diet: A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks, beginning at week 4. |
| BG003 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG002 | Multi-Component Intervention | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg/d: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Portion-Controlled Diet: A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks, beginning at week 4. |
|
|
| Primary | Extension Study Primary Outcome: Percent Change in Re-randomization Weight | Posted | Mean | Standard Error | percent change | Re-randomization and 12 weeks |
|
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|
| Secondary | Change in Systolic Blood Pressure | Posted | Mean | Standard Error | mm Hg | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Diastolic Blood Pressure | Posted | Mean | Standard Error | mm Hg | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Heart Rate | Posted | Mean | Standard Error | Beats per minute | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Waist Circumference | Posted | Mean | Standard Error | cm | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Total Cholesterol | Posted | Mean | Standard Error | mg/dL | Randomization and 52 weeks |
|
|
|
| Secondary | Change in LDL Cholesterol | Posted | Mean | Standard Error | mg/dL | Randomization and 52 weeks |
|
|
|
| Secondary | Change in HDL Cholesterol | Posted | Mean | Standard Error | mg/dL | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Triglycerides | Posted | Mean | Standard Error | mg/dL | Randomization and 52 weeks |
|
|
|
| Secondary | Change in C Reactive Protein | Posted | Mean | Standard Error | mg/L | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Fasting Glucose | Posted | Mean | Standard Error | mg/dL | Randomization and 52 weeks |
|
|
|
| Secondary | Change in HbA1c | Posted | Mean | Standard Error | percentage | Randomization and 52 weeks |
|
|
|
| Secondary | Change in Fasting Insulin | Posted | Mean | Standard Error | uIU/mL | 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 | Posted | Mean | Standard Error | mg/dL*µIU/mL/405 | 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. | Posted | Mean | Standard Error | T scores | 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. | Posted | Mean | Standard Error | T scores | 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. | Posted | Mean | Standard Error | score on a scale | Randomization and 52 weeks |
|
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| Secondary | Extension Study Secondary Outcome: Change in Systolic Blood Pressure | Posted | Mean | Standard Error | mm Hg | Re-randomization and 12 weeks |
|
|
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| Secondary | Extension Study Secondary Outcome: Change in Diastolic Blood Pressure | Posted | Mean | Standard Error | mm Hg | Re-randomization and 12 weeks |
|
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| Secondary | Extension Study Secondary Outcome: Change in Heart Rate | Posted | Mean | Standard Error | Beats per minute | Re-randomization and 12 weeks |
|
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| Secondary | Extension Study Secondary Outcome: Change in Waist Circumference | Posted | Mean | Standard Error | cm | Re-randomization and 12 weeks |
|
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| Secondary | Extension Study Secondary Outcome: Change in Total Cholesterol | Posted | Mean | Standard Error | mg/dL | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in LDL Cholesterol | Posted | Mean | Standard Error | mg/dL | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in HDL Cholesterol | Posted | Mean | Standard Error | mg/dL | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in Triglycerides | Posted | Mean | Standard Error | mg/dL | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in c-Reactive Protein | Posted | Mean | Standard Error | mg/L | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in Fasting Glucose | Posted | Mean | Standard Error | mg/dL | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in HbA1c | Posted | Mean | Standard Error | percentage | Re-randomization and 12 weeks |
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| Secondary | Extension Study Secondary Outcome: Change in Fasting Insulin | Posted | Mean | Standard Error | uIU/mL | Re-randomization and 12 weeks |
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| 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 | Posted | Mean | Standard Error | mg/dL*µIU/mL/405 | Re-randomization and 12 weeks |
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| 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. | Posted | Mean | Standard Error | T scores | Re-randomization and 12 weeks |
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| 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. | Posted | Mean | Standard Error | T scores | Re-randomization and 12 weeks |
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| 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. | Posted | Mean | Standard Error | score on a scale | Re-randomization and 12 weeks |
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| 0 |
| 50 |
| 2 |
| 50 |
| 21 |
| 50 |
| EG001 | CMS-Liraglutide | CMS lifestyle counselling plus liraglutide. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. | 0 | 50 | 0 | 50 | 42 | 50 |
| EG002 | Multi-Component Intervention | CMS-Liraglutide plus a 1000-1200 kcal/day portion-controlled diet. CMS-recommended lifestyle counseling: 21 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Portion-Controlled Diet: A 1000-1200 kcal/day portion-controlled diet prescribed for 12 weeks, beginning at week 4. | 0 | 50 | 3 | 50 | 44 | 50 |
| EG003 | 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. CMS-recommended lifestyle counseling: 4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Phentermine 15 MG | 1 | 22 | 1 | 22 | 12 | 22 |
| EG004 | 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. CMS-recommended lifestyle counseling: 4 brief (15 minute) lifestyle counseling visits provided by a physician, nurse practitioner, or registered dietitian. Liraglutide 3.0mg: Liraglutide is a once-daily self-administered, subcutaneous (beneath the skin) injection. Placebo Oral Tablet | 0 | 23 | 0 | 23 | 11 | 23 |
| Bile duct stone | Hepatobiliary disorders | Systematic Assessment |
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| Gastroenteritis | Gastrointestinal disorders | Systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Wound infection | Infections and infestations | Systematic Assessment |
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| Quadriplegic event | Nervous system disorders | Systematic Assessment |
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| Gastroenteritis | Gastrointestinal disorders | Systematic Assessment |
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| Urinary tract infection | Renal and urinary disorders | Systematic Assessment |
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| Depressed mood | Psychiatric disorders | Systematic Assessment |
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| Tonsillopharyngitis | Infections and infestations | Systematic Assessment |
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| Headache | Nervous system disorders | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | Systematic Assessment |
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| Lower back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Knee pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Sinusitis | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Fatigue | General disorders | Systematic Assessment |
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| Injection site irritation | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Gastroesophageal reflux disorder | Gastrointestinal disorders | Systematic Assessment |
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| Vomitting | Gastrointestinal disorders | Systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Musculoskeletal injury | Musculoskeletal and connective tissue disorders | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | Systematic Assessment |
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| Dry mouth | Gastrointestinal disorders | Systematic Assessment |
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| Heart Palpitations | Cardiac disorders | Systematic Assessment |
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| Restlessness | General disorders | Systematic Assessment |
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Not provided
Not provided
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D000662 | Amphetamines |
| D010627 | Phenethylamines |
| D005021 | Ethylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |