Short- and Long-term Effects of Once Weekly Semaglutide 2.4 mg on Appetite, Eating Behavior, and Psychosocial Status
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Ad libitum energy intake (kcal) during a buffet lunch meal (4 hrs after standardized breakfast)
研究概览
简要总结
This study will evaluate the effect of semaglutide on eating behavior, appetite (hunger/fullness), and food liking in the long-term, as compared to placebo. All participants will receive lifestyle modification (diet and exercise) counseling, and will be prescribed the FDA-approved weight loss medication, semaglutide, or placebo (an inactive saline solution) for 72 weeks.
详细描述
This trial consists of a single 72-week treatment period during which two studies will be conducted. Study 1 (i.e., long-term treatment trial; weeks 0-60) is a 60-week, single center, double-blinded, randomized controlled, parallel group design trial, and Study 2 (i.e., re-randomized medication withdrawal trial; weeks 60-72) is a separate, 12-week, double-blind, re-randomized medication withdrawal trial.
The long-term treatment trial (Study 1) will randomly assign (in a 3:2 semaglutide:placebo ratio) 120 subjects with a body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 with ≥1 obesity-related co-morbidities, to 60 weeks of: 1) placebo with moderate intensity lifestyle intervention (as used in STEP 1); or 2) semaglutide 2.4 mg with the same lifestyle intervention. All subjects will receive 60 weeks of trial product, which will be up-titrated over 16 weeks in those assigned to semaglutide 2.4 mg. They will complete assessments of energy intake, appetite, food reward, mood, symptoms of disordered eating, and anthropomorphic measurements at baseline (week 0) and weeks 20, 40, and 60.
The primary aim in the initial long-term treatment trial will be to compare the long-term effect of semaglutide 2.4 mg vs placebo on ad libitum energy intake during a lunch meal at weeks 20, 40, and 60. Confirmatory secondary aims will test the effect of semaglutide 2.4 mg at weeks 20, 40 and 60 on subjective appetite ratings (both measured during a standardized breakfast in the lab and as experienced more globally over the past week), explicit food reward, as measured with the Power of Food Scale (24), and implicit food reward, as measured with the Leeds Food Preference Task (25, 26). Measures of food cravings, mood, eating disorder symptoms, and self-report measures of eating behavior will be considered supportive secondary endpoints and will provide additional evidence of the medication's safety and efficacy.
Following the completion of Study 1 at week 60, all subjects who complete a week 60 assessment and remain on drug will be enrolled in Study 2. Semaglutide-treated subjects will be re-randomized (in a 1:4 semaglutide:placebo ratio) to receive semaglutide 2.4 mg or placebo for 12 weeks. All subjects originally assigned to placebo will continue with that medication for an additional 12 weeks. Both researchers and subjects will remain blinded to subjects' original and re-randomized (or continued) treatment assignments. The goal of this re-randomized medication withdrawal period will be to compare the 80% of subjects originally assigned to semaglutide 2.4 mg who receive placebo at week 60 (semaglutide-to-placebo group) to the subjects originally randomized to placebo (continuous-placebo group) on all primary and secondary outcome measures at week 72 (after controlling for Study 1 baseline/week 0 values). All subjects will terminate trial product at cumulative week 72 and will return to clinic for a final safety visit at week 76.
Outcome assessments including ad libitum energy intake, subjective measures of appetite, food reward, eating behavior, mood, and eating disorder symptoms will occur at weeks 0, 20, 40, and 60 of Study 1 and at week 12 (72 weeks from original randomization) of the re-randomized treatment period. Measurements of body weight, waist circumference, blood pressure, pulse, and global, past-week appetite and food cravings (COEQ) also will be collected every 4 weeks throughout both treatment studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blind
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women who report a desire to lose weight
- •Aged 18-70 years
- •Body mass index [BMI] ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with an obesity-related comorbidity (e.g., treated or untreated hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease)
- •Eligible female patients will be:
- •non-pregnant, evidenced by a negative urine 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
- •Subjects must
- •Plan to remain in the Philadelphia area for the next 1.5 years.
- •Ability to provide informed consent before any trial-related activities.
排除标准
- •A diagnosis of type I or II diabetes
- •Hemoglobin A1c (HbA1c) > 6.5%
- •Uncontrolled hypertension (blood pressure ≥ 160/100 mm Hg)
- •Clinically significant hepatic (i.e., liver fibrosis, cirrhosis or confirmed NASH) or renal disease
- •Uncontrolled thyroid disease
- •Experienced a cardiovascular event (e.g., stroke, myocardial infarction) in the last 6 months, congestive heart failure, or heart block greater than first degree
- •A history of acute pancreatitis in the last 6 months
- •Any history of chronic pancreatitis
- •A history of malignancy (other than non-melanoma skin cancer) within the last 5 years
- •A personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2
- •A self-reported change in body weight >5kg (11 lbs) within 90 days before screening
- •Used within the last 6 months medications known to produce weight loss/gain (e.g., medications approved for weight loss, oral steroids, antipsychotic medications) or any GLP-1 receptor agonist.
- •Known or suspected allergy or hypersensitivity to trial medication(s), excipients, or related products
- •The receipt of any investigational drug within 6 months prior to this trial
- •Applicants with current severe major depressive disorder (BDI-II score ≥ 29 or Patient Health Questionnaire-9 [PHQ-9] score > 15) or severe anxiety disorder
- •Applicants with current, active suicidal ideation, and/or a suicide attempt within the past year (such individuals will be referred for psychiatric treatment if they have not previously received it).
- •Any severity of psychotic or bipolar disorder
- •Bulimia nervosa diagnosis within the past 5 years
- •Self-reported alcohol or substance abuse within the past 6 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
- •History of (or plans to receive in the next 1.5 years) bariatric surgery or a weight loss device. (However, the following will be allowed: liposuction or abdominoplasty > 1 year before screening, laparoscopic banding if removed > 1 year before screening, intragastric balloon or aspire assist if removed > 1 year before screening.)
- •Inability to walk 5 blocks or more (comfortably) or engage in another form of aerobic activity.
- •Women who are nursing, pregnant, or planning to become pregnant in the next 1.5 years or are not using adequate contraceptive measures
- •Previous participation in this trial (e.g., randomized but failed to participate)
- •Changes to any chronic medication (type or dosage) within the past 3 months.
- •Food allergy or dietary preference that would prevent the individual from consuming the standard breakfast or ad libitum lunch.
- •1. To be eligible to participate in the re-randomized treatment period from weeks 60 to 72, subjects must also:
- •complete a week 60 assessment
- •be classified as "on drug" as at the week 60 assessment and report taking at least one dose of trial product within the past 2 weeks
结局指标
主要结局
Ad libitum energy intake (kcal) during a buffet lunch meal (4 hrs after standardized breakfast)
时间窗: S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline
Primary outcome
Study 1 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)
时间窗: S1: Change from baseline to weeks 20, 40, and 60
Primary outcome (Study 1)
Study 2 Ad Libitum Energy Intake (kcal) During a Buffet Lunch Meal (4 Hrs After Standardized Breakfast)
时间窗: S2: Endpoint comparison at week 72
Primary outcome (Study 2)
次要结局
- Laboratory-based appetite measured as a composite of visual analogue scale ratings (hunger, fullness, satiety, prospective consumption) when fasting and after eating (area under the curve). This is a single outcome calculated by combining the VAS ratings(S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline)
- Global subjective appetite (e.g., hunger, fullness, food preoccupation) over the past week measured using the Control of Eating Questionnaire (COEQ)(S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline)
- Explicit responsiveness to the food environment measured by the summary score of the Power of Food Scale (15-item version)(S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline)
- Implicit food wanting of high-fat, savory foods measured using the Leeds Food Preference Task(S1: Change from baseline to weeks 20, 40, and 60; S2: Week 72 endpoint controlling for S1 baseline)
- Study 1 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) After Eating (Area Under the Curve)(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)(S1: Change from baseline to weeks 20, 40, and 60)
- Study 1 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task(S1: Change from baseline to weeks 20, 40, and 60)
- Study 2 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) When Fasting(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Laboratory-based Appetite Measured as a Composite of Visual Analogue Scale Ratings (Hunger, Fullness, Satiety, Prospective Consumption) After Eating (Area Under the Curve)(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Past-week Hunger as Measured Using the Control of Eating Questionnaire (COEQ)(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Past-week Fullness After Meals as Measured Using the Control of Eating Questionnaire (COEQ)(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Past-week Food Preoccupation as Measured Using the Control of Eating Questionnaire (COEQ)(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Explicit Responsiveness to the Food Environment (Power of Food Scale 15-item Version)(S2: Week 72 endpoint controlling for S1 baseline)
- Study 2 Implicit Food Wanting of High-fat, Savory Foods Measured Using the Leeds Food Preference Task(S2: Week 72 endpoint controlling for S1 baseline)