Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 147
- 试验地点
- 1
- 主要终点
- Phase 1: Percent Weight Loss
研究概览
简要总结
This is a two-phase study. Phase 1 will evaluate obesity-related behavioral and biological characteristics as potential predictors of response to behavioral treatment (BT) for weight loss. Phase 2 is a double-blind, placebo-controlled, RCT to test whether adding weight loss medication to BT improves 24-week weight loss, as compared to BT with placebo, in subjects identified as having suboptimal early weight loss after 4 weeks of individual behavioral weight control. All participants, regardless of their early weight loss, will receive the same BT program of diet, physical activity, and behavior therapy for weight loss for an additional 24 weeks (28 total weeks of treatment).
详细描述
Subjects will be a total of 150 adults, aged 21-70 years, with a body mass index (BMI) of 31 kg/m2 or above (28 kg/m2 with an obesity-related comorbidity). In phase 1, eligible subjects will complete questionnaires and an in-person baseline assessment of obesity-related behavioral characteristics (satiety, hunger, the relative reinforcing value of food [RRVfood], and impulsivity [delay discounting]), neuropeptides, and gastric emptying. After this baseline assessment, participants will begin an initial 4-week behavioral treatment (BT) "run-in" delivered individually in 20-30 minute weekly sessions (delivered virtually).
The primary goal of phase 1 will be to evaluate baseline satiety, postprandial change in GLP-1, and gastric emptying as predictors of percent weight loss after 4 weeks of BT. We will also examine whether these variables predict categorization as a suboptimal early responder to BT (e.g., <2.0% loss; co-primary outcome).
Secondary endpoints of phase 1 are percent weight loss from the start of the BT run-in (week -4) to randomization (week 0) and categorization as a suboptimal early responder, as predicted by additional behavioral characteristics (hunger as measured by VAS ratings, RRVfood as measured using a computer task, and impulsivity as measured using a delay discounting computer task) and neuropeptides (higher fasting ghrelin, lower fasting leptin, and lower postprandial changes in insulin and PYY).
In phase 2, suboptimal early responders (based on weight loss during the BT run-in) will be randomly assigned to 24 weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg). Both treatment groups will continue to attend 20-30 minute individual BT sessions (delivered virtually), weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits). Both treatment groups will also take once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period. Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
The assessments administered at baseline - questionnaires, including behavioral testing, blood draws, and measurements of body weight - will be repeated at randomization (week 0) and at week 24.
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
- 21 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •BMI ≥ 31 kg/m² (or 28 kg/m2 with obesity-related comorbidity)
- •Age ≥ 21 years and ≤ 70 years
- •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. Acceptable methods of birth control are: hormonal contraceptives; double barrier method (condom with spermicide or diaphragm with spermicide); intrauterine device; surgical sterility; abstinence; and/or postmenopausal status (defined as at least 2 years without menses).
- •Subjects must:
- •have a primary care provider (PCP) who is responsible for providing routine care
- •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 9 months or more
排除标准
- •Pregnant or nursing, or plans to become pregnant in the next 9 months.
- •Uncontrolled hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg)
- •Type 1 diabetes
- •Type 2 diabetes
- •A fasting blood glucose > 126 mg/dL (on second assessment after first elevated value)
- •History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, or heart block greater than first degree
- •Clinically significant hepatic or renal disease
- •Hyperthyroidism
- •Other thyroid disease, not controlled
- •History of malignancy (except for non-melanoma skin cancer) in past 5 years
- •Narrow angle glaucoma
- •Presence or history of marked agitation
- •Current severe major depressive episode (BDI-II score ≥ 29), current active suicidal ideation, or history of suicide attempts within the past 5 years.
- •Any severity of thought or bipolar disorder, or bulimia nervosa.
- •Psychiatric hospitalization within the past 6 months
- •Self-reported alcohol or substance abuse within the past 6 months, including at-risk drinking (current consumption of ≥ 14 alcoholic drinks per week)
- •Past year history of drug abuse
- •Use in the past 2 weeks of monoamine oxidase inhibitors
- •Current use of serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g. venlafaxine, duloxetine, desvenlafaxine, milnacipran, levomilnacipran).
- •Use in past 6 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 ≥ 5% of initial body weight within the past 6 months
- •History of (or plans for) bariatric surgery (e.g., roux en y gastric bypass, sleeve gastrectomy, gastric banding), endoscopic intragastric balloon, or aspire assist.
- •Inability to walk 5 blocks comfortably or engage in some other form of aerobic activity (e.g., swimming)
- •Known or suspected allergy to sympathomimetic amines or related products
- •The receipt of any investigational drug within 6 months prior to this trial
- •Previous participation in this trial (e.g., randomized and failed to participate)
- •Changes to any chronic medication (type or dosage) within the past 3 months.
- •Any serious or unstable medical or psychological condition that, in the opinion of the investigator, would compromise the patient's safety or successful participation in the study
- •Other Therapy: Subjects will be expected to use medications (prescribed by their PCP) to control traditional cardiometabolic risk factors (e.g., hypertension, hypercholesterolemia, etc) and other co-morbid conditions, with the exception of medications listed above under "exclusions." In all cases, the subjects' PCP will be asked at the study's outset to keep medication does constant throughout the study, whenever possible. Subjects will be expected to have been on their medication regimen (including the dose) for 3 months prior to beginning the BT program.
- •To be eligible to participate in the randomized phase of the trial, subjects must also:
- •Complete at least 3 out of 4 treatment sessions during the 4-week BT run-in and attend a randomization visit. Attending an in-person makeup session within one week of a missed visit will count as having attended the run-in visit.
- •Lose < 2.0% of initial weight during the 4-week BT run-in.
- •Early BT responders who lose>=2% during the BT run-in will be offered the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
研究组 & 干预措施
Phase 2: Behavioral Treatment + Placebo
Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
干预措施: Behavioral Treatment (Behavioral)
Phase 2: Behavioral Treatment + Placebo
Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
干预措施: Placebo (Drug)
Phase 2: Behavioral Treatment + Medication
Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
干预措施: Behavioral Treatment (Behavioral)
Phase 2: Behavioral Treatment + Medication
Participants with suboptimal early weight loss in the BT run-in will then be randomly assigned to 24 additional weeks of: 1) BT plus placebo (BT+P); or 2) BT plus medication (BT+M; phentermine 15.0 mg) in a double-blinded fashion. Both treatment groups will continue to attend individual BT sessions and will take a once daily study medication (placebo or phentermine 15.0 mg) for the duration of the intervention period.
Early BT responders identified during the run-in will receive the same 24-week BT program, but will not receive study medication or be included in the randomized trial.
干预措施: Phentermine 15 MG (Drug)
Phase 1: 4-week Behavioral Treatment Run-in
All enrolled participants will complete an initial 4-week behavioral treatment (BT) run-in. This run-in will be used to identify early non-responders to BT, defined by a weight loss <2% of initial weight after 4 weeks of BT. Early responders are those who lose >=2%.
Only early non-responders will then be enrolled in the randomized trial.
干预措施: Behavioral Treatment (Behavioral)
结局指标
主要结局
Phase 1: Percent Weight Loss
时间窗: Week -4 (start of BT run-in) to week 0 (randomization)
Co-primary outcomes - phase 1
Phase 1: Number of Participants Who Are Categorized as Early Non-responders at Randomization (Week 0), Based on Percent Weight Loss
时间窗: Week -4 (start of BT run-in) to week 0 (randomization)
Co-primary outcomes - phase 1
Phase 1: Baseline Satiety, as Measured by Visual Analogue Scales (Range 0-100 mm) During a Test Meal; Satiety Quotient = [(Post-preload Rating - Fasting Rating Before Preload)] / (Energy Content of Preload in kcal) x 100.
时间窗: Baseline (week -5)
Primary predictor variable - phase 1 Appetite suppression was first calculated as the average of 100 mm VAS items: hunger (reverse score), satisfaction, fullness, and prospective consumption (reverse score), such that higher scores indicate more appetite suppression (less appetite) for each test meal rating (fasting, then every 10m for 60m). The satiety quotient was then calculated for each post-preload rating using the above formula (see measure title). More positive scores show increased satiety (more appetite suppression). The final analysis uses the 60-minute area under the curve (AUC) for the satiety quotient to predict phase 1 weight loss outcomes. Area under the curve is calculated using the trapezoidal rule to sum the area under each 10-minute interval. AUC = Σ i = 0 to i = 60 10min\*(x(i) + x(i-1))/2) where x is the satiety quotient value at time i. Higher scores indicate higher sustained satiety.
Phase 1: Baseline Postprandial Change in GLP-1 During a Test Meal
时间窗: Baseline
Primary predictor variable - phase 1. Blood samples were drawn at time 0 (fasting) and 30- and 60-min postprandial samples after consumption of a test meal. Value presented below is the 60-minute incremental area under the curve (AUC) for GLP-1 in picomoles (pM). Area under the curve is calculated using the trapezoidal rule to sum the area under each 0.5-hour interval. AUC = Σ i = 0 to i = 1 0.5hr\*(x(i) + x(i-1))/2) where x is the GLP-1 value in pM at time i.
Phase 1: Baseline Gastric Emptying During a Test Meal (Acetaminophen Test)
时间窗: Baseline
Primary predictor variable - phase 1 Gastric emptying was measured as the 60-minute area under the curve (AUC) for acetaminophen in micrograms per milliliter (ug/mL). Blood samples were obtained at time 0 (fasting/no acetaminophen - confirmatory) and 30 and 60-min after ingestion. Because acetaminophen is minimally absorbed by the stomach but quickly enters the bloodstream in the small intestine, gastric emptying is considered to be the primary factor influencing its appearance in the blood. Area under the curve is calculated using the trapezoidal rule to sum the area under each 0.5-hour interval. AUC = Σ i = 0 to i = 1 0.5hr\*(x(i) + x(i-1))/2) where x is the acetaminophen value in ug/mL at time i.
Phase 2: Percent Weight Loss
时间窗: Week 0 (randomization) to week 24
Primary outcomes - phase 2 Percent change from randomization in body weight
次要结局
- Phase 1: Baseline Postprandial Change in Insulin During a Test Meal(Baseline)
- Phase 1: Baseline Hunger, as Measured by Visual Analogue Scales (Range 0-100 mm, Higher = More Hunger) During a Test Meal(Baseline)
- Phase 1: Baseline Relative Reinforcing Value of Food (Computer Task), Number of Food Reinforcer Points Earned(Baseline)
- Phase 1: Baseline Delay Discounting (Computer Task), Area Under the Curve Representing the Ratio of Immediate Reward Size to Time Delay(Baseline)
- Phase 1: Baseline Implicit Wanting, Reaction Time on Leeds Food Preference Questionnaire(Baseline)
- Phase 1: Baseline Fasting Leptin(Baseline)
- Phase 1: Baseline Fasting Ghrelin(Baseline)
- Phase 1: Baseline Postprandial Change in Peptide YY During a Test Meal(Baseline)
- Phase 2: Weight Loss (kg)(Week 0 (randomization) to week 24)
- Phase 2: Number of Participants With a Weight Loss of 5% or Greater of Randomization Body Weight at Week 24(Week 0 (randomization) to week 24)
- Phase 2: Number of Participants With a Weight Loss of 10% or Greater of Randomization Body Weight at Week 24(Week 0 (randomization) to week 24)
- Phase 2: Change in Appetite Suppression, as Measured by Visual Analogue Scales (Range 0-100 mm) During a Test Meal(Week 0 (randomization) to week 24)
- Phase 2: Change in Hunger, as Measured by Visual Analogue Scales (Range 0-100 mm, Higher=More Hunger) During a Test Meal(Week 0 (randomization) to week 24)
- Phase 2: Change in Delay Discounting (Computer Task), Area Under the Curve Representing the Ratio of Immediate Reward Size to Time Delay(Week 0 (randomization) to week 24)