- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03779048
Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment
Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
The primary endpoint of phase 2 is change in body weight (i.e., % reduction in initial weight), as measured from randomization to week 24, among suboptimal early responders assigned to BT+P vs. BT+M. A randomized sample size of 50 non-responders (25 per group), assuming a 20% attrition rate, will give us 81.5% power to detect between-treatment group differences at week 24 of 4.5% (effect size: d = 0.82).
Secondary endpoints of phase 2 will include change in body weight in kg from randomization to week 24, as well as the portion of suboptimal early responders who achieve a post-randomization loss of ≥ 5% and ≥ 10% of initial body weight. We will also examine differences between suboptimal early responders treated with BT+M vs. BT+P in changes in hunger, satiety, the reinforcing efficacy of food, and impulsivity between randomization and week 24. A comparison will also be made in percent weight loss from randomization to week 24 between suboptimal early responders treated with BT+M and early responders treated with BT alone.
If you are interested in participating in this study, information and a link to contact the research team can be found here: https://clinicalresearch.itmat.upenn.edu/3XOX/ or you can call us at the numbers listed below.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Pennsylvania
-
Philadelphia, Pennsylvania, United States, 19104
- University of Pennsylvania Center for Weight and Eating Disorders
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Behavioral Treatment + Placebo
All participants will complete an initial 4-week behavioral treatment (BT) run-in. 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. |
Behavioral treatment (BT) for weight loss includes diet and physical activity recommendations and behavior therapy strategies.
All participants will complete an initial 4-week BT run-in, delivered in individual, 20-30 minute weekly sessions.
After the end of the run-in, participants will be offered an additional 24 weeks of 20-30 minute individual BT sessions, occurring weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits).
Other Names:
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
Other Names:
|
Active Comparator: Behavioral Treatment + Medication
All participants will complete an initial 4-week behavioral treatment (BT) run-in. 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. |
Behavioral treatment (BT) for weight loss includes diet and physical activity recommendations and behavior therapy strategies.
All participants will complete an initial 4-week BT run-in, delivered in individual, 20-30 minute weekly sessions.
After the end of the run-in, participants will be offered an additional 24 weeks of 20-30 minute individual BT sessions, occurring weekly for the first 12 weeks and every other week for the last 12 weeks (total of 18 visits).
Other Names:
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Percent weight loss
Time Frame: Week -4 (start of BT run-in) to week 0 (randomization)
|
Co-primary outcomes - phase 1
|
Week -4 (start of BT run-in) to week 0 (randomization)
|
Phase 1: Number of participants who are categorized as early non-responders at randomization, based on percent weight loss
Time Frame: Week -4 (start of BT run-in) to week 0 (randomization)
|
Co-primary outcomes - phase 1
|
Week -4 (start of BT run-in) to week 0 (randomization)
|
Phase 1: Baseline satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.
Time Frame: Baseline (week -5)
|
Primary predictor variable - phase 1
|
Baseline (week -5)
|
Phase 1: Baseline postprandial change in GLP-1 during a test meal
Time Frame: Baseline
|
Primary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline gastric emptying during a test meal (acetaminophen test)
Time Frame: Baseline
|
Primary predictor variable - phase 1
|
Baseline
|
Phase 2: Percent weight loss
Time Frame: Week 0 (randomization) to week 24
|
Primary outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Baseline hunger, as measured by visual analogue scales (range 0-100 mm, higher = more hunger) during a test meal
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline relative reinforcing value of food (computer task), number of food reinforcer points earned
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline delay discounting (computer task), area under the curve representing the ratio of immediate reward size to time delay
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline implicit wanting of food, reaction time on Leeds Food Preference Questionnaire
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline fasting ghrelin
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline fasting leptin
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline postprandial change in insulin during a test meal
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline postprandial change in peptide YY during a test meal
Time Frame: Baseline
|
Secondary predictor variable - phase 1
|
Baseline
|
Phase 2: Weight loss (kg)
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
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
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
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
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in satiety, as measured by visual analogue scales (range 0-100 mm) during a test meal; satiety quotient = [(fasting rating before preload - 60 min post-preload rating)] / (energy content of preload) x 100.
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
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
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in relative reinforcing value of food (computer task), number of food reinforcer points earned
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
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
Time Frame: Week 0 (randomization) to week 24
|
Secondary outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Baseline eating behavior as measured by The Eating Inventory (EI); Dietary restraint subscale (scored 0-21 higher=more restraint), Disinhibition sub scale (scored 0-16 higher=more disinhibition), Hunger sub scale (scored 0-14 higher=more hunger)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm, higher=greater amount or frequency)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline reinforcing value of food as measured by the Power of Food Scale (PFS; range 1-5, higher=greater power of food)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline sensitivity to reward as measured by the Behavioral Inhibition/Activation Scale (BIS/BAS) (BIS subscale range 7-28, higher = greater inhibition; BAS reward responsiveness sub scale range 5-20, higher=greater reward responsiveness, etc)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline impulsivity as measured by The Barratt Impulsiveness Scale (BIS-15, range 15-60, higher= more impulsiveness)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline binge eating as measured by The Questionnaire on Eating and Weight Patterns (QEWP-5); Measure categorizes participants based on whether they may meet diagnostic criteria for binge eating disorder
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline craving frequency as measured by the Food Craving Q Trait - Reduced
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline emotional eating as measured by the Dutch Eating Behaviour Questionnaire (DEBQ)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline perceived barriers to healthy eating and physical activity (Scale by Welsh et al., 2012)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline Weight Efficacy Life-Style Questionnaire (WEL)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline SCI Exercise Self Efficacy Scale (ESES)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Randomization Ball and Crawford Social Support Scale
Time Frame: Randomization (week 0)
|
Exploratory predictor variable - phase 1
|
Randomization (week 0)
|
Phase 1: Baseline food addiction using the Yale Food Addiction Scale (YFAS)
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: The reinforcing efficacy of high- and low-calorie food
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline sleep hours survey
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline Perceived Stress Scale
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline anxiety as measured by the GAD-7
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 1: Baseline general mindfulness and acceptance as measured using the Philadelphia Mindfulness Scale
Time Frame: Baseline
|
Exploratory predictor variable - phase 1
|
Baseline
|
Phase 2: Change in blood pressure
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in pulse
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in waist circumference
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in triglycerides
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in HDL and LDL cholesterol
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in fasting blood sugar
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm)
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in quality of life as measured by the Impact of Weight on Quality of Life (IWQOL)
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Phase 2: Change in physical activity using the Paffenbarger Physical Activity Questionnaire
Time Frame: Week 0 (randomization) to week 24
|
Exploratory outcomes - phase 2
|
Week 0 (randomization) to week 24
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Jena S Tronieri, PhD, Perelman School of Medicine at the University of Pennsylvania
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Body Weight
- Body Weight Changes
- Weight Loss
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Appetite Depressants
- Anti-Obesity Agents
- Central Nervous System Stimulants
- Sympathomimetics
- Phentermine
Other Study ID Numbers
- 832077
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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