ObesityPhase 4NCT03779048
Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment
A Phase 4 study testing Behavioral Treatment and Phentermine 15 MG in people with Obesity, run by University of Pennsylvania at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Obesity
- What is being tested?
- Behavioral Treatment and Phentermine 15 MG
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 147 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Jul 2019to 25 May 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania Center for Weight and Eating Disorders
Philadelphia, Pennsylvania, 19104
About this study
Official title: Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment
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).
Read the 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.
- Conditions
- Obesity
- Being tested
- Behavioral Treatment, Placebo, Phentermine 15 MG
- Keywords
- phentermine, Hypoglycemic agents, Incretins, Hormones, Appetitive Behavior, Appetite Depressants, Anti-Obesity Agents, Weight Loss, Body Weight, Body Weight Changes, Signs and Symptoms
- Medical subject headings
- Obesity, Appetitive Behavior, Anorexia, Weight Loss, Body Weight, Body Weight Changes, Signs and Symptoms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Behavioral TreatmentBehavioural
Also called Lifestyle modification, Behavioral weight loss
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).
PlaceboDrug
Also called Placebo for medication
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
Phentermine 15 MGDrug
Also called Medication
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
| Study group | Role | What they receive |
|---|---|---|
| Phase 2: Behavioral Treatment + Placebo | Active comparator | 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. Receives: Behavioral: Behavioral Treatment; Drug: Placebo |
| Phase 2: Behavioral Treatment + Medication | Active comparator | 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. Receives: Behavioral: Behavioral Treatment; Drug: Phentermine 15 MG |
| Phase 1: 4-week Behavioral Treatment Run-in | Other | 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. Receives: Behavioral: Behavioral Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase 1: Percent Weight Loss
Co-primary outcomes - phase 1
Measured: 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 (Week 0), Based on Percent Weight Loss
Co-primary outcomes - phase 1
Measured: 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 = [(Post-preload Rating - Fasting Rating Before Preload)] / (Energy Content of Preload in kcal) x 100.
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.
Measured: Baseline (week -5)
Phase 1: Baseline Postprandial Change in GLP-1 During a Test Meal
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.
Measured: Baseline
Phase 1: Baseline Gastric Emptying During a Test Meal (Acetaminophen Test)
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.
Measured: Baseline
Phase 2: Percent Weight Loss
Primary outcomes - phase 2 Percent change from randomization in body weight
Measured: Week 0 (randomization) to week 24
Secondary outcomes (14)
Phase 1: Baseline Hunger, as Measured by Visual Analogue Scales (Range 0-100 mm, Higher = More Hunger) During a Test Meal
Secondary predictor variable - phase 1
Hunger was rated before and at 10 min intervals after a test meal for 60 min. Data presented below are the 60-min area under the curve (AUC) for postprandial change in hunger at baseline.(more negative = more sustained reduction in hunger). 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 hunger scale score at time i.
Measured: Baseline
Phase 1: Baseline Relative Reinforcing Value of Food (Computer Task), Number of Food Reinforcer Points Earned
Secondary predictor variable - phase 1
Subjects are allowed to work to earn points from a slot machine task at either of two computer stations, one of which provides points towards obtaining a serving of a preferred high-calorie food, and the other points towards a preferred low-calorie food. Points are earned on a progressive ratio scale that increases at fixed intervals. The primary outcome is the number of reinforcer points (servings) earned for the high energy density food, which is thought to reflect the subject's willingness to allocate time and effort to obtaining desired high-calorie foods. The minimum number of points that can be earned is 0; there is no specified maximum.
Measured: Baseline
Phase 1: Baseline Delay Discounting (Computer Task), Area Under the Curve Representing the Ratio of Immediate Reward Size to Time Delay
Secondary predictor variable - phase 1
Delay discounting is assessed via a computer program in which subjects are offered choices between small, immediate monetary rewards and larger, delayed rewards. The present delay discounting computer task used 7 time delays for $1000.
The outcome is the area under the curve (AUC) representing the ratio of immediate reward size to time delay. AUCs were standardized to fall between 0 and 1 (Myerson et al., 2001) and were calculated for the plot of subjective values vs. delay, with lower values indicating greater discounting. Area under the curve is calculated using the trapezoidal rule to sum the area under each standardized time interval. AUC = Σ i = 0 to i = 1 proportion of max delay*(x(i) + x(i-1))/2) where x is the proportion of the maximum price inflection value at time i.
Measured: Baseline
Phase 1: Baseline Implicit Wanting, Reaction Time on Leeds Food Preference Questionnaire
Secondary predictor variable - phase 1
Implicit wanting is measured by the Leeds Food Preference Questionnaire, a computer-based task using a forced choice paradigm for four categories: High-fat savory, high-fat sweet, low-fat savory, low-fat sweet. Reaction times are transformed to a standardized D-score that is then adjusted for the frequency of selection using a validated algorithm. Scores can range from -100 to 100 with more positive scores indicating a more rapid preference for one category over the other and more negative scores indicating the opposite.
Measured: Baseline
Phase 1: Baseline Fasting Ghrelin
Secondary predictor variable - phase 1
Blood samples were drawn at time 0 (fasting). Active ghrelin. Unit: Picograms per milliliter (pg/mL)
Measured: Baseline
Phase 1: Baseline Fasting Leptin
Secondary predictor variable - phase 1
Unit: Picograms per milliliter (pg/mL) Blood samples were drawn at time 0 (fasting).
Measured: Baseline
Phase 1: Baseline Postprandial Change in Insulin During a Test Meal
Secondary 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. Incremental area under the curve in insulin measured in micro-international units per milliliter (ulU/mL). 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 insulin value in ulU/mL at time i.
Measured: Baseline
Phase 1: Baseline Postprandial Change in Peptide YY During a Test Meal
Secondary 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 PYY in picograms per milliliter (pgmL) at baseline. 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 PYY value in pg/mL at time i.
Measured: Baseline
Phase 2: Weight Loss (kg)
Secondary outcomes - phase 2
Measured: 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
Secondary outcomes - phase 2
Measured: 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
Secondary outcomes - phase 2
Measured: 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
Secondary outcomes - phase 2
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 final analysis uses the 60-minute incremental area under the curve (AUC) for change in appetite suppression from fasting. Higher scores indicate higher sustained appetite suppression. 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 appetite suppression value at time i.
Measured: 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
Secondary outcomes - phase 2
Hunger was rated before and at 10 min intervals after a test meal for 60 min. Data presented below are the 60-min incremental area under the curve (AUC) for postprandial change in hunger at randomization and week 24. More negative scores indicate greater sustained reductions in hunger from fasting. 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 scale score at time i.
Measured: 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
Secondary outcomes - phase 2
Delay discounting is assessed via a computer program in which subjects are offered choices between small, immediate monetary rewards and larger, delayed rewards. The present delay discounting computer task used 7 time delays for $1000.
The outcome is the area under the curve (AUC) representing the ratio of immediate reward size to time delay. AUCs were standardized to fall between 0 and 1 (Myerson et al., 2001) and were calculated for the plot of subjective values vs. delay, with lower values indicating greater discounting. Area under the curve is calculated using the trapezoidal rule to sum the area under each standardized time interval. AUC = Σ i = 0 to i = 1 proportion of max delay*(x(i) + x(i-1))/2) where x is the proportion of the maximum price inflection value at time i.
Measured: Week 0 (randomization) to week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2018
- Study start15 Jul 2019
- Primary completion25 May 2022
- Study completion25 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 147 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jena S Tronieri, PhD, Principal investigator, Perelman School of Medicine at the University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03779048
- Sponsor's protocol ID
- 832077
- Status last verified
- Feb 2025
- First submitted
- 5 Dec 2018
- Last updated
- 11 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Tronieri JS, Ghanbari E, Chevinsky J, LaFata EM, Minnick AM, Rajpal S, Wang SY, Burcaw K, Berkowitz RI, Wadden TA. Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial. Nat Med. 2025 May;31(5):1653-1660. doi: 10.1038/s41591-025-03556-3. Epub 2025 Mar 7.
PubMed 40055520
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment
- ClinicalTrials.gov ID
- NCT03779048
- Acronym / sponsor ID
- 832077
- Conditions
- Obesity
- Keywords
- phentermine, Hypoglycemic agents, Incretins, Hormones, Appetitive Behavior, Appetite Depressants, Anti-Obesity Agents, Weight Loss
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 147 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 15 Jul 2019 (actual)
- Primary completion
- 25 May 2022 (actual)
- Study completion
- 25 May 2022 (actual)
- First posted
- 19 Dec 2018 (actual)
- Results
- Posted 11 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Phase 1 is observational. Phase 2 is a double-blind, placebo-controlled, randomized controlled trial.
| Arm | Type | Receives |
|---|---|---|
| Phase 2: Behavioral Treatment + Placebo | Active comparator | Behavioral: Behavioral Treatment, Drug: PlaceboParticipants 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. |
| Phase 2: Behavioral Treatment + Medication | Active comparator | Behavioral: Behavioral Treatment, Drug: Phentermine 15 MGParticipants 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. |
| Phase 1: 4-week Behavioral Treatment Run-in | Other | Behavioral: Behavioral TreatmentAll 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. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- BMI ≥ 31 kg/m² (or 28 kg/m2 with obesity-related comorbidity)
- Age ≥ 21 years and ≤ 70 years
- Eligible female patients will be:
- Subjects must:
Key exclusion criteria (33 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Behavioral TreatmentAlso: Lifestyle modification, Behavioral weight lossBehavioral 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). | Behavioural | Phase 1: 4-week Behavioral Treatment Run-in, Phase 2: Behavioral Treatment + Medication, Phase 2: Behavioral Treatment + Placebo |
| PlaceboAlso: Placebo for medicationThe study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill. | Drug | Phase 2: Behavioral Treatment + Placebo |
| Phentermine 15 MGAlso: MedicationThe study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill. | Drug | Phase 2: Behavioral Treatment + Medication |
Primary outcome
Phase 1: Percent Weight Loss
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: Week 0 (randomization) to week 24
Primary outcomes - phase 2 Percent change from randomization in body weight
14 secondary outcomes
Phase 1: Baseline Hunger, as Measured by Visual Analogue Scales (Range 0-100 mm, Higher = More Hunger) During a Test Meal
Time frame: Baseline
Phase 1: Baseline Relative Reinforcing Value of Food (Computer Task), Number of Food Reinforcer Points Earned
Time frame: 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
Phase 1: Baseline Implicit Wanting, Reaction Time on Leeds Food Preference Questionnaire
Time frame: Baseline
Phase 1: Baseline Fasting Ghrelin
Time frame: Baseline
Phase 1: Baseline Fasting Leptin
Time frame: Baseline
Phase 1: Baseline Postprandial Change in Insulin During a Test Meal
Time frame: Baseline
Phase 1: Baseline Postprandial Change in Peptide YY During a Test Meal
Time frame: Baseline
Phase 2: Weight Loss (kg)
Time frame: 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
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
Phase 2: Change in Appetite Suppression, as Measured by Visual Analogue Scales (Range 0-100 mm) During a Test Meal
Time frame: 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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40055520Tronieri JS, Ghanbari E, Chevinsky J, LaFata EM, Minnick AM, Rajpal S, Wang SY, Burcaw K, Berkowitz RI, Wadden TA. Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial. Nat Med. 2025 May;31(5):1653-1660. doi: 10.1038/s41591-025-03556-3. Epub 2025 Mar 7.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jena S Tronieri, PhD principal investigator
Perelman School of Medicine at the University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Behavioral Treatment and Phentermine 15 MG in people with Obesity, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 33 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase 1: Percent Weight Loss (time frame: Week -4 (start of BT run-in) to week 0 (randomization)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03779048, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2025.