Use of Medication to Improve Weight Loss in Suboptimal Early Responders to Behavioral Treatment

Obesity Clinical Trial

Official title:

Use of Pharmacotherapy to Improve Weight Loss in Early Non-responders to Behavioral Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03779048
• Other study ID #: 832077
• Status: Completed
• Phase: Phase 4
• Start date: July 15, 2019
• Est. completion date: May 25, 2022

Study information

• Verified date: September 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 147
• Est. completion date: May 25, 2022
• Est. primary completion date: May 25, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

Inclusion Criteria:

1. BMI = 31 kg/m² (or 28 kg/m2 with obesity-related comorbidity)

2. Age = 21 years and = 70 years

3. 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).

4. 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:

1. Pregnant or nursing, or plans to become pregnant in the next 9 months.

2. Uncontrolled hypertension (systolic blood pressure = 140 mm Hg or diastolic blood pressure = 90 mm Hg)

3. Type 1 diabetes

4. Type 2 diabetes

5. A fasting blood glucose > 126 mg/dL (on second assessment after first elevated value)

6. History of cardiovascular disease (e.g., coronary artery disease, stroke, arrhythmias, congestive heart failure, or heart block greater than first degree

7. Clinically significant hepatic or renal disease

8. Hyperthyroidism

9. Other thyroid disease, not controlled

10. History of malignancy (except for non-melanoma skin cancer) in past 5 years

11. Narrow angle glaucoma

12. Presence or history of marked agitation

13. Current severe major depressive episode (BDI-II score = 29), current active suicidal ideation, or history of suicide attempts within the past 5 years.

14. Any severity of thought or bipolar disorder, or bulimia nervosa.

15. Psychiatric hospitalization within the past 6 months

16. Self-reported alcohol or substance abuse within the past 6 months, including at-risk drinking (current consumption of = 14 alcoholic drinks per week)

17. Past year history of drug abuse

18. Use in the past 2 weeks of monoamine oxidase inhibitors

19. Current use of serotonin-norepinephrine reuptake inhibitors (SNRIs; e.g. venlafaxine, duloxetine, desvenlafaxine, milnacipran, levomilnacipran).

20. 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)

21. Loss of = 5% of initial body weight within the past 6 months

22. History of (or plans for) bariatric surgery (e.g., roux en y gastric bypass, sleeve gastrectomy, gastric banding), endoscopic intragastric balloon, or aspire assist.

23. Inability to walk 5 blocks comfortably or engage in some other form of aerobic activity (e.g., swimming)

24. Known or suspected allergy to sympathomimetic amines or related products

25. The receipt of any investigational drug within 6 months prior to this trial

26. Previous participation in this trial (e.g., randomized and failed to participate)

27. Changes to any chronic medication (type or dosage) within the past 3 months.

28. 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:

1. 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.

2. 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.

Related Conditions & MeSH terms

• Obesity
• Weight Loss

Intervention

Behavioral:
• Behavioral Treatment
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).

Drug:
• Placebo
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.
• Phentermine 15 MG
The study medication (placebo or phentermine 15.0 mg) is a once-daily self-administered pill.

Locations

Country	Name	City	State
United States	University of Pennsylvania Center for Weight and Eating Disorders	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
University of Pennsylvania	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	Exploratory predictor variable - phase 1	Baseline
Other	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)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline reinforcing value of food as measured by the Power of Food Scale (PFS; range 1-5, higher=greater power of food)	Exploratory predictor variable - phase 1	Baseline
Other	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)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline impulsivity as measured by The Barratt Impulsiveness Scale (BIS-15, range 15-60, higher= more impulsiveness)	Exploratory predictor variable - phase 1	Baseline
Other	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	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline craving frequency as measured by the Food Craving Q Trait - Reduced	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline emotional eating as measured by the Dutch Eating Behaviour Questionnaire (DEBQ)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline perceived barriers to healthy eating and physical activity (Scale by Welsh et al., 2012)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline Weight Efficacy Life-Style Questionnaire (WEL)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline SCI Exercise Self Efficacy Scale (ESES)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Randomization Ball and Crawford Social Support Scale	Exploratory predictor variable - phase 1	Randomization (week 0)
Other	Phase 1: Baseline food addiction using the Yale Food Addiction Scale (YFAS)	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: The reinforcing efficacy of high- and low-calorie food	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline sleep hours survey	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline Perceived Stress Scale	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline anxiety as measured by the GAD-7	Exploratory predictor variable - phase 1	Baseline
Other	Phase 1: Baseline general mindfulness and acceptance as measured using the Philadelphia Mindfulness Scale	Exploratory predictor variable - phase 1	Baseline
Other	Phase 2: Change in blood pressure	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in pulse	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in waist circumference	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in triglycerides	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in HDL and LDL cholesterol	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in fasting blood sugar	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in appetite ratings (ratings of appetite during the past week using visual analogue scales, scored 0-100 mm)	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in quality of life as measured by the Impact of Weight on Quality of Life (IWQOL)	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in depressive symptoms as measured by the Patient Health Questionnaire (PHQ-9)	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Other	Phase 2: Change in physical activity using the Paffenbarger Physical Activity Questionnaire	Exploratory outcomes - phase 2	Week 0 (randomization) to week 24
Primary	Phase 1: Percent weight loss	Co-primary outcomes - phase 1	Week -4 (start of BT run-in) to week 0 (randomization)
Primary	Phase 1: Number of participants who are categorized as early non-responders at randomization, based on percent weight loss	Co-primary outcomes - phase 1	Week -4 (start of BT run-in) to week 0 (randomization)
Primary	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.	Primary predictor variable - phase 1	Baseline (week -5)
Primary	Phase 1: Baseline postprandial change in GLP-1 during a test meal	Primary predictor variable - phase 1	Baseline
Primary	Phase 1: Baseline gastric emptying during a test meal (acetaminophen test)	Primary predictor variable - phase 1	Baseline
Primary	Phase 2: Percent weight loss	Primary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	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	Baseline
Secondary	Phase 1: Baseline relative reinforcing value of food (computer task), number of food reinforcer points earned	Secondary predictor variable - phase 1	Baseline
Secondary	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	Baseline
Secondary	Phase 1: Baseline implicit wanting of food, reaction time on Leeds Food Preference Questionnaire	Secondary predictor variable - phase 1	Baseline
Secondary	Phase 1: Baseline fasting ghrelin	Secondary predictor variable - phase 1	Baseline
Secondary	Phase 1: Baseline fasting leptin	Secondary predictor variable - phase 1	Baseline
Secondary	Phase 1: Baseline postprandial change in insulin during a test meal	Secondary predictor variable - phase 1	Baseline
Secondary	Phase 1: Baseline postprandial change in peptide YY during a test meal	Secondary predictor variable - phase 1	Baseline
Secondary	Phase 2: Weight loss (kg)	Secondary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	Phase 2: Number of participants with a weight loss of 5% or greater of randomization body weight at week 24	Secondary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	Phase 2: Number of participants with a weight loss of 10% or greater of randomization body weight at week 24	Secondary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	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.	Secondary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	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	Week 0 (randomization) to week 24
Secondary	Phase 2: Change in relative reinforcing value of food (computer task), number of food reinforcer points earned	Secondary outcomes - phase 2	Week 0 (randomization) to week 24
Secondary	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	Week 0 (randomization) to week 24