Adjunct Phentermine + Topiramate After Bariatric Surgery in 12-24 Year Olds

Phase 2

Completed

Conditions: Bariatric Surgery
Young Adult
Obesity, Morbid
Adolescent
Drug Therapy

Interventions: Drug: Placebo for Phentermine
Drug: Phentermine
Drug: Placebo for Immediate Release Topiramate
Drug: Immediate Release Topiramate

Registration Number: NCT04095104

Lead Sponsor: University of Colorado, Denver

Brief Summary: The goal of this pilot study is to establish the feasibility and initial efficacy of the combination of phentermine and topiramate for adolescents and young adults who require additional risk reduction after bariatric surgery. This study will use a randomized, placebo-controlled, double-blinded design to evaluate an adjunctive 12-week intervention of phentermine + topiramate + standard of care vs. placebos + standard of care 6 months after bariatric surgery, among 12 to 24 year olds who don't achieve expected weight loss or who remain severely obese (n=10 total).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Status post sleeve gastrectomy or roux-en-y gastric bypass
At 6 months after bariatric surgery, has not achieved >= 26% decrease in weight from preoperative weight (within 1 week of surgery) OR remains severely obese (>=120% of 95th%ile or BMI >=35kg/m2 for 12-17yo; BMI >=35kg/m2 for 18-24yo)

Exclusion Criteria

Absolute contraindication to phentermine or topiramate (i.e. phentermine:

history of coronary artery disease, stroke, arrhythmia, congestive heart failure, uncontrolled hypertension), hypersensitivity to sympathomimetic amines, current or recent (within 14 days) use of monoamine oxidase inhibitors, glaucoma, or hyperthyroidism; topiramate: hypersensitivity to topiramate, history of nephrolithiasis)

Concomitant use of phenytoin, carbamazepine, or carbonic anhydrase inhibitors (e.g. zonisamide, acetazolamide, or dichlorphenamide)
Use of anti-obesity medication within 6 months of screening
Initiation of a new medication associated with weight loss or gain within 30 days of screening
Type 2 diabetes mellitus
Hypothalamic obesity
Unmanaged (e.g. without medications and/or psychotherapy) clinically significant (determined by a mental health professional using diagnostic instruments and/or clinical interview) depression or anxiety
History of any suicidal behavior within 30 days of screening or any suicidal ideation with either some intent to act or with intent and a specific plan within 30 days of screening
History of schizophrenia
Severe hepatic impairment (ALT >10x upper limit of normal or known synthetic liver dysfunction)
Moderate or severe renal impairment (GFR <30mL/min/1.73m2)
Dosage change to hypertension, dyslipidemia, depression, or anxiety medication <4 weeks prior to study enrollment
Contraception started <7 days prior to study enrollment
Current pregnancy/plans to become pregnant within 16 weeks from study drug start date
Females without a long acting reversible contraceptive (LARC) who do not commit to using 2 forms of birth control

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Drugs	Placebo for Phentermine	Placebo Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration: 4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning + Placebo Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning + Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)
Placebo Drugs	Placebo for Immediate Release Topiramate	Placebo Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration: 4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning + Placebo Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning + Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)
Phentermine & Topiramate	Immediate Release Topiramate	Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration: 4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning + Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning + Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)
Phentermine & Topiramate	Phentermine	Phentermine- Formulation: 8mg scored tablet, Dosage/Frequency/Duration: 4mg x 7d then 8mg x 7d then 12mg x 7d then 16mg x 63d, taken once every morning + Immediate release topiramate- Formulation: 25mg tablet, Dosage/Frequency/Duration: 25mg x 7d then 50mg x 7d then 75mg x 7d then 100mg x 63d then 50mg x 7 days then 25mg x 7d, taken once every morning + Standard of Care (multidisciplinary postoperative bariatric surgery clinic visits)

Primary Outcome Measures

Name	Time	Method
Enrollment Rate	6 months	(Number enrolled divided by number eligible) x 100
Dropout Rate	24 months	Number who do not complete the study divided by number enrolled
Number of Participants Adherent to Study Drugs	12 weeks	Presence of amphetamine in the urine at any study visit
Frequency of Adverse Events	24 months	Unique adverse events documented prior to unblinding. Adverse events were elicited using a standardized checklist during study phone calls and in-person study visits, laboratory monitoring, review of systems, vitals, physical exam, and mood/suicidality assessment using validated instruments at every study visit.

Secondary Outcome Measures

Name	Time	Method
Change in Total Cholesterol (mg/dL)	Baseline and 12 weeks	Total cholesterol at baseline - Total cholesterol at 12 weeks
Change in Triglycerides (mg/dL)	Baseline and 12 weeks	Triglycerides at baseline - Triglycerides at 12 weeks
Change in LDL Cholesterol (mg/dL)	Baseline and 12 weeks	LDL at baseline - LDL at 12 weeks
Change in HDL Cholesterol (mg/dL)	Baseline and 12 weeks	HDL at baseline - HDL at 12 weeks
Change in Alanine Aminotransferase (ALT) (U/L)	Baseline and 12 weeks	ALT at baseline - ALT at 12 weeks
Percent BMI Change	Baseline and 12 weeks	(Baseline BMI - BMI at 12 weeks)/Baseline BMI x 100
Percent Weight Change	Baseline and 12 weeks	(Baseline weight - weight at 12 weeks)/Baseline weight x 100
Change in BMI Percent of the 95th%Ile	Baseline and 12 weeks	(Baseline BMI % of the 95th%ile - BMI % of the 95th%ile at 12 weeks)
Change in Hemoglobin A1c (HbA1c) (%)	Baseline and 12 weeks	HbA1c at baseline - HbA1c at 12 weeks
Change in % Fat Mass	Baseline and 12 weeks	% Fat mass at baseline - %Fat mass at 12 weeks measured by DEXA
Change in Resting Metabolic Rate (RMR)	Baseline and 12 weeks	RMR at baseline - RMR at 12 weeks measured by indirect calorimetry
Change in Heart Rate	Baseline and 12 weeks	(Heart rate at baseline - Heart rate at 12 weeks)
Change in Systolic Blood Pressure	Baseline and 12 weeks	Systolic blood pressure at baseline - Systolic blood pressure at 12 weeks
Change in Diastolic Blood Pressure	Baseline and 12 weeks	Diastolic blood pressure at baseline - Diastolic blood pressure at 12 weeks
Change in Daily Kilocalorie Intake	Baseline and 12 weeks	The average kilocalorie intake of 3 days was calculated each at baseline and 12 weeks. Kilocalories were calculated based on a standardized self-reported log of two weekdays and 1 weekend day.
Change in Hunger	Baseline and 12 weeks	The adolescent/young adult will report subjective hunger before each meal and snack for 24 hours using a visual analogue slider scale (0= no hunger, 100 = most hunger) and this score will be averaged over the 24 hour period.
Change in Satiety	Baseline and 12 weeks	The adolescent/young adult will report subjective satiety 30 minutes after each meal and snack for 24 hours using a visual analogue slider scale (0= no fullness, 100 = most full) and this score will be averaged over the 24 hour period.
Change in Eating in the Absence of Hunger	Baseline and 12 weeks	Validated questionnaire: Eating in the Absence of Hunger-Parent (EAH-P) completed by the parent/guardian about their adolescent/young adult. This measure has 14 items. Each item is on a 5-point Likert scale ranging from 1= "never" to 5= "always". A higher score indicates more eating in the absence of hunger. Total scores (minimum 14 to maximum 70) are calculated by taking the sum of the 14 items at each time point. The mean change in total scores by group are presented.
Change in Cognitive Restraint	Baseline and 12 weeks	The "Three-Factor Eating Questionnaire" will be completed by the adolescent/young adult. This is a 51-item questionnaire that assesses 3 eating behaviors: Cognitive Dietary Restraint, Disinhibited Eating, and Predisposition to hunger. Cognitive restraint was the domain of highest interest for this study and is reported here. Higher scores in each domain indicate more of each of those behaviors. The cognitive restraint domain score is calculated by taking the average of the 21 items in that domain. Each of the 21 items has a score of 0 or 1. MINIMUM mean score for this measure is: 0 and MAXIMUM mean score is 1. MINIMUM total score for this measure is: 0 and MAXIMUM total score is 21 (relevant to the "Full Range" in the data table below)
Change in Total Weight Related Quality of Life- Adolescent/Young Adult Report	Baseline and 12 weeks	"Impact of Weight on Quality of Life-Kids" questionnaire will be completed by the adolescents age \<=19. Total and each of the 4 sub scales (Physical Comfort-6 items, Body Esteem-9 items, Social Life-6 items, and Family Relations-6 items) range from a minimum score of 0 to a maximum of 100. Higher scores indicate higher quality of life.
Change in Total Weight Related Quality of Life- Parent Reported of Adolescent/Young Adult	Baseline and 12 weeks	"Impact of Weight on Quality of Life-Kids Parent Proxy" questionnaire will be completed by the parent of the adolescent/young adult. Total and each of the 4 sub scales (Physical Comfort-6 items, Body Esteem-9 items, Social Life-6 items, and Family Relations-6 items) range from a minimum score of 0 to a maximum of 100. Higher scores indicate higher quality of life.
Change in General Health Related Quality of Life: Total Score PedsQL Instrument - Self Report	Baseline and 12 weeks	PedsQL instrument will be completed by the adolescent/young adult. The CHANGE in total scale score is reported here. The total scale score at each time point ranges from a MIN of 0 to a MAX of 100. Items are rated on a 0-4 scale. Items are reverse scored and linearly transformed to a 0-100 scale, such that 0=100, 1=75, 2=50, 3=25, and 4=0. Scale Scores are calculated as the sum of the items over the number of items answered. Higher scores indicated better health-related quality of life.
Change in Depression	Baseline and 12 weeks	The adolescent/young adult will complete the 20-item Center for Epidemiologic Studies Depression Scale (CES-D). Each item is rated on a 0 to 3 scale (positive items are reverse scored). Minimum score is 0 and maximum is 60. Higher scores indicate more depressive symptoms. Total score is calculated by summing each of the 20 individual items scores.
Participant Satisfaction: Questionnaire	At 12 weeks	The participating family will be asked to complete a satisfaction questionnaire that will assess reasons for participation, experience during study visits, satisfaction with the effect of the study drug, ease of communication with study staff, and study burden. The outcome presented here is the average of the parent and adolescent/young adult dyad's response to the statement: "My overall experience was positive" \[1=Strongly disagree, 5=Strongly agree\]