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

University of Colorado Denver (CU Denver)

Status and phase: Completed; Phase 2

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

Treatments: Drug: Placebo for Immediate Release Topiramate; Drug: Placebo for Phentermine; Drug: Immediate Release Topiramate; Drug: Phentermine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT04095104

5P30DK048520-24 (U.S. NIH Grant/Contract)

18-2793

Details and patient eligibility

About

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).

Enrollment: 13 patients

Sex: All

Ages: 12 to 24 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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13 participants in 2 patient groups, including a placebo group

Phentermine & Topiramate

Experimental group

Description:

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)

Treatment:

Drug: Phentermine

Drug: Immediate Release Topiramate

Placebo Drugs

Placebo Comparator group

Description:

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)

Treatment:

Drug: Placebo for Phentermine

Drug: Placebo for Immediate Release Topiramate