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Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

Primary Purpose

Pediatric Obesity

Status
Recruiting
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Phentermine/Topiramate (Qsymia)
Placebo
Sponsored by
University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pediatric Obesity

Eligibility Criteria

12 Years - 20 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ages 12 to </= 20 years at study entry
  • Obesity (BMI >/= the 95th percentile for age and sex)
  • HgbA1c >/= 6.5% at type 2 diabetes diagnosis
  • Negative diabetes auto-antibodies
  • English-speaking and Spanish speaking
  • For participants of child-bearing potential: when sexually active, agreement to use two forms of highly effective contraception (oral contraceptive pill, IUD, implant, and/or condoms) during study participation

Exclusion Criteria:

  • Pregnancy or lactation
  • Newly-initiated or change in dose of weight altering medication within past 6 months, including SGLT-2 inhibitors and DPP-IV inhibitors, liraglutide 1.8 mg and exenatide ER.
  • Current or recent (< six months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination PHN/TPM, semaglutide, and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion)
  • Current use of sulfonylureas
  • Previous metabolic/bariatric surgery
  • Current use of a stimulant medication
  • History of glaucoma
  • Current or recent (< 14 days) use of monoamine oxidase inhibitor or carbonic anhydrase inhibitors
  • Known hypersensitivity to sympathomimetic amines
  • Any history of treatment with growth hormone
  • any history of bulimia nervosa
  • Major psychiatric disorder as determined by the local medical monitor
  • Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression or PHQ-9 score of >/= 15
  • Any history of active suicide attempt, a "yes" answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the C-SSR, or a "yes" to answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS
  • History of suicidal ideation or self-harm within the previous 30 days or a "yes" answer to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS and the ideation or behavior occurred within the past month.
  • Current pregnancy or plans to become pregnant during study participation
  • Current tobacco use
  • ALT or AST >/= 3 times the upper limit of normal
  • Moderate (Child-Pugh score 7-9) or severe (Child-Pugh score 10-15)
  • Bicarbonate <18 mmol/L
  • Moderate (creatinine clearance [CrCl] greater than or equal to 30 and less than 50 mL/min) or severe (CrCl less than 30 mL/min) renal impairment

  • Any history of seizures

    • BP for ages 13 and older of > 130/80 on 3 separate measurements and for age 12 > 95th percentile on 3 separate measurements

  • HR ≥120 bpm on 3 separate measurements
  • History of structural heart defect or clinically significant arrhythmia
  • Diagnosed monogenic obesity
  • Any history of cholelithiasis
  • Any history of nephrolithiasis
  • Clinically diagnosed hyperthyroidism
  • Untreated thyroid disorder or TSH below the lower laboratory limit of normal
  • Any disorder, unwillingness, or inability, not covered by any other exclusion criteria, which in the investigator's opinion may put the participant at risk

Sites / Locations

  • University of MinnesotaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo-Controlled Period

Open Label Extension

Arm Description

Participants in this phase of the study will be randomized 1:1 to receive either phentermine/topiramate or placebo.

Participants in this phase of the study will receive open label phentermine/topiramate.

Outcomes

Primary Outcome Measures

Change in body mass index
The percent change in body mass index (BMI) from Baseline to Month 6 will be calculated. BMI is defined as a person's weight in kilograms divided by the square of height in meters.

Secondary Outcome Measures

Full Information

First Posted
May 5, 2021
Last Updated
October 2, 2023
Sponsor
University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT04881799
Brief Title
Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity
Official Title
Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 7, 2022 (Actual)
Primary Completion Date
August 1, 2025 (Anticipated)
Study Completion Date
August 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Minnesota

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
As the prevalence of obesity rises in the U.S., so does the incidence of pediatric type 2 diabetes (T2D), which is associated with more aggressive disease progression than in adults. From 2002-2012, the incidence of T2D in youth increased by 7% annually in the U.S. Compared to adults. T2D in adolescents is a much more progressive and recalcitrant disease, characterized by more rapid deterioration of β-cell function and earlier incidence of exogenous insulin dependence and diabetes-related comorbidities. A potential factor that drives the rapid progression of adolescent T2D is obesity (body mass index [BMI] >95th percentile. Effective and safe treatments targeting both obesity and β-cell dysfunction are needed for pediatric T2D. In 2012, the FDA approved the use of Phentermine/Topiramate for the treatment of obesity in adults. This orally-administered medication is available in mid- (phentermine 7.5 mg; topiramate 46 mg) and high- (phentermine 15 mg; topiramate 92 mg) doses, administered once per day. In a meta-analysis, phentermine/topiramate was shown to be one of the most effective obesity medication currently available. A large dose-ranging trial in adults evaluating phentermine and topiramate as monotherapies vs. phentermine/topiramate demonstrated superior efficacy of the combination with an acceptable safety profile. Results from a large phase III clinical trial demonstrated placebo-subtracted weight loss of >9% with treatment for one year at the top dose. Importantly, a separate trial demonstrated that the treatment effect is durable out to at least two years.41 The most common side effects in these trials were paresthesia, dizziness, dysgeusia, insomnia, constipation, and dry mouth. Improvements were noted in blood pressure, lipids, glucose, insulin, HOMA-IR, C-reactive protein, and adiponectin.
Detailed Description
This is a pilot, pragmatic, randomized trial with a 6-month placebo-controlled period followed by a 6-month open-label extension, investigating the effects of phentermine/topiramate on BMI, insulin sensitivity, and glycemic control compared to placebo plus standard treatment (metformin+insulin) in adolescents with T2D. The purpose of this study is to 1) evaluate the effects of phentermine/topiramate vs. placebo+ standard treatment on BMI in adolescents with T2D and obesity and 2) evaluate the effects of phentermine/topiramate vs. placebo + standard treatment on insulin sensitivity and B-cell function in adolescents with T2D and obesity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Obesity

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Model Description
This is a pilot, pragmatic, randomized trial with a 6-month placebo-controlled period followed by a 6-month open label extension investigating the effects of phentermine/topiramate on BMI, insulin sensitivity, and glycemic control compared to placebo plus standard treatment (metformin + insulin) in adolescents with T2D. Individuals, when randomized to phentermine/topiramate therapy will initiate treatment at 3.75 mg/23 mg orally once daily in the morning for 14 days. It will then be increased to 7.5 mg/46 mg orally once daily in the morning for 14 days. It will the be increased to 11.25 mg/69 mg orally once daily in the morning for 14 days and finally to 15 mg/92 mg orally once daily in the morning.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Participants during the first six months of the study will be randomized to receive either phentermine/topiramate or placebo. Neither the participant, care provider, investigator or study team will know whether the participant is receiving phentermine/topiramate or placebo.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo-Controlled Period
Arm Type
Placebo Comparator
Arm Description
Participants in this phase of the study will be randomized 1:1 to receive either phentermine/topiramate or placebo.
Arm Title
Open Label Extension
Arm Type
Experimental
Arm Description
Participants in this phase of the study will receive open label phentermine/topiramate.
Intervention Type
Drug
Intervention Name(s)
Phentermine/Topiramate (Qsymia)
Intervention Description
Maximum dose of 15 mg/92 mg orally once daily in the morning. The dose will be titrated to this level (described earlier).
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Daily injection
Primary Outcome Measure Information:
Title
Change in body mass index
Description
The percent change in body mass index (BMI) from Baseline to Month 6 will be calculated. BMI is defined as a person's weight in kilograms divided by the square of height in meters.
Time Frame
6 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Maximum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ages 12 to </= 20 years at study entry Obesity (BMI >/= the 95th percentile for age and sex) HgbA1c >/= 6.5% at type 2 diabetes diagnosis Negative diabetes auto-antibodies English-speaking and Spanish speaking For participants of child-bearing potential: when sexually active, agreement to use two forms of highly effective contraception (oral contraceptive pill, IUD, implant, and/or condoms) during study participation Exclusion Criteria: Pregnancy or lactation Newly-initiated or change in dose of weight altering medication within past 6 months, including SGLT-2 inhibitors and DPP-IV inhibitors, liraglutide 1.8 mg and exenatide ER. Current or recent (< six months prior to enrollment) use of anti-obesity medication(s) defined as orlistat, phentermine, topiramate, combination PHN/TPM, semaglutide, and/or combination naltrexone/bupropion (monotherapy use of naltrexone or bupropion is not an exclusion) Current use of sulfonylureas Previous metabolic/bariatric surgery Current use of a stimulant medication History of glaucoma Current or recent (< 14 days) use of monoamine oxidase inhibitor or carbonic anhydrase inhibitors Known hypersensitivity to sympathomimetic amines Any history of treatment with growth hormone any history of bulimia nervosa Major psychiatric disorder as determined by the local medical monitor Unstable and clinically-diagnosed (defined as documented in the medical record, if available) depression or PHQ-9 score of >/= 15 Any history of active suicide attempt, a "yes" answer to Question 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) on the "Suicidal Ideation" portion of the C-SSR, or a "yes" to answer to Question 5 (Active Suicidal Ideation with Specific Plan and Intent) on the "Suicidal Ideation" portion of the C-SSRS History of suicidal ideation or self-harm within the previous 30 days or a "yes" answer to any of the suicide-related behaviors (actual attempt, interrupted attempt, aborted attempt, preparatory act, or behavior) on the "Suicidal Behavior" portion of the C-SSRS and the ideation or behavior occurred within the past month. Current pregnancy or plans to become pregnant during study participation Current tobacco use ALT or AST >/= 3 times the upper limit of normal Moderate (Child-Pugh score 7-9) or severe (Child-Pugh score 10-15) Bicarbonate <18 mmol/L Moderate (creatinine clearance [CrCl] greater than or equal to 30 and less than 50 mL/min) or severe (CrCl less than 30 mL/min) renal impairment Any history of seizures • BP for ages 13 and older of > 130/80 on 3 separate measurements and for age 12 > 95th percentile on 3 separate measurements HR ≥120 bpm on 3 separate measurements History of structural heart defect or clinically significant arrhythmia Diagnosed monogenic obesity Any history of cholelithiasis Any history of nephrolithiasis Clinically diagnosed hyperthyroidism Untreated thyroid disorder or TSH below the lower laboratory limit of normal Any disorder, unwillingness, or inability, not covered by any other exclusion criteria, which in the investigator's opinion may put the participant at risk
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Megan Bensignor, MD
Phone
612626-2809
Email
moberle@umn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Megan Bensignor, MD
Organizational Affiliation
University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55414
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Meg Bensignor, MD

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
The protocol, statistical analysis plan and final study report will be released to other researchers but will not contain identifying information.
IPD Sharing Time Frame
10 years after completion of the study

Learn more about this trial

Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity

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