- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04881799
Phentermine/Topiramate in Adolescents With Type 2 Diabetes and Obesity
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Early Phase 1
Contacts and Locations
Study Contact
- Name: Megan Bensignor, MD
- Phone Number: 612626-2809
- Email: moberle@umn.edu
Study Locations
-
-
Minnesota
-
Minneapolis, Minnesota, United States, 55414
- Recruiting
- University of Minnesota
-
Contact:
- Meg Bensignor, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Sequential Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo-Controlled Period
Participants in this phase of the study will be randomized 1:1 to receive either phentermine/topiramate or placebo.
|
Maximum dose of 15 mg/92 mg orally once daily in the morning.
The dose will be titrated to this level (described earlier).
Daily injection
|
Experimental: Open Label Extension
Participants in this phase of the study will receive open label phentermine/topiramate.
|
Maximum dose of 15 mg/92 mg orally once daily in the morning.
The dose will be titrated to this level (described earlier).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in body mass index
Time Frame: 6 Months
|
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.
|
6 Months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Megan Bensignor, MD, University of Minnesota
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Overnutrition
- Nutrition Disorders
- Overweight
- Body Weight
- Obesity
- Pediatric Obesity
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Autonomic Agents
- Peripheral Nervous System Agents
- Anticonvulsants
- Appetite Depressants
- Anti-Obesity Agents
- Central Nervous System Stimulants
- Sympathomimetics
- Topiramate
- Phentermine
Other Study ID Numbers
- PEDS-2021-29785
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Pediatric Obesity
-
Virginia Commonwealth UniversityActive, not recruitingObesity, PediatricUnited States
-
University of British ColumbiaThe Hospital for Sick Children; Canadian Institutes of Health Research (CIHR); Alberta Health services and other collaboratorsCompleted
-
Hasselt UniversityJessa HospitalCompletedObesity, Pediatric
-
Azienda Ospedaliera Universitaria Integrata VeronaNot yet recruitingObesity, Pediatric
-
University of British ColumbiaHeart and Stroke Foundation of Canada; Public Health Agency of Canada (PHAC); Childhood Obesity Foundation and other collaboratorsCompleted
-
Columbia UniversityCompletedVitamin D Deficiency | Obesity, Morbid | Obesity, Childhood | Obesity, PediatricUnited States
-
University Hospital, Clermont-FerrandAME2P Laboratory, Clermont Auvergne UniversityCompleted
-
Medical College of WisconsinWisconsin Department of Health and Family Services; Children's Health System...TerminatedPediatric Obesity | Pediatric OverweightUnited States
-
Kahramanmaras Sutcu Imam UniversityCompletedPediatric Obesity | Pediatric DentistryTurkey
-
Central Hospital, Nancy, FranceNot yet recruiting
Clinical Trials on Phentermine/Topiramate (Qsymia)
-
University of MinnesotaRecruiting
-
Wake Forest University Health SciencesVIVUS LLCCompletedObesity | Weight Loss | Metabolic Surgery | Bariatric Surgery ProceduresUnited States
-
Mayo ClinicNational Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Completed
-
Stanford UniversityCompletedBulimia Nervosa | Binge Eating DisorderUnited States
-
Denver Health and Hospital AuthorityCompleted
-
VIVUS LLCCompletedBlood PressureUnited States
-
Mayo ClinicCompleted
-
Seattle Children's HospitalChildren's Hospital of PhiladelphiaNot yet recruitingCraniopharyngioma | Hypothalamic Obesity | Hypothalamic TumorUnited States
-
VIVUS LLCCompleted
-
VIVUS LLCCompletedAdolescent Obesity | Obesity in Adolescence | Adolescent OverweightUnited States