Efficacy and Safety of Phentermine/Topiramate in Youth With Hypothalamic Obesity

Launched by SEATTLE CHILDREN'S HOSPITAL · Mar 1, 2024

Keywords

ClinConnect Summary

This clinical trial is studying the effects of a medication combination called phentermine and topiramate (Ph/T) in young people who have hypothalamic obesity (HO). HO is a type of obesity that can occur after treatment for hypothalamic tumors, which are growths on the brain that can affect weight. Many children and young adults with HO struggle with excessive weight gain and related health problems. The aim of the trial is to see if Ph/T can help reduce weight and improve alertness in participants aged 12 to 28 who have experienced rapid weight gain due to their condition.

To be eligible for the study, participants must be between 12 and 28 years old, have a history of significant weight gain related to their tumor, and meet certain obesity criteria based on their age and sex. Participants should also be stable on other medications for at least two months. The trial will last for 28 weeks and will involve regular check-ups to monitor safety and weight loss. It's important to note that individuals with certain health conditions or who are pregnant or breastfeeding cannot participate. This trial could provide valuable information on how to treat HO in young people, potentially leading to better management of their weight and overall health.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Males and Females; Ages 12-28 years (inclusive)
• • 2. History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist (for example, change in BMI z-score \> 0.2 and/or BMI +5% during the first 6 months following tumor treatment)
• • 3. Obesity (BMI \> 95th%ile for age/sex using CDC 2000 reference for under 18; BMI \> 30 kg/m2 for 18+ years)
• • 4. Recent evidence of hypothalamic injury by brain MRI with central review; \>6 months status-post definitive therapy (surgery, chemotherapy, or radiation); no major operations/surgeries planned during the study period.
• • 5. Stable on pituitary replacement\* and/or appetite-modulating medications (including stimulants) for at least 2 months. \*Adjustments of less than 25% (\<25%) are permitted to hydrocortisone, growth hormone or thyroid hormone. Sex steroids and DDAVP are exempt.
• • 6. Post-menarchal females must use a highly effective form of contraception, unless hypogonadotropic hypogonadism is documented. All participating females will have pregnancy testing as outlined in the protocol.
• • 7. Participants must be able to communicate well with the investigative team, must comply with requirements of the study, and be able to provide written informed consent and/or assent for individuals less than 18y with consent of a parent/legal guardian.
• Exclusion Criteria:
• • 1. Contraindication to Phentermine or Topiramate, as assessed using current package inserts. Including: History of glaucoma and known hyperthyroidism.
• • 2. Known history of metabolic acidosis, low bicarbonate on screening laboratory (below lower limit of normal), or clinically significant bone disease requiring medication (not calcium or vitamin D).
• • 3. Current or recent (\<14 days) use of monoamine oxidase inhibitor.
• • 4. Known hypersensitivity to sympathomimetic amines.
• • 5. Clinically significant cardiovascular conditions, as defined as any of the following: i) abnormal blood pressure, defined as: under 13y, 95th%ile +12 mm Hg or \> 140/90, whichever is lower; 13y and older, \> 140/90 ; ii) history of cardiac arrhythmia or arrhythmia detected on screening ECG; iii) history of heart failure and/or cardiomyopathy; iv) prolonged QTc interval (QTc \> 460 msec), and/or long QT syndrome phenotype and/or positive genotype for long QT syndrome pathogenic; v) history of cardiac disease including coronary artery disease.
• • 6. Females who are pregnant, breastfeeding, or planning to become pregnant during the trial.
• • 7. "Brittle" diabetes insipidus (in the opinion of the referring endocrinologist, e.g. requiring frequent hospitalizations and/or frequent abnormal sodium values).
• • 8. Diabetes mellitus requiring insulin/secretagogue. HbA1c \> 8.5% at Screening.
• • 9. Clinically significant liver disease and/or known severe hepatic impairment. ALT \> 3 x Upper Limit of Normal (ULN) AST \> 3 x ULN
• • 10. Clinically significant kidney disease. GFR\<60 ml/min/1.73m2
• • 11. History of seizure in the 12 months prior to Screening.
• • 12. History of substance abuse, depression of moderate or greater severity, psychiatric disorder and/or suicidality.
• • 13. History of abdominal surgery including gastric bypass.
• • 14. Current use of supra-physiologic steroids.
• • 15. History of allergy or sensitivity to test agents. Including individuals with known aspirin allergy or hypersensitivity and/or known allergy to FD\&C Yellow No. 5 (tartrazine).
• • 16. Concurrent use carbonic anhydrase inhibitor.
• • 17. New weight management medication (or more than 5% decrease in weight over prior 2 months on any current, stable regimen), new stimulant, and/or investigational medication within 2 months prior to Screening, and/or plans to initiate new weight management regimen.
• • 18. Cognitive impairment that, in the opinion of the investigator, precludes participation in the study.
• • 19. Individuals considered, in the Investigator's opinion, otherwise not suitable to participate in the study.