Atomoxetine in Melanocortin Obesity Syndrome

Launched by ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · Mar 21, 2025

Keywords

ClinConnect Summary

Targeted therapies for the treatment of monogenetic obesity are essential because typical lifestyle interventions and standard anti-obesity medications are largely ineffective as they do not correct the specific genetic defect causing abnormal energy balance. The leptin pathway is the key regulator of body weight through control of appetite and energy expenditure. In particular, the severe insatiable hunger experienced by patients with leptin pathway disorders leads not only to extreme obesity, but the unrelenting drive to seek food also causes substantial distress for patients and caregive...

Gender

ALL

Eligibility criteria

• Inclusion criteria:
• • Age 6 years and above
• • Documented MC4R variant classified as pathogenic, likely pathogenic, or variant of uncertain significance per ACMG criteria. If testing was done in a research lab, it will be confirmed by a CLIA-approved lab prior to randomization.
• • Obesity defined as BMI ≥30 kg/m2 in adults or ≥95th percentile for age and sex in children
• Exclusion criteria:
• • Use of atomoxetine, viloxazine (another selective norepinephrine-reuptake inhibitor), methylphenidate, amphetamine, dextroamphetamine, lisdexamfetamine, phentermine, or any other stimulant medication in the past 30 days. If on other ADHD medications, such as guanfacine and clonidine, must be on a stable dose for \>3 months.
• • Weight loss \>5% in the past 3 months.
• • Initiation of new weight loss program, including diet or medications. If on weight loss medications, must be on a stable dose for \>3 months.
• • Inability to swallow capsules.
• • History of hypersensitivity to atomoxetine.
• • Narrow angle glaucoma.
• • History of pheochromocytoma.
• • Uncontrolled Stage 2 hypertension (≥95th percentile + 12 mmHg or \>140/90, whichever is lower) at screening. If on antihypertensive medication, must be on stable dose for \>3 months.
• • Hepatic insufficiency including cirrhosis and acute hepatitis (AST or ALT \>3x upper limit of normal)
• • Uncontrolled asthma requiring albuterol more than once weekly over the past 3 months
• • History of a cardiac arrhythmia (not including bradycardia)
• • Current use of monoamine oxidase inhibitors
• • Pregnancy or intention to become pregnant during the next year
• • History of Major Depressive Disorder in the past 2 years, lifetime history of suicide attempt, history of any suicidal behavior in the past month, history of other severe psychiatric disorders (e.g. schizophrenia, bipolar disorder)
• • PHQ-9 score is ≥15 or suicidal ideation of type 4 or 5 (C-SSR) in the past month
• • Unable to comply with study procedures in the opinion of the investigator

Trial Officials