A Phase 2, Double Blind, Randomized, Placebo-controlled Crossover Trial to Evaluate the Efficacy and Safety of Atomoxetine in Adults With Melanocortin Obesity Syndrome
Icahn School of Medicine at Mount Sinai
Summary
This is a phase 2 randomized placebo-controlled crossover trial to determine the safety and efficacy of atomoxetine for treating obesity caused by loss-of-function variants in the melanocortin-4 receptor (MC4R), the most common cause of genetic obesity disorders. Atomoxetine was selected for this pilot trial because it has been shown to increase brain-derived neurotrophic factor (BDNF) within the central nervous system and in peripheral circulation. Targeting BDNF is a specific strategy for treating MC4R abnormalities because BDNF functions as a downstream mediator of MC4R signaling.
Description
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 caregivers.…
Eligibility
- Age range
- 6+ years
- Sex
- All
- Healthy volunteers
- No
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 t…
Interventions
- DrugAtomoxetine
Initial dose 40 mg, day 7 dose 60 mg, day 14 dose 80 mg, day 21 dose 100 mg (target dose)
- DrugPlacebo
Matching placebo oral capsule
Locations (2)
- Mount Sinai HospitalNew York, New York
- Vanderbilt University Medical CenterNashville, Tennessee