Atomoxetine in Melanocortin Obesity Syndrome
Recruiting · NCT06899178 · Interventional (participants receive a specific treatment)
View the official record on ClinicalTrials.gov →Interventions studied
AtomoxetinePlacebo
What this trial is about
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.
Who can take part
Age range
6 Years and older
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 2
Study type
Interventional (participants receive a specific treatment)
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
Where it is running
3 locations listed across 3 US states.
- Mount Sinai Hospital - New York, New York, United States
- Nationwide Children's Hospital - Columbus, Ohio, United States
- Vanderbilt University Medical Center - Nashville, Tennessee, United States