Atomoxetine in Melanocortin Obesity Syndrome

ID#: NCT06899178

Age: 6 years - 66+

Gender: All

Healthy Subjects: No

Study Phase: Phase 2

Recruitment Status: Recruiting

Start Date: September 01, 2026

End Date: June 01, 2028

Contact Information:
Joan C Han, MD
212-241-3744
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.
Eligibility:

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
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