Recruiting
Phase 2

Atomoxetine

Sponsor:

Icahn School of Medicine at Mount Sinai

Code:

NCT06899178

Conditions

Melanocortin Obesity Syndrome

MCOS

Eligibility Criteria

Sex: All

Age: 6+

Healthy Volunteers: Not accepted

Interventions

Atomoxetine

Placebo

Study Details

Brief 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.

Conditions

Melanocortin Obesity Syndrome

MCOS

Study ID

NCT06899178

Start date

Sep 1, 2026

Status verified date

Aug, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Mar, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 6+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

20 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: Placebo then Atomoxetine

Participants receive placebo for 16 weeks (4 weeks titration + 12 weeks at target dose), followed by washout period, then atomoxetine for 16 weeks (4 weeks titration + 12 weeks at target dose).

active comparator: Atomoxetine then Placebo

Participants receive atomoxetine for 16 weeks (4 weeks titration + 12 weeks at target dose), followed by washout period, then placebo for 16 weeks (4 weeks titration + 12 weeks at target dose).

Interventions

Atomoxetine

Initial dose 40 mg, day 7 dose 60 mg, day 14 dose 80 mg, day 21 dose 100 mg (target dose)

Placebo

Matching placebo oral capsule

Primary outcome measure

  • Body Mass Index (BMI) [ Time Frame: 16 weeks ]

Central Contacts and Locations

Central contacts

Joan C Han, MD

212-241-3744joan.han@mountsinai.org

Locations

Mount Sinai Hospital

Recruiting

New York, New York, United States, 10029

Contacts

Joan Han, MD

212-241-3744joan.han@mountsinai.org

Principal Investigator:

Joan Han

More Information

Sponsor

Icahn School of Medicine at Mount Sinai

Last update posted

Aug 7, 2026

Last verified

Aug, 2026

Keywords

  • Obesity
  • BDNF
  • MC4R
  • Atomoxetine
  • Energy balance
  • Weight loss

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Icahn School of Medicine at Mount Sinai on 2026-08-07.