Atomoxetine in Melanocortin Obesity Syndrome

NCT06899178 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: GCO 24-0669
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Body Mass Index (BMI)

  BMI will be calculated as kg/sq m. The sex appropriate CDC growth chart will be used to calculate BMI as a percent of the 95th percentile (BMI95). For patients \>20 years, the 20-year-old percentiles will be used.

  16 weeks

Secondary Outcomes (12)

• Resting Energy Expenditure (REE)

  16 weeks

• Healthy Eating Index (HEI)

  16 weeks

• Hyperphagia Questionnaire (HQ)

  16 weeks

• Hunger and Satiety Score

  16 weeks

• Fasting Glucose Level

  At week 0, week 16 and week 32.

Study Arms (2)

Placebo then Atomoxetine

PLACEBO COMPARATOR

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).

Drug: Atomoxetine; Drug: Placebo

Atomoxetine then Placebo

ACTIVE COMPARATOR

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).

Drug: Atomoxetine; Drug: Placebo

Interventions

Atomoxetine DRUG

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

Atomoxetine then Placebo; Placebo then Atomoxetine

Placebo DRUG

Matching placebo oral capsule

Atomoxetine then Placebo; Placebo then Atomoxetine

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• Vanderbilt University Medical Center: collaborator

Study Sites (2)

Mount Sinai Hospital

New York, New York, 10029, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Conditions

Obesity; Weight Loss

Interventions

Atomoxetine Hydrochloride

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Joan C Han, MD

  Mount Sinai Kravis Children's Hospital

  PRINCIPAL INVESTIGATOR

• Ashley H Shoemaker, MD, MSCI

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joan C Han, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Pediatrics

Model Details: A randomized, placebo-controlled, crossover study of atomoxetine. The treatment periods will last 16 weeks, separated by a 2-week washout period. Atomoxetine immediate release is approved for treatment of ADHD in children and adults. Enrollment will be based on age groups in batches, beginning with 10 adults, to optimize the protocol and monitor safety/efficacy before treating younger patients. If safety and efficacy are acceptable, the pediatric cohort will be enrolled. The intervention length of 16 weeks per arm was chosen to allow for 4 weeks of dose titration and 12 weeks exposure to target dose. The FDA effectiveness threshold for anti-obesity medication is 5% weight loss after 12 weeks. The half-life of atomoxetine is approximately 5 hours. A two-week washout period will allow for elimination of study drug while minimizing participant burden from frequent study visits.

Study Record Dates

• First Submitted: March 21, 2025
• First Posted: March 27, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2028
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• Access Criteria: Researchers who provide a methodologically sound proposal. To achieve aims in the approved proposal. Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (Link to be included in the URL field below).

Locations

US (2)