Atomoxetine for Obesity

(MCOS Trial)

Recruiting at 1 trial location

Overseen By Joan C Han, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: Icahn School of Medicine at Mount Sinai

Must not be taking: Stimulants, MAO inhibitors

Disqualifiers: Hypertension, Asthma, Depression, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

20 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like atomoxetine, viloxazine, and other stimulant medications for at least 30 days before participating. If you are on other ADHD medications or antihypertensive medications, you must be on a stable dose for more than 3 months.

What data supports the effectiveness of the drug Atomoxetine for obesity?

Research suggests that Atomoxetine, a drug used for ADHD, may help with weight loss because it can suppress appetite. Studies have shown it might be beneficial for people who have gained weight due to certain medications, and it activates pathways in the body that regulate energy and metabolism. ^{1 2 3 4 5}

Is Atomoxetine safe for use in humans?

There is no specific safety data available for Atomoxetine in the context of obesity treatment from the provided research articles. However, Atomoxetine is generally used for other conditions, and any new use should be under medical supervision to ensure safety. ^{3 6 7 8 9}

How does the drug atomoxetine work for obesity?

Atomoxetine is unique for obesity treatment because it is primarily a medication for ADHD that works by increasing norepinephrine levels in the brain, which can help suppress appetite and assist with weight loss. ^{1 2 3 4 10}

What is the purpose of this trial?

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.

Research Team

Joan C Han, MD

Principal Investigator

Mount Sinai Kravis Children's Hospital

Ashley H Shoemaker, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

This trial is for individuals aged 6 and above with obesity linked to MC4R genetic variants. Participants must have a BMI ≥30 kg/m2 (adults) or be in the ≥95th percentile for children, and no major psychiatric disorders, uncontrolled asthma, recent weight loss programs or certain medications. Pregnant women or those planning pregnancy are excluded.

Inclusion Criteria

I am considered obese based on my BMI or my child's BMI is above the 95th percentile for their age and sex.

I am 6 years old or older.

My test shows a specific genetic change linked to weight issues.

Exclusion Criteria

I use my asthma inhaler more than once a week.

Pregnancy or intention to become pregnant during the next year

I have not had major depression, suicide attempts, or severe psychiatric disorders recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atomoxetine or placebo for 16 weeks, with a 4-week titration period followed by 12 weeks at target dose

16 weeks

Crossover

Participants switch treatments after a washout period, receiving the alternate treatment for another 16 weeks

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Atomoxetine

Trial Overview The study tests Atomoxetine against a placebo to see if it's safe and effective for treating obesity related to MC4R gene issues. It's a phase 2 trial where participants randomly receive either the drug or placebo, then switch after some time (crossover design).

Participant Groups

Group I: Atomoxetine then Placebo Active Control 2 Interventions

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).

Group II: Placebo then Atomoxetine Placebo Group 2 Interventions

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).

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Findings from Research

Fluoxetine, when used to treat obesity, has a safety profile similar to that seen in depressed patients, with most adverse events being mild and well tolerated.

No serious adverse events related to fluoxetine were identified, and special evaluations showed no major concerns regarding pharmacokinetics, psychomotor impairment, or addiction potential, indicating minimal risk associated with its use for obesity treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of fluoxetine in the treatment of obesity. Zerbe, RL.[2014]

Obesity is linked to numerous serious health issues, yet the demand for safe and effective antiobesity drugs is rising as obesity rates continue to climb globally.

Previous antiobesity drugs have faced significant safety concerns, leading to withdrawals due to life-threatening side effects, highlighting the need for better predictive models and new therapeutic targets in drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review paper: Current strategies in the development of anti-obesity drugs and their safety concerns. Elangbam, CS.[2008]

Sibutramine and orlistat are two FDA-approved medications for long-term obesity treatment, with distinct mechanisms of action: sibutramine acts as a reuptake inhibitor of monoamines, while orlistat inhibits pancreatic lipase to reduce fat absorption.

Dexfenfluramine has been withdrawn from the market due to its association with serious heart valve issues, highlighting the importance of safety monitoring in obesity pharmacotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent progress in obesity pharmacotherapy. Ryan, DH.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of sibutramine in obese patients: a dose-ranging study. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Atomoxetine for weight reduction in obese women: a preliminary randomised controlled trial. [2015]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of atomoxetine for weight reduction in people with schizophrenia treated with clozapine or olanzapine. [2021]

5. Germany pubmed.ncbi.nlm.nih.gov

The effect of reboxetine co-administration with olanzapine on metabolic and endocrine profile in schizophrenia patients. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Safety of fluoxetine in the treatment of obesity. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Review paper: Current strategies in the development of anti-obesity drugs and their safety concerns. [2008]

8. United States pubmed.ncbi.nlm.nih.gov

Recent progress in obesity pharmacotherapy. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

A risk-benefit assessment of anti-obesity drugs. [2018]

10. Netherlands pubmed.ncbi.nlm.nih.gov

The novel triple monoamine reuptake inhibitor tesofensine induces sustained weight loss and improves glycemic control in the diet-induced obese rat: comparison to sibutramine and rimonabant. [2018]