Atomoxetine for Obesity

(MCOS Trial)

Not yet 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of atomoxetine, a medication typically used for ADHD, in treating obesity linked to a genetic issue with the melanocortin-4 receptor (MC4R), a common cause of genetic obesity. Atomoxetine may help by boosting a brain-related factor involved in MC4R signaling. Participants will receive atomoxetine or a placebo in different sequences to assess the effects. Ideal candidates for this trial have a documented MC4R genetic variant and have been living with obesity. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important early findings.

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.

Is there any evidence suggesting that atomoxetine is likely to be safe for humans?

Research has shown that atomoxetine is generally safe for people. Studies involving individuals with various conditions have found atomoxetine to be safe in different contexts. For instance, one study found that atomoxetine helped individuals with ADHD without major safety concerns. Another study combined atomoxetine with another drug to address sleep-related breathing issues, and it was considered safe.

Atomoxetine is also under investigation for weight management. An early study demonstrated modest weight loss in obese women compared to a placebo, with no major safety issues reported. Since atomoxetine is already approved for treating ADHD, this adds some confidence in its safety. However, as this trial is in the early stages, the complete safety for obesity treatment is still being researched. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Unlike the standard obesity treatments that often focus on appetite suppression or fat absorption, atomoxetine is unique because it targets the brain's norepinephrine system, which is typically involved in attention disorders. This novel mechanism of action could potentially help regulate both appetite and metabolic rate more effectively. Researchers are excited about atomoxetine because it offers a new approach that might address obesity from a neurological angle, providing an alternative for those who may not respond well to existing therapies like orlistat or phentermine. Additionally, the ability to switch between atomoxetine and a placebo in the study allows for a clearer understanding of its direct impact on weight management.

What evidence suggests that atomoxetine might be an effective treatment for obesity?

Research has shown that atomoxetine might help individuals with genetic obesity linked to the MC4R gene lose weight. For example, one teenager's BMI decreased from 47.2 to 29.6 kg/m² after taking atomoxetine. Another study found that obese women lost weight with atomoxetine compared to those on a placebo. In this trial, participants will receive either atomoxetine followed by a placebo or a placebo followed by atomoxetine. Atomoxetine likely works by boosting a brain chemical called BDNF, which is crucial for MC4R function. These findings suggest that atomoxetine could benefit those with obesity related to MC4R issues. ^{1 2 6 7 8}

Who Is on the Research Team?

Ashley H Shoemaker, MD, MSCI

Principal Investigator

Vanderbilt University Medical Center

Joan C Han, MD

Principal Investigator

Mount Sinai Kravis Children's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/16418753/

Atomoxetine for weight reduction in obese women Atomoxetine demonstrated modest short-term weight loss efficacy relative to placebo in this preliminary study of obese women.

2. psychiatry-psychopharmacology.com psychiatry-psychopharmacology.com/Content/files/sayilar/19/The%20effects%20of%20atomoxetine%20on%20weight%20height%20and%20body%20mass%20index%20in%20Turkish%20children%20and%20adolescents%20with%20attention%20deficit%20hyperactivity%20disorder.pdf

The effects of atomoxetine on weight height and body mass ... Results: Atomoxetine treatment was associated with a notional reduction in height and weight standard deviation scores (SDS). There were no ...

3. karger.com karger.com/ofa/article/6/1/109/239950/Successful-Treatment-with-Atomoxetine-of-an

Successful Treatment with Atomoxetine of an Adolescent ... The boy markedly reduced his BMI from 47.2 to 29.6 kg/m². Conclusion: Atomoxetine proved to efficiently reduce weight in a severely obese MC4R ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06899178

Atomoxetine in Melanocortin Obesity Syndrome (MCOS) The FDA effectiveness threshold for anti-obesity medication is 5% weight loss after 12 weeks. The half-life of atomoxetine is approximately 5 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23493066/

Successful treatment with atomoxetine of an adolescent ... The boy markedly reduced his BMI from 47.2 to 29.6 kg/m². Conclusion: Atomoxetine proved to efficiently reduce weight in a severely obese MC4R ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8863678/

The Mechanism, Clinical Efficacy, Safety, and Dosage ... The atomoxetine groups had superior outcomes in ADHD symptoms compared with placebo group. Social and family functions were also significantly improved in the ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S001236922505384X

Acetazolamide Plus Atomoxetine for Obesity ... Interpretation: Acetazolamide plus atomoxetine was safe and effective in improving hypoventilation and sleep-related breathing in patients with ...

8. tandfonline.com tandfonline.com/doi/full/10.1080/24750573.2019.1637393

The effects of atomoxetine on weight, height, and body ... Results: Atomoxetine treatment was associated with a notional reduction in height and weight standard deviation scores (SDS). There were no ...