Can a short exercise program stop antipsychotic weight gain?

NCT ID NCT06740890

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This trial is taking on new participants right now.
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Registered, but not yet taking participants.
By invitation only
Not open to general applications. Only people the study team invites can take part.
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Paused for now. It may or may not start again.
Ongoing
Running, but no longer taking on new participants.
Completed
The trial has finished. Results may not be published yet.
Stopped early
Stopped early, before it reached the end. That can be for many reasons, including safety.
Cancelled
Cancelled before anyone took part.

Expanded access (not trials)

Expanded access
Not a trial. This treatment can be requested outside a study, case by case, for people who qualify.
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Expanded access (ended)
Not a trial. The treatment could once be requested outside a study, but no longer can.
Approved
The treatment has been approved, so it is available normally rather than through this programme.

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First seen Jul 13, 2026 · Last updated Jul 14, 2026 · Updated 1 time

Summary

This study tests whether adding a four-week aerobic exercise program to a new antipsychotic medication (olanzapine-samidorphan) can prevent the early weight gain often seen with these drugs. Thirty adults with schizophrenia, schizoaffective disorder, or bipolar disorder will take the medication for eight weeks and exercise for the first four weeks. The main goal is to see if participants gain less weight than expected.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance
Olanzapine-samidorphan plus aerobic exercise
What this could lead to
If successful, this approach could help prevent the rapid weight gain often caused by antipsychotic medications, improving long-term health outcomes.
What could go wrong
This is a small, early-phase study with only 30 participants, so results may not apply broadly. The exercise program is short (4 weeks), and weight gain prevention may not persist.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 4

Runs after approval, following long-term safety and how well the treatment works in everyday use.

Participants

About 30 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jun 2025

Expected to finish

Apr 2027

An estimate. End dates often move.

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 65 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Age between 18-65, inclusive at Visit 1. 2. DSM-V diagnosis of schizophrenia or schizoaffective or Bipolar I/II/NOS disorder at Visit 1. 3. Body Mass Index (BMI) of 18.0-40.0 kg/m2, inclusive, at Visits 1 and 2. 4. Willing to provide informed consent at Visit 1. 5. Medically and psychiatrically stable for study participation at Visit 1. 6. Responsive to an antipsychotic treatment (other than clozapine) in the past 5 years prior to Visit 1. 7. Can benefit from participation in this study and has a reason to participate, such as inadequate efficacy on current treatment, side effects on current treatment, desire to start olanzapine-samidorphan or try structured exercise program (assessed at Visit 1). 8. Maintained a stable body weight (change \< 5%) for at least 3 months prior to Visit 1. 9. Willing to use qualified methods of contraception (listed in section 5.3) for the study duration (for women of childbearing potential only) (assessed at Visit 1 and Visit 2). Exclusion Criteria: 1. Positive drug screen for opioids, phencyclidine, amphetamine/ methamphetamine, or cocaine at Visit 1 or Visit 2. 2. Diagnosis of moderate or severe substance use disorder, anorexia nervosa, bulimia, binge eating disorder or any other clinically significant eating disorder at Visit 1. 3. EKG abnormality that is clinically significant including a QT interval \> 450 msec for men and \> 470 msec for women, as corrected by the Fridericia formula (QTcF) at Visit 1. 4. Use of olanzapine+samidorphan for any reason in the last six months prior to Visit 1, any history of poor or inadequate response to treatment with olanzapine or no justifiable reason to expect improvement on olanzapine as assessed at Visit 1. 5. Taken opioid agonists (e.g., codeine, oxycodone, tramadol, or morphine) within the 14 days prior to Visit 1 and/or anticipates a need to take opioid medication during the study period (e.g., planned surgery), or has taken opioid antagonists including naltrexone (any formulations) or naloxone within 60 days prior to Visit 1. 6. Pregnant or breast feeding women. Women of child-bearing potential must have a negative serum beta-hCG pregnancy test at Visit 1 and a negative urine pregnancy test at Visit 2. 7. Any clinically significant or unstable medical illness, condition, or disorder that is anticipated to potentially compromise subject safety on study medication or exercise, or adversely affect the evaluation of efficacy, including (but not necessarily limited to) the following (as assessed at Visit 1): 1. Clinically significant hypotension or hypertension not stabilized on medical therapy. 2. Unstable thyroid dysfunction in the past 6 months (e.g., hypothyroidism, hyperthyroidism, or thyroiditis that was untreated, or discovered and treatment was initiated within the 6 months prior to screening). 3. Personal or family history of neuroleptic malignant syndrome, has a history of clinically significant extrapyramidal symptoms when taking olanzapine, or has had clinically significant tardive dyskinesia. 4. Neurological conditions include the following: * History of seizure disorder or a condition associated with seizures (except history of febrile seizures). * History of brain tumor, subdural hematoma, stroke or any other clinically significant neurological condition within the 12 months prior to Visit 1. * Head trauma with loss of consciousness within the 12 months prior to Visit 1. * Active, acute or chronic CNS infection. 5. Cardiac condition that might confound study results, pose additional risk when administering the study drug or exercise regimen to the subject, or preclude successful completion of the study. Conditions include the following: * Clinically significant cardiac arrhythmia, cardiomyopathy, a cardiac conduction defect, or a history of myocardial infarction or unstable angina within 6 months prior to Visit 1. 8. Currently taking any contraindicated medications as per the approved labeling for Olz-Sam (see section 6.5 for details) at Visit 1 and Visit 2. 9. Subjects with suicidal ideation with intent or plan (indicated by affirmative answers to items 4 or 5 of the Suicidal Ideation section of the baseline C-SSRS) in the 3 months prior to Visit 1 or current at Visit 2 10. Inflammatory bowel disease or any other gastrointestinal disorder associated with weight loss at Visit 1. 11. Joined a weight management program or had significant changes in diet or exercise regimen within 6 weeks prior to Visit 1 or plans to join a weight management program during the study as assessed at Visit 1. 12. History of diabetes (assessed at Visit 1). 13. Laboratory abnormality that would compromise the well-being of the subject, or any of the following specific laboratory results at Visit 1: 1. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value \> 2 times the upper limit of the laboratory normal reference range 2. Absolute neutrophil count (ANC) \<1.5 x 10\^3 μL 3. Platelet count \< 75 x 10\^3 uL 4. Serum creatinine \> 1.5 mg/dL 5. Dyslipidemia, defined for this study as total fasting cholesterol \> 280 mg/dL or fasting triglycerides \> 500 mg/dL 6. Hemoglobin A1c (HbA1c) \> 6.0% 7. Fasting plasma glucose \> 126 mg/dL (7.0 mmol/L) 14. Is not fit for the trial in the opinion of the investigator at Visit 1 and Visit 2.

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Conditions

The condition(s) this trial relates to.

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

How to take part

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  1. The places running it

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  2. The official record

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Contacts and locations

Locations

  • New York State Psychiatric Institute

    RECRUITING

    New York, New York, 10032, United States

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