Schizophenia DisorderPhase 4NCT06740890
Exercise and Olanzapine-samidorphan
A Phase 4 study testing Olanzapine-samidorphan + exercise in people with Schizophenia Disorder and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophenia Disorder, Schizoaffective Disorder, Bipolar Disorder I or II
- What is being tested?
- Olanzapine-samidorphan + exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Jun 2025to Apr 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age between 18-65, inclusive at Visit 1.
- DSM-V diagnosis of schizophrenia or schizoaffective or Bipolar I/II/NOS disorder at Visit 1.
- Body Mass Index (BMI) of 18.0-40.0 kg/m2, inclusive, at Visits 1 and 2.
- Willing to provide informed consent at Visit 1.
- Medically and psychiatrically stable for study participation at Visit 1.
- Responsive to an antipsychotic treatment (other than clozapine) in the past 5 years prior to Visit 1.
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- 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).
- Maintained a stable body weight (change < 5%) for at least 3 months prior to Visit 1.
- 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).
Who cannot join
- Positive drug screen for opioids, phencyclidine, amphetamine/ methamphetamine, or cocaine at Visit 1 or Visit 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.
- 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.
- 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.
- 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.
- 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.
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- 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):
- Clinically significant hypotension or hypertension not stabilized on medical therapy.
- 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).
- 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.
- 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.
- 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.
- 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.
- 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
- Inflammatory bowel disease or any other gastrointestinal disorder associated with weight loss at Visit 1.
- 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.
- History of diabetes (assessed at Visit 1).
- Laboratory abnormality that would compromise the well-being of the subject, or any of the following specific laboratory results at Visit 1:
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) value > 2 times the upper limit of the laboratory normal reference range
- Absolute neutrophil count (ANC) <1.5 x 10^3 μL
- Platelet count < 75 x 10^3 uL
- Serum creatinine > 1.5 mg/dL
- Dyslipidemia, defined for this study as total fasting cholesterol > 280 mg/dL or fasting triglycerides > 500 mg/dL
- Hemoglobin A1c (HbA1c) > 6.0%
- Fasting plasma glucose > 126 mg/dL (7.0 mmol/L)
- Is not fit for the trial in the opinion of the investigator at Visit 1 and Visit 2.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
New York State Psychiatric Institute
New York, New York, 10032
Megan Mayer, BA, 646-774-8477, megan.mayer@nyspi.columbia.edu
About this study
Official title: A Proof of Concept Study of Time Limited Exercise Plus Olanzapine-samidorphan for the Prevention of Early Weight Gain
This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise.
Read the detailed description
The principal hypothesis is that Olz/Sam combined with aerobic exercise will lead to less weight gain than Olz/Sam alone (historical data) when measured at 4 weeks. People with schizophrenia, schizoaffective and bipolar disorder I,II and NOS are eligible.
After informed consent, patients will undergo a full medical/psychiatric screening and be assessed for a reason to switch antipsychotic medication. Eligible subjects will receive 8 weeks of open label Olz/Sam. Over the first 4 weeks of treatment, all subjects will complete 4 weeks of aerobic exercise for 2 to 4 days a week. Olanzapine will be flexibly dosed over the first 4 weeks according to investigator discretion. The Sam dose will remain fixed at 10 mg for the duration of the study.
Subjects will undergo comprehensive weight, metabolic, and symptomatic assessments before and after 4 weeks of exercise, and again at study end (8 weeks). Cognitive assessments will be done at Visit 2/Baseline and study end.
This is a single site study.
- Conditions
- Schizophenia Disorder, Schizoaffective Disorder, Bipolar Disorder I or II, Bipolar Disorder NOS
- Being tested
- Olanzapine-samidorphan + exercise
- Keywords
- Exercise, Antipsychotic induced weight gain, olanzapine-samidorphan
- Medical subject headings
- Psychotic Disorders, Bipolar Disorder, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Olanzapine-samidorphan + exerciseDrug
8 weeks of open label Olanzapine-samidorphan + 4 weeks of aerobic exercise
| Study group | Role | What they receive |
|---|---|---|
| olanzapine-samidorphan plus exercise | Experimental | Not described Receives: Drug: Olanzapine-samidorphan + exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight
Body weight
Measured: 4 weeks
Secondary outcomes (1)
Weight
4 weeks post formal exercise program
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2024
- Study start26 Jun 2025
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Schizophenia DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Joshua Kantrowitz, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06740890
- Sponsor's protocol ID
- 2024-2028
- Status last verified
- Jul 2026
- First submitted
- 14 Dec 2024
- Last updated
- 13 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: non-PHI upon request
Publications
Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, Arndt T, Backers L, Rothe P, Cipriani A, Davis J, Salanti G, Leucht S. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019 Sep 14;394(10202):939-951. doi: 10.1016/S0140-6736(19)31135-3. Epub 2019 Jul 11.
PubMed 31303314Correll CU, Newcomer JW, Silverman B, DiPetrillo L, Graham C, Jiang Y, Du Y, Simmons A, Hopkinson C, McDonnell D, Kahn RS. Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. Am J Psychiatry. 2020 Dec 1;177(12):1168-1178. doi: 10.1176/appi.ajp.2020.19121279. Epub 2020 Aug 14.
PubMed 32791894
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Proof of Concept Study of Time Limited Exercise Plus Olanzapine-samidorphan for the Prevention of Early Weight Gain
- ClinicalTrials.gov ID
- NCT06740890
- Acronym / sponsor ID
- 2024-2028
- Conditions
- Schizophenia Disorder, Schizoaffective Disorder, Bipolar Disorder I or II, Bipolar Disorder NOS
- Keywords
- Exercise, Antipsychotic induced weight gain, olanzapine-samidorphan
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- 26 Jun 2025 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 18 Dec 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single site trial in 30 patients with schizophrenia, schizoaffective, or bipolar I/II/NOS disorder in which all participants will receive eight weeks of olanzapine and samidorphan (Olz/Sam) plus four weeks of aerobic exercise.
Detailed description
The principal hypothesis is that Olz/Sam combined with aerobic exercise will lead to less weight gain than Olz/Sam alone (historical data) when measured at 4 weeks. People with schizophrenia, schizoaffective and bipolar disorder I,II and NOS are eligible.
After informed consent, patients will undergo a full medical/psychiatric screening and be assessed for a reason to switch antipsychotic medication. Eligible subjects will receive 8 weeks of open label Olz/Sam. Over the first 4 weeks of treatment, all subjects will complete 4 weeks of aerobic exercise for 2 to 4 days a week. Olanzapine will be flexibly dosed over the first 4 weeks according to investigator discretion. The Sam dose will remain fixed at 10 mg for the duration of the study.
Subjects will undergo comprehensive weight, metabolic, and symptomatic assessments before and after 4 weeks of exercise, and again at study end (8 weeks). Cognitive assessments will be done at Visit 2/Baseline and study end.
This is a single site study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label
| Arm | Type | Receives |
|---|---|---|
| olanzapine-samidorphan plus exercise | Experimental | Drug: Olanzapine-samidorphan + exercise |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Age between 18-65, inclusive at Visit 1.
- DSM-V diagnosis of schizophrenia or schizoaffective or Bipolar I/II/NOS disorder at Visit 1.
- Body Mass Index (BMI) of 18.0-40.0 kg/m2, inclusive, at Visits 1 and 2.
- Willing to provide informed consent at Visit 1.
- Medically and psychiatrically stable for study participation at Visit 1.
Key exclusion criteria (31 listed)
- Positive drug screen for opioids, phencyclidine, amphetamine/ methamphetamine, or cocaine at Visit 1 or Visit 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.
- 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.
- 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.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Olanzapine-samidorphan + exercise8 weeks of open label Olanzapine-samidorphan + 4 weeks of aerobic exercise | Drug | olanzapine-samidorphan plus exercise |
Primary outcome
Weight
Time frame: 4 weeks
Body weight
1 secondary outcome
Weight
Time frame: 8 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2026.
- Background: PubMed 31303314Huhn M, Nikolakopoulou A, Schneider-Thoma J, Krause M, Samara M, Peter N, Arndt T, Backers L, Rothe P, Cipriani A, Davis J, Salanti G, Leucht S. Comparative efficacy and tolerability of 32 oral antipsychotics for the acute treatment of adults with multi-episode schizophrenia: a systematic review and network meta-analysis. Lancet. 2019 Sep 14;394(10202):939-951. doi: 10.1016/S0140-6736(19)31135-3. Epub 2019 Jul 11.
- Background: PubMed 32791894Correll CU, Newcomer JW, Silverman B, DiPetrillo L, Graham C, Jiang Y, Du Y, Simmons A, Hopkinson C, McDonnell D, Kahn RS. Effects of Olanzapine Combined With Samidorphan on Weight Gain in Schizophrenia: A 24-Week Phase 3 Study. Am J Psychiatry. 2020 Dec 1;177(12):1168-1178. doi: 10.1176/appi.ajp.2020.19121279. Epub 2020 Aug 14.
- Individual participant dataSharing planned: Yes. non-PHI upon request
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Olanzapine-samidorphan + exercise in people with Schizophenia Disorder and Schizoaffective Disorder, run by New York State Psychiatric Institute at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Megan Mayer, BA (646-774-8477, megan.mayer@nyspi.columbia.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06740890, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2026.