SchizophreniaPhase 4NCT03526354
Controlled Trial of Brexpiprazole For The Treatment of Co-occurring Schizophrenia and Substance Use Disorder
A Phase 4 study testing Brexpiprazole and Treatment as Usual in people with Schizophrenia and Schizoaffective Disorder, run by University of Massachusetts, Worcester at 4 sites in United States.
Trial summary
The proposed study is a 4-site, 12-week, novel, feasibility, investigation of patients who have co-occurring diagnoses of schizophrenia and current substance use disorder (alcohol, cocaine, heroin, or cannabis). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Substance Use Disorders
- What is being tested?
- Brexpiprazole and Treatment as Usual
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 4 sitesUnited States
- Study dates
- 19 Jun 2018to 29 Feb 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18-65 years old
- Meets the DSM-5 criteria for diagnoses of schizophrenia or schizoaffective disorder and substance use disorder (alcohol, cocaine, heroin, or cannabis) based on the Mini International Neuropsychiatric Interview for the DSM-5 (MINI 7.0)
- Uses substance on at least 4 of the past 30 days prior to randomization with at least one use in the week prior to randomization for one of substances (cocaine, heroin, cannabis or alcohol) assessed by the TLFB interview
- Stable dose of antipsychotic agent for at least one month
- Well established compliance with outpatient medications
- Female subjects of child-bearing potential are required to practice appropriate birth control methods during the study.
Who cannot join
- Psychiatrically unstable
- Currently meets DSM-5 criteria for any substance use disorder other than caffeine, nicotine, alcohol, cocaine, heroin and cannabis
- Significant, unstable medical conditions including severe cardiovascular, hepatic, renal or other medical diseases
- History of a seizure disorder
- Pregnancy or breastfeeding
- Currently on aripiprazole or cariprazine
- Currently on medications to treat substance use (disulfiram, naltrexone, acamprosate, methadone, buprenorphine, varenicline or buproprion)
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Augusta University
Augusta, Georgia, 30912
Massachusetts General Hospital
Boston, Massachusetts, 02114
University of North Carolina
Chapel Hill, North Carolina, 27599
UMass Medical School
Worcester, Massachusetts, 01655
About this study
Official title: A Multi-center, Randomized, Controlled Trial of Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use Disorder
The proposed study is a 4-site, 12-week, novel, feasibility, investigation of patients who have co-occurring diagnoses of schizophrenia and current substance use disorder (alcohol, cocaine, heroin, or cannabis). Thirty-nine participants will be randomly assigned to switch to brexpiprazole (the brexpiprazole group) or remain on the same antipsychotic treatment (the control group). The study will be conducted at 4 sites in the US. The investigators expect to enroll 80 subjects across 3 sites. UMass Medical School, Worcester MA is the lead site. Sub-sites include Massachusetts General Hospital (MGH) and the University of North Carolina at Chapel Hill (UNC).
Read the detailed description
STUDY OBJECTIVES
The primary objectives of the study include:
- examine the effect of brexpiprazole treatment on the number of days of substance use in the past week as measured by the Timeline Follow-Back (TLFB) assessment;
- examine the effect of brexpiprazole treatment on substance craving using 100-mm visual analogue scale (VAS).
The secondary objectives are to examine the effect of brexpiprazole treatment on:
- the dollar amount spent on substances in the past week;
- the psychiatric symptoms as measured by various clinical rating scales
- quality of life
- Being tested
- Brexpiprazole, Treatment as Usual
- Keywords
- Schizophrenia, Schizoaffective Disorder, Substance Use Disorders, Alcohol Use Disorder, Cannabis Use Disorder, Cocaine Use Disorder, Heroin Use Disorder
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Substance-Related Disorders, Alcoholism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BrexpiprazoleDrug
Also called Study Medication
Brexpiprazole 4mg daily for 12 weeks
Treatment as UsualOther
Also called Current Antipsychotic Treatment
Current antipsychotic medication for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Experimental | Experimental | Brexpiprazole 4mg daily for 12 weeks Receives: Drug: Brexpiprazole |
| Treatment as Usual | Active comparator | Stay on current antipsychotic medication for 12 weeks Receives: Other: Treatment as Usual |
What is being measured
The primary outcome is the main question the study is designed to answer.
Timeline Follow Back (TLFB)
The Timeline Follow Back (TLFB) scale is used to measure weekly substance use for alcohol, marijuana, cocaine, and/or heroin by assessing the number of days a person used substances in the past week, on a scale from 0 to 7 [0 = no substances that week; 7 = substance use every day]. The outcome measure was the number of days per week that participants used a substance. If participants use more than one substance, only the primary substance (one used mostly frequently) was analyzed.
While the TLFB was assessed weekly, the outcome measure reported is the change in substance use between Week 0 (Baseline) and Week 12 (End of Study). A decrease in number of days/week that substances were used indicates an improved (better) outcome.
While the TLFB was assessed weekly, the outcome measure reported is the change in substance use between Week 0 (Baseline) and Week 12 (End of Study). A decrease in number of days/week that substances were used indicates an improved (better) outcome.
Measured: 12 weeks
Visual Analog Scale (VAS)
The Visual Analog Scale (VAS) measures substance craving. Subjects will make a mark on an unlabeled 100-millimeter line indicating their desire to use a particular substance over the past 7-days. A score of 0 indicates no desire to use and 100 indicating the strongest desire to use possible. The assessment was done weekly. Subjects reported craving for any substances they used that week with a separate mark for each substance (e.g., a mark for alcohol craving and another mark for marijuana). For outcome measures, only the primary substance (the substance used most frequently, as determined by the Timeline Follow Back assessment) was included. While cravings were assessed weekly, only the change in craving from Week 0 (Baseline) to Week 12 (End of Study) is reported; a decreased score (reduction in cravings) represents an improved outcome.
Measured: 12 weeks
Secondary outcomes (4)
Amount of Money Spent on Substances
The amount of money spent on substances over a 7-day period will also be recorded as part of each weekly visit. Decreased money spent on substances over a 7-day period will also be considered an improved outcome.
Measured: 12 weeks
Positive and Negative Symptom Scale (PANSS)
The Positive and Negative Symptom Scale (PANSS) is a measure used to assess symptom severity in patients with schizophrenia. Each item (symptom) is scored on a 7-point scale (1 = absent and 7 = extreme). The minimum and maximum values for the total 30 items (PANSS Total Score) are 30 and 210 respectively. Higher scores represent higher levels of psychiatric symptoms (worse outcomes).
The PANSS has three subscales: "Positive" (measuring positive symptoms), "Negative" (measuring negative symptoms), and "General Psychopathology" (measuring general psychiatric symptoms). There are 7 items each for Positive and Negative subscales (minimum value for each is 7, and maximum value is 49), and 16 items for General Psychopathology (minimum value is 16 and maximum is 112).
This study looked at changes in all 3 subscales and the PANSS total score between Week 0 (Baseline) and Week 12 (End of Study), with a decrease in score indicating improved psychiatric functioning.
Measured: 12 Weeks
Clinical Global Impression - Severity
The Clinical Global Impression - Severity (CGI-S) measures illness severity on a 7-point Likert scale, with a higher score indicating higher illness severity and worse outcomes (1 = "Normal, not at all ill" and 7 = "Among the most extremely ill patients"). The outcome measure for this study looked at the change in the CGI-S score between Week 0 (Baseline) and Week 12 (end of study), with a reduction in score indicating improved outcomes.
Measured: 12 Weeks
Heinrichs Carpenter Quality of Life Scale (QOL)
The Heinrichs Carpenter Quality of Life Scale (QOL)is a 21-item scale providing information on symptoms and functioning in patients with schizophrenia. Items are scored on a 0-6 scale, with 0 being no evidence of that item (e.g., social relationships are virtually absent) and 6 being adequate evidence of that item (e.g., adequate social relationships). Two items (#1 - "Intimate relationship with household members" and # 12 - "Satisfaction with occupational role functioning") are scored a "9" if the item is not applicable (e.g., lives alone with no close family or does not have an occupational role). Therefore, total scores can range from 0 to 132 (if 9s are scored). A higher total score indicates better psychosocial functioning.
For this study, the outcome measure looked at the change in total score between Week 0 and Week 12.
Measured: 12 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2018
- Study start19 Jun 2018
- Primary completion29 Feb 2024
- Study completion29 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by University of Massachusetts, WorcesterThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Massachusetts, Worcester
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital, University of North Carolina, Chapel Hill, Otsuka Pharmaceutical Co., Ltd., Augusta University
- Responsible party
- Principal investigator, Xiaoduo Fan, MD, MPH, University of Massachusetts, Worcester
- Investigators
- Xiaoduo Fan, MD, Principal investigator, University of Massachusetts, Worcester
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03526354
- Sponsor's protocol ID
- 14611
- Status last verified
- May 2025
- First submitted
- 3 May 2018
- Last updated
- 23 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Fan X, Freudenreich O, Jarskog LF, McEvoy J, Harrington A. Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use Disorder: A Multisite, Randomized, Controlled Trial. J Clin Psychiatry. 2025 Oct 13;86(4):25m15786. doi: 10.4088/JCP.25m15786.
PubMed 41129678
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multi-center, Randomized, Controlled Trial of Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use Disorder
- ClinicalTrials.gov ID
- NCT03526354
- Acronym / sponsor ID
- 14611
- Keywords
- Schizophrenia, Schizoaffective Disorder, Substance Use Disorders, Alcohol Use Disorder, Cannabis Use Disorder, Cocaine Use Disorder, Heroin Use Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of Massachusetts, WorcesterUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital, University of North Carolina, Chapel Hill, Otsuka Pharmaceutical Co., Ltd., Augusta University
- Study start
- 19 Jun 2018 (actual)
- Primary completion
- 29 Feb 2024 (actual)
- Study completion
- 29 Feb 2024 (actual)
- First posted
- 16 May 2018 (actual)
- Results
- Posted 23 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The proposed study is a 4-site, 12-week, novel, feasibility, investigation of patients who have co-occurring diagnoses of schizophrenia and current substance use disorder (alcohol, cocaine, heroin, or cannabis). Thirty-nine participants will be randomly assigned to switch to brexpiprazole (the brexpiprazole group) or remain on the same antipsychotic treatment (the control group). The study will be conducted at 4 sites in the US. The investigators expect to enroll 80 subjects across 3 sites. UMass Medical School, Worcester MA is the lead site. Sub-sites include Massachusetts General Hospital (MGH) and the University of North Carolina at Chapel Hill (UNC).
Detailed description
STUDY OBJECTIVES
The primary objectives of the study include:
- examine the effect of brexpiprazole treatment on the number of days of substance use in the past week as measured by the Timeline Follow-Back (TLFB) assessment;
- examine the effect of brexpiprazole treatment on substance craving using 100-mm visual analogue scale (VAS).
The secondary objectives are to examine the effect of brexpiprazole treatment on:
- the dollar amount spent on substances in the past week;
- the psychiatric symptoms as measured by various clinical rating scales
- quality of life
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental | Experimental | Drug: BrexpiprazoleBrexpiprazole 4mg daily for 12 weeks |
| Treatment as Usual | Active comparator | Other: Treatment as UsualStay on current antipsychotic medication for 12 weeks |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-65 years old
- Meets the DSM-5 criteria for diagnoses of schizophrenia or schizoaffective disorder and substance use disorder (alcohol, cocaine, heroin, or cannabis) based on the Mini International Neuropsychiatric Interview for the DSM-5 (MINI 7.0)
- Uses substance on at least 4 of the past 30 days prior to randomization with at least one use in the week prior to randomization for one of substances (cocaine, heroin, cannabis or alcohol) assessed by the TLFB interview
- Stable dose of antipsychotic agent for at least one month
- Well established compliance with outpatient medications
Key exclusion criteria (7 listed)
- Psychiatrically unstable
- Currently meets DSM-5 criteria for any substance use disorder other than caffeine, nicotine, alcohol, cocaine, heroin and cannabis
- Significant, unstable medical conditions including severe cardiovascular, hepatic, renal or other medical diseases
- History of a seizure disorder
- Pregnancy or breastfeeding
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 |
|---|---|---|
| BrexpiprazoleAlso: Study MedicationBrexpiprazole 4mg daily for 12 weeks | Drug | Experimental |
| Treatment as UsualAlso: Current Antipsychotic TreatmentCurrent antipsychotic medication for 12 weeks | Other | Treatment as Usual |
Primary outcome
Timeline Follow Back (TLFB)
Time frame: 12 weeks
The Timeline Follow Back (TLFB) scale is used to measure weekly substance use for alcohol, marijuana, cocaine, and/or heroin by assessing the number of days a person used substances in the past week, on a scale from 0 to 7 [0 = no substances that week; 7 = substance use every day]. The outcome measure was the number of days per week that participants used a substance. If participants use more than one substance, only the primary substance (one used mostly frequently) was analyzed. While the TLFB was assessed weekly, the outcome measure reported is the change in substance use between Week 0 (Baseline) and Week 12 (End of Study). A decrease in number of days/week that substances were used indicates an improved (better) outcome. While the TLFB was assessed weekly, the outcome measure reported is the change in substance use between Week 0 (Baseline) and Week 12 (End of Study). A decrease in number of days/week that substances were used indicates an improved (better) outcome.
Visual Analog Scale (VAS)
Time frame: 12 weeks
The Visual Analog Scale (VAS) measures substance craving. Subjects will make a mark on an unlabeled 100-millimeter line indicating their desire to use a particular substance over the past 7-days. A score of 0 indicates no desire to use and 100 indicating the strongest desire to use possible. The assessment was done weekly. Subjects reported craving for any substances they used that week with a separate mark for each substance (e.g., a mark for alcohol craving and another mark for marijuana). For outcome measures, only the primary substance (the substance used most frequently, as determined by the Timeline Follow Back assessment) was included. While cravings were assessed weekly, only the change in craving from Week 0 (Baseline) to Week 12 (End of Study) is reported; a decreased score (reduction in cravings) represents an improved outcome.
4 secondary outcomes
Amount of Money Spent on Substances
Time frame: 12 weeks
Positive and Negative Symptom Scale (PANSS)
Time frame: 12 Weeks
Clinical Global Impression - Severity
Time frame: 12 Weeks
Heinrichs Carpenter Quality of Life Scale (QOL)
Time frame: 12 Weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41129678Fan X, Freudenreich O, Jarskog LF, McEvoy J, Harrington A. Brexpiprazole for the Treatment of Co-occurring Schizophrenia and Substance Use Disorder: A Multisite, Randomized, Controlled Trial. J Clin Psychiatry. 2025 Oct 13;86(4):25m15786. doi: 10.4088/JCP.25m15786.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Xiaoduo Fan, MD principal investigator
University of Massachusetts, Worcester
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Brexpiprazole and Treatment as Usual in people with Schizophrenia and Schizoaffective Disorder, run by University of Massachusetts, Worcester at 4 sites 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 6 inclusion and 7 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: finished, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Yes. Results are posted in the registry (first posted 23 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Timeline Follow Back (TLFB) (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT03526354, which also lists 1 linked publication.
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 23 May 2025.