SchizophreniaPhase 2NBCNCT03132571
Naltrexone-Bupropion Versus Placebo-Bupropion for Weight Loss in Schizophrenia
A Phase 2 study testing Naltrexone and Bupropion in people with Schizophrenia and Diabetes Mellitus, Type 2, run by Yale University at 1 site in United States.
Trial summary
The purpose of this study is to determine the efficacy of combining open-label extended release bupropion (flexible dosing up to 450mg target) and naltrexone (37.5mg) versus Bupropion and placebo along with a daily 500 calorie reduction diet recommendation for weight and health risk reduction in 40 overweight/obese… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Schizophrenia, Diabetes Mellitus, Type 2, Obesity
- What is being tested?
- Naltrexone and Bupropion
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2017to 31 Jul 2018
- Phase
- Phase 2
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 75
- Meet DSM-IV criteria for schizophrenia or schizoaffective disorder based on SCID interview (If bipolar-schizoaffective: need to be adequately stabilized on a mood stabilizer and show no mania history for the past one year, as confirmed by study psychiatrist and patient's clinician)
- Body Mass Index (BMI) of 28 and over
- On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch
- Deemed to be symptomatically stable by the clinical staff in the last two months
- Over 7% total body weight increase on antipsychotics for subjects within first year of illness
Who cannot join
- Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use.) Note: All subjects will be screened for drugs, not only those suspected of opiate use.
- A history of seizures in the past five years (confirmed through chart review and discussion with patient's clinician)
- Meet DSM criteria for Bipolar Disorder
- History of mania in the past one year (confirmed through chart review and discussion with patient's clinician)
- Uncontrolled hypertension
- Insulin dependent diabetes mellitus
Show all 12Show fewer
- Current history of dementia, mental retardation
- Not capable of giving informed consent for participation in the study
- Women who are pregnant or breast-feeding
- Physical conditions affecting body weight (e.g. Cushing's disease, polycystic ovary syndrome)
- Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.
- History of glaucoma.
Trial locations and contacts
1 site in 1 country.
United States1 site
Connecticut Mental Health Center
New Haven, Connecticut, 06519
About this study
Official title: A Pilot Trial of Naltrexone-Bupropion Combination Versus Placebo Combined With Bupropion for Weight Loss in Comorbid Schizophrenia
The purpose of this study is to determine the efficacy of combining open-label extended release bupropion (flexible dosing up to 450mg target) and naltrexone (37.5mg) versus Bupropion and placebo along with a daily 500 calorie reduction diet recommendation for weight and health risk reduction in 40 overweight/obese individuals with schizophrenia.
Read the detailed description
The combination of naltrexone with noradrenaline/dopamine reuptake blocker bupropion has been developed and FDA-approved for the treatment of obesity in the general population. Naltrexone does not normally produce weight loss in humans and bupropion produces modest weight loss, however the combination produces clinically significant weight loss, which appears to be more than the sum of its components would otherwise produce separately. Of interest to us, the combination has been shown to be effective for clinically significant weight loss in obese subjects with type 2 diabetes as well. Registration studies by the manufacturer of the combination pill excluded antipsychotic medication users, thus we have no information on the potential effectiveness of the combination in this population. Both naltrexone and bupropion are commonly used in psychiatry, naltrexone for co-morbid alcohol addiction, and bupropion for co-morbid depression and/or cigarette addiction. This is a 16-week pilot trial of 37.5mg naltrexone/placebo added to extended release bupropion in flexible dosing (150mg to 450mg) and a daily 500 calorie reduction diet recommendation for subjects with schizophrenia and obesity. A dose of 37.5mg is similar to the FDA-approved combination dose for naltrexone. However, based on our experience with bupropion, we have chosen to use bupropion in an un-blinded manner and reach the target dose of 450mg based on tolerance of the individual subject over the initial 3-week period.
Changes to the study since registration:
The study was initially registered with 3 arms (Naltrexone vs Bupropion vs Placebo)- whereas the original intent was always supposed to be a 2 armed study (Naltrexone vs Placebo- each with Bupropion included)- this was corrected when the results of the terminated study were entered. In addition, there was an initial intent to include diabetics in the study, but this was later removed as well.
- Conditions
- Schizophrenia, Diabetes Mellitus, Type 2, Obesity
- Being tested
- Naltrexone, Bupropion, Placebo
- Keywords
- Schizophrenia, Diabetes, Obesity
- Medical subject headings
- Schizophrenia, Diabetes Mellitus, Type 2, Obesity, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called Revia
37.mg oral capsule taken once daily for over the course of the study (16 weeks)
BupropionDrug
Also called Wellbutrin, Zyban
Extended release bupropion taken once daily for the course of the study (16 weeks) flexible dosing up to 450mg target.
PlaceboOther
Oral placebo taken once daily for the course of the study (16 week)
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone with Bupropion | Experimental | Oral Naltrexone taken once a day and Oral Bupropion taken once a day for 16 weeks. Receives: Drug: Naltrexone; Drug: Bupropion |
| Placebo with Bupropion | Placebo comparator | Oral placebo capsule and Oral Bupropion taken once a day for 16 weeks. Receives: Drug: Bupropion; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
BMI
BMI will be calculated using weekly height and weight measurements (kg/m^2) at each assessment.
Measured: Baseline and Week 16
Secondary outcomes (3)
Weight (kg)
Weight in kilograms will be measured at each assessment and change will be determined at study endpoint.
Measured: Baseline and Week 16
Health Risk Markers
Serum lipid profiles, fasting glucose, and glycosylated hemoglobin (hbA1c) will be measured at baseline and week 16 and change in these markers will be determined at endpoint
Measured: Baseline to Week 16
Waist Circumference (Inches)
Waist circumference will be measured in inches at each assessment.
Measured: Baseline and Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Apr 2017
- Study start1 Jun 2017
- Primary completion31 Jul 2018
- Study completion31 Jul 2018
Why it stopped: Study discontinued due to funding.
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.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Cenk Tek, MD, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03132571
- Sponsor's protocol ID
- 1606017928
- Acronym
- NBC
- Status last verified
- Aug 2019
- First submitted
- 17 Apr 2017
- Last updated
- 7 Aug 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All de-identified data resulting from this award involving human subjects will be submitted to the NIMH Data Archive (NDA) - National Database for Clinical Trials Related to Mental Illness (NDCT) The Principal Investigator will work with NDA support staff to plan an appropriate data submission schedule and provide information on the steps for submission and sharing of data. Communication of this data sharing plan to appropriate research staff to ensure the timely submission of data. All human subject data provided will include an NDA Global Unique Identifier (GUID) and will not include personally identifiable information (PII). Analyzed data will be submitted no later than the time of publication. Even if a publication focuses on only part of an analyzed dataset, the entire analyzed dataset will be submitted when the first paper is published. All data made available for public use via NDA will be de-identified data.
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Trial of Naltrexone-Bupropion Combination Versus Placebo Combined With Bupropion for Weight Loss in Comorbid Schizophrenia
- ClinicalTrials.gov ID
- NCT03132571
- Acronym / sponsor ID
- NBC / 1606017928
- Conditions
- Schizophrenia, Diabetes Mellitus, Type 2, Obesity
- Keywords
- Schizophrenia, Diabetes, Obesity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study discontinued due to funding.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- 1 Jun 2017 (actual)
- Primary completion
- 31 Jul 2018 (actual)
- Study completion
- 31 Jul 2018 (actual)
- First posted
- 28 Apr 2017 (actual)
- Results
- Posted 7 Aug 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the efficacy of combining open-label extended release bupropion (flexible dosing up to 450mg target) and naltrexone (37.5mg) versus Bupropion and placebo along with a daily 500 calorie reduction diet recommendation for weight and health risk reduction in 40 overweight/obese individuals with schizophrenia.
Detailed description
The combination of naltrexone with noradrenaline/dopamine reuptake blocker bupropion has been developed and FDA-approved for the treatment of obesity in the general population. Naltrexone does not normally produce weight loss in humans and bupropion produces modest weight loss, however the combination produces clinically significant weight loss, which appears to be more than the sum of its components would otherwise produce separately. Of interest to us, the combination has been shown to be effective for clinically significant weight loss in obese subjects with type 2 diabetes as well. Registration studies by the manufacturer of the combination pill excluded antipsychotic medication users, thus we have no information on the potential effectiveness of the combination in this population. Both naltrexone and bupropion are commonly used in psychiatry, naltrexone for co-morbid alcohol addiction, and bupropion for co-morbid depression and/or cigarette addiction. This is a 16-week pilot trial of 37.5mg naltrexone/placebo added to extended release bupropion in flexible dosing (150mg to 450mg) and a daily 500 calorie reduction diet recommendation for subjects with schizophrenia and obesity. A dose of 37.5mg is similar to the FDA-approved combination dose for naltrexone. However, based on our experience with bupropion, we have chosen to use bupropion in an un-blinded manner and reach the target dose of 450mg based on tolerance of the individual subject over the initial 3-week period.
Changes to the study since registration:
The study was initially registered with 3 arms (Naltrexone vs Bupropion vs Placebo)- whereas the original intent was always supposed to be a 2 armed study (Naltrexone vs Placebo- each with Bupropion included)- this was corrected when the results of the terminated study were entered. In addition, there was an initial intent to include diabetics in the study, but this was later removed as well.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Naltrexone with Bupropion | Experimental | Drug: Naltrexone, Drug: BupropionOral Naltrexone taken once a day and Oral Bupropion taken once a day for 16 weeks. |
| Placebo with Bupropion | Placebo comparator | Drug: Bupropion, Other: PlaceboOral placebo capsule and Oral Bupropion taken once a day for 16 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18 to 75
- Meet DSM-IV criteria for schizophrenia or schizoaffective disorder based on SCID interview (If bipolar-schizoaffective: need to be adequately stabilized on a mood stabilizer and show no mania history for the past one year, as confirmed by study psychiatrist and patient's clinician)
- Body Mass Index (BMI) of 28 and over
- On a stable dose of antipsychotic medication; i.e. at least one month with no dose change, and three months from an antipsychotic switch
- Deemed to be symptomatically stable by the clinical staff in the last two months
Key exclusion criteria (12 listed)
- Meet criteria for current opiate abuse or dependence (confirmed by positive urine drug screen for opiates or, if suspected by study doctor via patient history and or suspicion of occult opiate use.) Note: All subjects will be screened for drugs, not only those suspected of opiate use.
- A history of seizures in the past five years (confirmed through chart review and discussion with patient's clinician)
- Meet DSM criteria for Bipolar Disorder
- History of mania in the past one year (confirmed through chart review and discussion with patient's clinician)
- Uncontrolled hypertension
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 |
|---|---|---|
| NaltrexoneAlso: Revia37.mg oral capsule taken once daily for over the course of the study (16 weeks) | Drug | Naltrexone with Bupropion |
| BupropionAlso: Wellbutrin, ZybanExtended release bupropion taken once daily for the course of the study (16 weeks) flexible dosing up to 450mg target. | Drug | Naltrexone with Bupropion, Placebo with Bupropion |
| PlaceboOral placebo taken once daily for the course of the study (16 week) | Other | Placebo with Bupropion |
Primary outcome
BMI
Time frame: Baseline and Week 16
BMI will be calculated using weekly height and weight measurements (kg/m^2) at each assessment.
3 secondary outcomes
Weight (kg)
Time frame: Baseline and Week 16
Health Risk Markers
Time frame: Baseline to Week 16
Waist Circumference (Inches)
Time frame: Baseline and Week 16
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. All de-identified data resulting from this award involving human subjects will be submitted to the NIMH Data Archive (NDA) - National Database for Clinical Trials Related to Mental Illness (NDCT) The Principal Investigator will work with NDA support staff to plan an appropriate data submission schedule and provide information on the steps for submission and sharing of data. Communication of this data sharing plan to appropriate research staff to ensure the timely submission of data. All human subject data provided will include an NDA Global Unique Identifier (GUID) and will not include personally identifiable information (PII). Analyzed data will be submitted no later than the time of publication. Even if a publication focuses on only part of an analyzed dataset, the entire analyzed dataset will be submitted when the first paper is published. All data made available for public use via NDA will be de-identified data.
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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.
Cenk Tek, MD principal investigator
Yale University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naltrexone and Bupropion in people with Schizophrenia and Diabetes Mellitus, Type 2, run by Yale University 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 6 inclusion and 12 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: stopped early, as of the sponsor's last update on 7 Aug 2019. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Aug 2019). 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?
BMI (time frame: Baseline and Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 7 Aug 2019.