SchizophreniaNTXNCT01866098
Naltrexone for Antipsychotic-Induced Weight Gain
A study testing Naltrexone in people with Schizophrenia and Schizoaffective Disorder, run by Yale University at 1 site in United States.
Trial summary
This study is designed to look at the effects of naltrexone on weight loss in individuals treated with antipsychotic medications. Naltrexone is an FDA approved medication for the management of alcohol dependence and drug dependence, but has not been fully evaluated for its effect on weight loss in individuals with… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder
- What is being tested?
- Naltrexone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to 7 Apr 2019
- Phase
- Interventional
- 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 Diagnostic \& Statistical Manual - 4 (DSM-IV) criteria for schizophrenia, schizoaffective disorder, bipolar disorder, major depression, or another psychotic disorder based on Structured Clinical Interview for the DSM-IV (SCID) interview
- 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, a naloxone challenge will be performed.)
- 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) Diabetes Mellitus (defined as prescribed an anti-diabetic medication for diabetes or a hemoglobin A1c level > 7 confirmed by primary care physician at screening)
- Severe liver dysfunction, (serum aminotransferases greater than three times normal), acute infectious hepatitis, liver failure.
Trial locations and contacts
1 site in 1 country.
United States1 site
Connecticut Mental Health Center
New Haven, Connecticut, 06519
About this study
This study is designed to look at the effects of naltrexone on weight loss in individuals treated with antipsychotic medications. Naltrexone is an FDA approved medication for the management of alcohol dependence and drug dependence, but has not been fully evaluated for its effect on weight loss in individuals with severe mental illness (i.e. schizophrenia, schizoaffective disorder, bipolar disorder etc.) The purpose of this study is to find out how effective two different doses of oral naltrexone is on reducing body weight when compared to placebo (an inactive substance or "sugar pill").
Read the detailed description
Persons with severe mental illness (SMI) die, on average, 25 years earlier than the general population1. Most of this early mortality can be attributed to cardiovascular disease (CVD) and diabetes mellitus (DM), which are directly related to obesity. Obesity is a leading cause of preventable death in the United States, second only to smoking. The physical health of patients has become a major focus of schizophrenia care, as recent decades have seen immense gains in symptom control and community integration. There is an urgent need for the development of interventions that address the obesity crisis in schizophrenia.
Patients treated with antipsychotic medications have been shown to have a preference for diets high in fat and sugar. Patients with schizophrenia typically seek behaviors that increase dopamine mediated reward in the brain such as smoking and substance use, both of which occur more often in this group than the general population. The system might require intact dopamine and opioid function.
Naltrexone is an oral agent that competitively antagonizes all known opioid receptors in the brain. Human studies with naltrexone were completed in individuals with different illnesses, including schizophrenia, and have been shown to be a safe and easy agent to use. It is shown to decrease craving in alcoholics and is approved by the FDA for the treatment of alcohol dependence. Naltrexone is reported to decrease craving for other substances of abuse, like nicotine. Furthermore, it has been shown to prevent secondary weight gain due to cessation of cigarette smoking at low (25mg and 50 mg), but not higher doses. Naltrexone has been tested in human feeding studies, and has been shown to reduce both the quantity of food eaten and the choice of palatable foods.
Subjects will be randomized to either 25, 50 or 0mg of Naltrexone and will take the study medication daily for 52 weeks. Subjects will be seen weekly for the first 4 weeks of the study, thereafter they will be seen on a bi-weekly (every other week) basis to be assessed (i.e. weight, side effect check, paper questionnaires) throughout the remaining 48 weeks of treatment.
The purpose of this study is to determine the efficacy of two doses of naltrexone (25mg \& 50mg) versus placebo for weight and health risk reduction in 144 obese individuals with severe mental illness treated with an antipsychotic medication.
- Conditions
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Bipolar Disorder, Severe Major Depression With Psychotic Features
- Being tested
- Naltrexone, Placebo
- Keywords
- antipsychotic, severe mental illness, weight loss
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Bipolar Disorder, Mental Disorders, Weight Loss
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NaltrexoneDrug
Also called Revia
25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Naltrexone 50mg | Experimental | Oral Naltrexone 50mg capsule taken once daily for 52 weeks Receives: Drug: Naltrexone |
| Placebo | Placebo comparator | Oral placebo capsule taken once daily for 52 weeks Receives: Drug: Placebo |
| Naltrexone 25mg | Experimental | Oral Naltrexone 25mg capsule taken once daily for 52 weeks Receives: Drug: Naltrexone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Weight From Baseline
Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.
Measured: Baseline and 52 weeks
Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline
Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.
Measured: 52 weeks
Secondary outcomes (6)
Changes in Fasting Glucose From Baseline
Fasting glucose will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Changes in Glycosylated Hemoglobin (HbA1c) From Baseline
Glycosylated hemoglobin (HbA1c) will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Changes in Insulin From Baseline
Insulin will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Changes in Total Cholesterol From Baseline
Total Cholesterol will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Changes in HDL From Baseline
High-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Changes in LDL From Baseline
Low-density lipoprotein (HDL) will be collected over the course of participation and changes will be evaluated at study endpoint.
Measured: Baseline and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2013 (estimated)
- Study startMay 2013
- Primary completion7 Apr 2019
- Study completion7 Apr 2019
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 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 144 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
- NCT01866098
- Sponsor's protocol ID
- 1207010507
- Other IDs
- 1R01DK093924-01A1
- Acronym
- NTX
- Status last verified
- Sep 2021
- First submitted
- 12 Mar 2013
- Last updated
- 1 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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.
Publications
Tek C, Guloksuz S, Srihari VH, Reutenauer EL. Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial. BMC Psychiatry. 2013 Jun 27;13:176. doi: 10.1186/1471-244X-13-176.
PubMed 23805859
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naltrexone for Antipsychotic-Induced Weight Gain
- ClinicalTrials.gov ID
- NCT01866098
- Acronym / sponsor ID
- NTX / 1207010507
- Conditions
- Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder, Bipolar Disorder, Severe Major Depression With Psychotic Features
- Keywords
- antipsychotic, severe mental illness, weight loss
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- May 2013
- Primary completion
- 7 Apr 2019 (actual)
- Study completion
- 7 Apr 2019 (actual)
- First posted
- 31 May 2013 (estimated)
- Results
- Posted 8 Apr 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to look at the effects of naltrexone on weight loss in individuals treated with antipsychotic medications. Naltrexone is an FDA approved medication for the management of alcohol dependence and drug dependence, but has not been fully evaluated for its effect on weight loss in individuals with severe mental illness (i.e. schizophrenia, schizoaffective disorder, bipolar disorder etc.) The purpose of this study is to find out how effective two different doses of oral naltrexone is on reducing body weight when compared to placebo (an inactive substance or "sugar pill").
Detailed description
Persons with severe mental illness (SMI) die, on average, 25 years earlier than the general population1. Most of this early mortality can be attributed to cardiovascular disease (CVD) and diabetes mellitus (DM), which are directly related to obesity. Obesity is a leading cause of preventable death in the United States, second only to smoking. The physical health of patients has become a major focus of schizophrenia care, as recent decades have seen immense gains in symptom control and community integration. There is an urgent need for the development of interventions that address the obesity crisis in schizophrenia.
Patients treated with antipsychotic medications have been shown to have a preference for diets high in fat and sugar. Patients with schizophrenia typically seek behaviors that increase dopamine mediated reward in the brain such as smoking and substance use, both of which occur more often in this group than the general population. The system might require intact dopamine and opioid function.
Naltrexone is an oral agent that competitively antagonizes all known opioid receptors in the brain. Human studies with naltrexone were completed in individuals with different illnesses, including schizophrenia, and have been shown to be a safe and easy agent to use. It is shown to decrease craving in alcoholics and is approved by the FDA for the treatment of alcohol dependence. Naltrexone is reported to decrease craving for other substances of abuse, like nicotine. Furthermore, it has been shown to prevent secondary weight gain due to cessation of cigarette smoking at low (25mg and 50 mg), but not higher doses. Naltrexone has been tested in human feeding studies, and has been shown to reduce both the quantity of food eaten and the choice of palatable foods.
Subjects will be randomized to either 25, 50 or 0mg of Naltrexone and will take the study medication daily for 52 weeks. Subjects will be seen weekly for the first 4 weeks of the study, thereafter they will be seen on a bi-weekly (every other week) basis to be assessed (i.e. weight, side effect check, paper questionnaires) throughout the remaining 48 weeks of treatment.
The purpose of this study is to determine the efficacy of two doses of naltrexone (25mg \& 50mg) versus placebo for weight and health risk reduction in 144 obese individuals with severe mental illness treated with an antipsychotic medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Naltrexone 50mg | Experimental | Drug: NaltrexoneOral Naltrexone 50mg capsule taken once daily for 52 weeks |
| Placebo | Placebo comparator | Drug: PlaceboOral placebo capsule taken once daily for 52 weeks |
| Naltrexone 25mg | Experimental | Drug: NaltrexoneOral Naltrexone 25mg capsule taken once daily for 52 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 Diagnostic \& Statistical Manual - 4 (DSM-IV) criteria for schizophrenia, schizoaffective disorder, bipolar disorder, major depression, or another psychotic disorder based on Structured Clinical Interview for the DSM-IV (SCID) interview
- 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 (6 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, a naloxone challenge will be performed.)
- 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) Diabetes Mellitus (defined as prescribed an anti-diabetic medication for diabetes or a hemoglobin A1c level > 7 confirmed by primary care physician at screening)
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: Revia25 or 50mg (randomized) oral capsule taken once daily for 52 weeks to establish optimal dose for weight loss over the course of the study. | Drug | Naltrexone 25mg, Naltrexone 50mg |
| Placebo | Drug | Placebo |
Primary outcome
Change in Weight From Baseline
Time frame: Baseline and 52 weeks
Weight (kilograms; kg) will be measured at each assessment and change in weight will be determined at study endpoint.
Percent of Subjects Who Lost More Than 5% of Body Weight From Baseline
Time frame: 52 weeks
Body Mass Index will be calculated at each assessment and change over time will be assessed at endpoint.
6 secondary outcomes
Changes in Fasting Glucose From Baseline
Time frame: Baseline and 52 weeks
Changes in Glycosylated Hemoglobin (HbA1c) From Baseline
Time frame: Baseline and 52 weeks
Changes in Insulin From Baseline
Time frame: Baseline and 52 weeks
Changes in Total Cholesterol From Baseline
Time frame: Baseline and 52 weeks
Changes in HDL From Baseline
Time frame: Baseline and 52 weeks
Changes in LDL From Baseline
Time frame: Baseline and 52 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23805859Tek C, Guloksuz S, Srihari VH, Reutenauer EL. Investigating the safety and efficacy of naltrexone for anti-psychotic induced weight gain in severe mental illness: study protocol of a double-blind, randomized, placebo-controlled trial. BMC Psychiatry. 2013 Jun 27;13:176. doi: 10.1186/1471-244X-13-176.
- 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 study testing Naltrexone in people with Schizophrenia and Schizoaffective Disorder, 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 6 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 1 Oct 2021. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Apr 2020). 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?
Change in Weight From Baseline (time frame: Baseline and 52 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 NCT01866098, 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 1 Oct 2021.