SchizophreniaPhase 1ZyprexaNCT00567034
Augmenting Zyprexa With Naltrexone to Ameliorate Metabolic Side-Effects
A Phase 1 study testing naltrexone in people with Schizophrenia and Psychotic Disorders, run by Mclean Hospital at 1 site in United States.
Trial summary
The main purpose of this study is to determine whether the opioid antagonist naltrexone is helpful in ameliorating the weight gain and other adverse metabolic side effects experienced by schizophrenic patients taking the second generation antipsychotic (SGA) Zyprexa. Read more about this study
- Who is it for?
- Ages 21 to 55 years
- Conditions the study is for
- Schizophrenia, Psychotic Disorders
- 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
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 21 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Meeting DSM-IV-TR criteria for schizophrenia/schizoaffective disorder, confirmed by clinical interview with PI and SCID-I.
- On a stable dose of Zyprexa (i.e., greater than or equal to 10mg/day and less than or equal to 30mg/day) for at least 2 months; patients on typical antipsychotics or in a medications-free state will be also included and used for baseline comparison.
- Sufficient clinical stability (i.e., BPRS psychotic symptoms score of less than 19; BPRS anxiety/depression symptoms score of less than 15).
- Participation approved by the treating psychiatrist.
- BMI greater than or equal to 30kg/m^2 or BMI greater than or equal to 27kg/m^2 plus one symptom of the "Metabolic Syndrome" (i.e., fasting blood sugar greater than 125mg/dL, hypertension or dyslipidemia).
- Sufficient social stability following study admission, such as having safe, reliable living quarters, telephone access and at least one living relative or significant other willing to assist the subject following discharge from the study and to assist the staff if necessary to locate the subject subsequently.
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- English speaking and reading ability sufficient to comprehend consent without assistance.
- Good physical health, no history of significant medical, surgical, or neurological illness, including any history of head trauma.
- Right-handedness
- Able to cooperate and comply with study procedures.
Who cannot join
- DSM-IV-TR diagnosis of current drug/alcohol dependence.
- Any lifetime history of dementia, bipolar disorder, major depression, other psychotic disorder, past or current drug/alcohol dependence, past or current eating disorder.
- Potentially confounding neurological condition (e.g., seizure disorder, head trauma accompanied by loss of consciousness greater than ten minutes or amnesia, brain surgery, multiple sclerosis, Parkinson's disease), or potentially confounding medical condition (e.g., diabetes mellitus or other endocrinopathy, chronic obstructive pulmonary disease, congestive heart failure, hepatitis, hepatic failure or cirrhosis, AIDS, pacemaker, kidney problems, hypokalemia, edema, and allergy to glucose).
- Allergy or hypersensitivity to naltrexone
- Abnormal laboratory, ECG or EEG results, elevated serum aminotransferases.
- Use within the previous month of any potentially confounding medications such as opioid agonists (e.g., morphine or codeine) or drugs with prominent orexigenic/anorexigenic effects (e.g., anticholinergics), insulin, oral hypoglycemics, amphetamines, opioid analgesics, anti-depressants including tricyclics, MAO inhibitors or mirtazapine, as determined by history and/or urine toxicology screen.
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- Patient is pregnant or planning on becoming pregnant.
- Any cognitive impairment that precludes informed consent.
- Any chronic pain condition and/or any condition that may require opioid treatment in the course of the study.
- Dangerousness: any suicidal, assaultive or homicidal risks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Augmenting Zyprexa With Naltrexone: Normalization of the Weight Gain Side Effect and the CNS Reward and Sensory Function
The main purpose of this study is to determine whether the opioid antagonist naltrexone is helpful in ameliorating the weight gain and other adverse metabolic side effects experienced by schizophrenic patients taking the second generation antipsychotic (SGA) Zyprexa. Schizophrenics may have an altered/enhanced endogenous opioidergic drive, and because of this, normally painful stimuli will be sensed as less painful in schizophrenics vs. healthy controls. A secondary hypothesis for this study is that naltrexone augmentation of Zyprexa will normalize subjective pain ratings. Our tertiary objective is to examine the safety and tolerability of naltrexone in Zyprexa-treated patients with schizophrenia.
Read the detailed description
Zyprexa is one of the most commonly prescribed second generation antipsychotic drugs (SGAs), but its (and other SGA's) side effects contribute to the development of obesity and to the "Metabolic Syndrome." Both conditions, which are more prevalent even in unmedicated schizophrenic patients, are associated with increased cardiovascular morbidity and mortality. The mechanisms of these side effects are likely to be multifactorial and to involve peripheral and central factors alike. The present proposal asks a fundamental question: How the endogenous opioidergic systems are involved in Zyprexa-induced obesity and in related metabolic disturbances. We further hypothesize that if the excess of central opioid activity creates metabolic problems for patients, it is reasonable to expect amelioration of the symptoms through blockade of opioid receptors. The proposed project is designed to test this hypothesis by complimenting clinical psychopharmacology with pain medicine research and functional magnetic resonance imaging (fMRI) to empirically measure clinical outcomes of Zyprexa pharmacotherapy augmentation with the opioid receptor antagonist, naltrexone. Our objectives and hypotheses are as follows: to determine the effects of naltrexone on weight gain, metabolic (e.g., cholesterol, lipids, insulin, leptin and glucose levels), anthropometric and nutritional characteristics in Zyprexa treated schizophrenic patients, to examine the effects of naltrexone on subjective pain ratings, and to investigate the safety and tolerability of naltrexone in Zyprexa-treated schizophrenic patients.
- Conditions
- Schizophrenia, Psychotic Disorders
- Being tested
- naltrexone, placebo
- Keywords
- Zyprexa, naltrexone, schizophrenia, Metabolic Syndrome, pain
- Medical subject headings
- Schizophrenia, Psychotic Disorders, Metabolic Syndrome, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
naltrexoneDrug
50mg naltrexone, 1 tablet a day for 12 weeks.
placeboDrug
lactose placebo, 1 capsule every day for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Active comparator | taking naltrexone Receives: Drug: naltrexone |
| 2 | Placebo comparator | taking placebo Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight and Body Mass Index
Measured: 12 weeks
Secondary outcomes (1)
Subjective pain ratings, fMRI activations in the a priori selected ROIs, waist, waist/hip ratio, fasting blood glucose, LDL cholesterol, HDL cholesterol, triglycerides, fat body mass, insulin, leptin, and food intake
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 posted4 Dec 2007 (estimated)
- Study startDec 2006
- Primary completionDec 2010
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies 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 1
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Igor Elman, MD, Mclean Hospital
- Investigators
- Igor Elman, M.D., Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00567034
- Sponsor's protocol ID
- 2006-P-0002381/3
- Other IDs
- F1D-US-X306
- Acronym
- Zyprexa
- Status last verified
- Oct 2013
- First submitted
- 3 Dec 2007
- Last updated
- 25 Oct 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Augmenting Zyprexa With Naltrexone: Normalization of the Weight Gain Side Effect and the CNS Reward and Sensory Function
- ClinicalTrials.gov ID
- NCT00567034
- Acronym / sponsor ID
- Zyprexa / 2006-P-0002381/3
- Conditions
- Schizophrenia, Psychotic Disorders
- Keywords
- Zyprexa, naltrexone, schizophrenia, Metabolic Syndrome, pain
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Study start
- Dec 2006
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 4 Dec 2007 (estimated)
- 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.
The main purpose of this study is to determine whether the opioid antagonist naltrexone is helpful in ameliorating the weight gain and other adverse metabolic side effects experienced by schizophrenic patients taking the second generation antipsychotic (SGA) Zyprexa. Schizophrenics may have an altered/enhanced endogenous opioidergic drive, and because of this, normally painful stimuli will be sensed as less painful in schizophrenics vs. healthy controls. A secondary hypothesis for this study is that naltrexone augmentation of Zyprexa will normalize subjective pain ratings. Our tertiary objective is to examine the safety and tolerability of naltrexone in Zyprexa-treated patients with schizophrenia.
Detailed description
Zyprexa is one of the most commonly prescribed second generation antipsychotic drugs (SGAs), but its (and other SGA's) side effects contribute to the development of obesity and to the "Metabolic Syndrome." Both conditions, which are more prevalent even in unmedicated schizophrenic patients, are associated with increased cardiovascular morbidity and mortality. The mechanisms of these side effects are likely to be multifactorial and to involve peripheral and central factors alike. The present proposal asks a fundamental question: How the endogenous opioidergic systems are involved in Zyprexa-induced obesity and in related metabolic disturbances. We further hypothesize that if the excess of central opioid activity creates metabolic problems for patients, it is reasonable to expect amelioration of the symptoms through blockade of opioid receptors. The proposed project is designed to test this hypothesis by complimenting clinical psychopharmacology with pain medicine research and functional magnetic resonance imaging (fMRI) to empirically measure clinical outcomes of Zyprexa pharmacotherapy augmentation with the opioid receptor antagonist, naltrexone. Our objectives and hypotheses are as follows: to determine the effects of naltrexone on weight gain, metabolic (e.g., cholesterol, lipids, insulin, leptin and glucose levels), anthropometric and nutritional characteristics in Zyprexa treated schizophrenic patients, to examine the effects of naltrexone on subjective pain ratings, and to investigate the safety and tolerability of naltrexone in Zyprexa-treated schizophrenic patients.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Active comparator | Drug: naltrexonetaking naltrexone |
| 2 | Placebo comparator | Drug: placebotaking placebo |
Who may qualify
- Ages
- 21 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Meeting DSM-IV-TR criteria for schizophrenia/schizoaffective disorder, confirmed by clinical interview with PI and SCID-I.
- On a stable dose of Zyprexa (i.e., greater than or equal to 10mg/day and less than or equal to 30mg/day) for at least 2 months; patients on typical antipsychotics or in a medications-free state will be also included and used for baseline comparison.
- Sufficient clinical stability (i.e., BPRS psychotic symptoms score of less than 19; BPRS anxiety/depression symptoms score of less than 15).
- Participation approved by the treating psychiatrist.
- BMI greater than or equal to 30kg/m^2 or BMI greater than or equal to 27kg/m^2 plus one symptom of the "Metabolic Syndrome" (i.e., fasting blood sugar greater than 125mg/dL, hypertension or dyslipidemia).
Key exclusion criteria (10 listed)
- DSM-IV-TR diagnosis of current drug/alcohol dependence.
- Any lifetime history of dementia, bipolar disorder, major depression, other psychotic disorder, past or current drug/alcohol dependence, past or current eating disorder.
- Potentially confounding neurological condition (e.g., seizure disorder, head trauma accompanied by loss of consciousness greater than ten minutes or amnesia, brain surgery, multiple sclerosis, Parkinson's disease), or potentially confounding medical condition (e.g., diabetes mellitus or other endocrinopathy, chronic obstructive pulmonary disease, congestive heart failure, hepatitis, hepatic failure or cirrhosis, AIDS, pacemaker, kidney problems, hypokalemia, edema, and allergy to glucose).
- Allergy or hypersensitivity to naltrexone
- Abnormal laboratory, ECG or EEG results, elevated serum aminotransferases.
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 |
|---|---|---|
| naltrexone50mg naltrexone, 1 tablet a day for 12 weeks. | Drug | 1 |
| placebolactose placebo, 1 capsule every day for 12 weeks | Drug | 2 |
Primary outcome
Weight and Body Mass Index
Time frame: 12 weeks
1 secondary outcome
Subjective pain ratings, fMRI activations in the a priori selected ROIs, waist, waist/hip ratio, fasting blood glucose, LDL cholesterol, HDL cholesterol, triglycerides, fat body mass, insulin, leptin, and food intake
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2013.
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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.
Igor Elman, M.D. principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing naltrexone in people with Schizophrenia and Psychotic Disorders, run by Mclean Hospital 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 10 inclusion and 10 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 25 Oct 2013. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Weight and Body Mass Index (time frame: 12 weeks). 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 25 Oct 2013.