- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00567034
Augmenting Zyprexa With Naltrexone to Ameliorate Metabolic Side-Effects (Zyprexa)
October 24, 2013 updated by: Igor Elman, MD, Mclean Hospital
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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 Type
Interventional
Enrollment (Actual)
30
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Massachusetts
-
Belmont, Massachusetts, United States, 02478
- McLean Hospital
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
21 years to 55 years (Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: 1
taking naltrexone
|
50mg naltrexone, 1 tablet a day for 12 weeks.
|
Placebo Comparator: 2
taking placebo
|
lactose placebo, 1 capsule every day for 12 weeks
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Weight and Body Mass Index
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
|
12 weeks
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Igor Elman, M.D., McLean Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2006
Primary Completion (Actual)
December 1, 2010
Study Completion (Actual)
December 1, 2011
Study Registration Dates
First Submitted
December 3, 2007
First Submitted That Met QC Criteria
December 3, 2007
First Posted (Estimate)
December 4, 2007
Study Record Updates
Last Update Posted (Estimate)
October 25, 2013
Last Update Submitted That Met QC Criteria
October 24, 2013
Last Verified
October 1, 2013
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2006-P-0002381/3
- F1D-US-X306
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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