Augmenting Zyprexa With Naltrexone to Ameliorate Metabolic Side-Effects

NCT00567034 | Completed Phase 1

• 2 other identifiers: 2006-P-0002381/3F1D-US-X306
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Schizophrenia; Psychotic Disorders

Keywords

Zyprexa; naltrexone; schizophrenia; Metabolic Syndrome; pain

Outcome Measures

Primary Outcomes (1)

• Weight and Body Mass Index

  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

  12 weeks

Study Arms (2)

1

ACTIVE COMPARATOR

taking naltrexone

Drug: naltrexone

2

PLACEBO COMPARATOR

taking placebo

Drug: placebo

Interventions

naltrexone DRUG

50mg naltrexone, 1 tablet a day for 12 weeks.

1

placebo DRUG

lactose placebo, 1 capsule every day for 12 weeks

2

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Mclean Hospital: lead

Study Sites (1)

McLean Hospital

Belmont, Massachusetts, 02478, United States

Location

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Metabolic Syndrome; Pain

Interventions

Naltrexone

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Igor Elman, M.D.

  Mclean Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: December 3, 2007
• First Posted: December 4, 2007
• Study Start: December 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2011
• Last Updated: October 25, 2013

Record last verified: 2013-10

Locations

US (1)