Effect of Short Term Atypical Antipsychotic Administration Compared to Placebo on Hepatic Insulin Extraction

NCT02447835 | Completed Phase 1

• 1 other identifier: 815905
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Within the past 20 years, there has been a striking increase in the incidence of obesity 1;2, type 2 diabetes mellitus (T2DM) 3-5, and cardiovascular diseases (CVD) in the schizophrenic population 6-8 . Large NIH-funded trials indicate that the prevalence of metabolic syndrome is twice to three times greater in schizophrenic patients on a specific class of drug termed the "atypical antipsychotics" (AAPs), of which olanzapine is an example, as compared to matched controls 8. Identification of the pathophysiological mechanisms contributing to metabolic disease in schizophrenic patients on AAPs has been hampered by the inability to differentiate underlying disease from treatment-emergent complications. In addition, despite falling within the same drug class, different AAPs exhibit differential associations with metabolic disease. Olanzapine is one of the AAPs associated with the greatest weight gain and degree of metabolic impairments.

Conditions

Normal Non-fluency

Keywords

Metabolic Disorders

Outcome Measures

Primary Outcomes (1)

• Determine the vagal contribution to the olanzapine-induced increase in circulating insulin levels.

  12 days

Secondary Outcomes (1)

• Determine if olanzapine increases meal-related/satiety peptides

  12 days

Study Arms (2)

Olanzapine

ACTIVE COMPARATOR

Olanzapine administration

Drug: Olanzapine

Placebo

PLACEBO COMPARATOR

Placebo administration

Drug: Olanzapine

Interventions

Olanzapine DRUG

Olanzapine is approved for the treatment of schizophrenia and mania associated with bipolar disorder. Olanzapine is a psychotropic agent that belongs to the thienobenzodiazepine class. The chemical designation is 2-methyl-4-4methyl-1 piperazinyl-10H-thienol (2,3-b)\[1,5\]benzodiazepine. The molecular formula is C17H20N4S which corresponds to a molecular weight of 312.44.Olanzpine is a yellow crystalline solid which is practically insoluble in water. Olanzapine is a selective monoaminergic antagonist with high affinity binding to the following receptors:5HT2A2C, 5HT6, dopamine 2-4, histamine H1, and adrenergic α-1. In addition olanzapine is an antagonist with moderate affinity for muscarinic M1-5 and 5HT3. The mechanism of action of olanzapine is unknown although it may be mediated through a combination of dopamine and serotonergic type 2 receptors.

Also known as: Zyprexa

Olanzapine; Placebo

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women ages 18-40
• BMI 19-24.5kg/m2
• Systolic BP \<130mm Hg
• Diastolic BP \<85mm Hg
• Subjects capable of giving informed consent, with no past or present psychiatric history
• Only women on oral contraceptives with constant dosing regimens or Depo-Provera for \>3 months, to ensure uniform hormonal delivery throughout the study duration
• No medications except as above noted
• Weight stable
• Minimal exercise regime that includes walking, running or biking

You may not qualify if:

• History of heart disease, colitis, autonomic neuropathy, hepatic or renal disease
• DSM-IV diagnosis of past or present psychiatric history, including clinically significant depression
• Drug/Alcohol dependence, homelessness, or inability to give informed consent
• History of asthma, congenital obstructive bladder, peptic ulcer, vasomotor instability, epilepsy, Parkinsonism, elevated thyroid hormone levels
• Diagnosis of diabetes
• BMI\>25 kg/m2
• Prescription medication (excluding the contraceptive methods described above)
• Hemoglobin \<11
• Abnormal laboratory tests which are clinically significant per the investigator
• Females pregnant or lactating
• Females: not taking hormonal contraceptives; taking hormonal contraceptives of varying dosage throughout the month
• Currently on a weight loss diet
• Moderate to significant exercise regime that includes swimming, weight lifting or other form of exercise not reproducible within CTRC.

Sponsors & Collaborators

• Michael Rickels: lead
• University of Pennsylvania: collaborator

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Metabolic Diseases

Interventions

Olanzapine

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine, University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes & Metabolism

Study Record Dates

• First Submitted: October 25, 2012
• First Posted: May 19, 2015
• Study Start: August 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: May 19, 2015

Record last verified: 2015-05

Locations

US (1)