Healthy Volunteers Study of the Effects of Olanzapine and Ziprasidone

• ClinicalTrials.gov Identifier: NCT00910988
• Recruitment Status: Completed
• First Posted: June 1, 2009
• Results First Posted: January 15, 2014
• Last Update Posted: July 18, 2018
• Sponsor: Washington University School of Medicine
• Collaborator: Pfizer
• Information provided by (Responsible Party): Washington University School of Medicine

Study Description

Brief Summary:

Primary Aim: To test the acute effects of olanzapine or ziprasidone administration, in comparison to placebo, on insulin sensitivity in antipsychotic-naïve healthy young men, measured as whole-body dextrose infusion rates (mg/kg/min), hepatic glucose production (glucose rate of appearance [Ra]), primarily muscle glucose utilization (glucose rate of disappearance [Rd]), and adipose tissue related free fatty acid production (glycerol rate of appearance [Ra]).

We hypothesize that olanzapine, but not ziprasidone, will result in acute decreases in insulin sensitivity.

Secondary Aim: To test the acute effects of olanzapine or ziprasidone on insulin signaling pathways in antipsychotic naïve healthy young men.

We hypothesize that olanzapine, but not ziprasidone, will result in acute alterations in insulin signaling.

Condition or disease	Intervention/treatment	Phase
Hyperglycemia; Hyperlipidemia	Drug: Olanzapine; Drug: Ziprasidone	Not Applicable

Detailed Description:

See brief description

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: A Randomized Comparison of the Acute Effects of Olanzapine and Ziprasidone on Whole Body Insulin Sensitivity in Healthy Volunteers
• Study Start Date: February 2009
• Actual Primary Completion Date: June 2012
• Actual Study Completion Date: June 2012

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: olanzapine; olanzapine injection in healthy control	Drug: Olanzapine; olanzapine/Zyprexa; Other Name: Zyprexa
Active Comparator: ziprasidone; ziprasidone injection in healthy control	Drug: Ziprasidone; ziprasidone/Geodon; Other Name: Geodon
Placebo Comparator: saline; saline injection in healthy control	Drug: Olanzapine; olanzapine/Zyprexa; Other Name: Zyprexa; Drug: Ziprasidone; ziprasidone/Geodon; Other Name: Geodon

Outcome Measures

Primary Outcome Measures :

1. Whole Body Insulin Sensitivity [ Time Frame: approximately 3 hours ]
   To evaluate, using a within-subject placebo-controlled comparison, the acute effects of olanzapine or ziprasidone administration on insulin sensitivity in antipsychotic-naïve healthy young men, measured as whole-body dextrose infusion rates (mg/kg/min).
2. Hepatic Insulin Sensitivity [ Time Frame: approximately 3 hours ]
   To evaluate, using a within-subject placebo-controlled comparison, the acute effects of olanzapine or ziprasidone administration on insulin sensitivity in antipsychotic-naïve healthy young men, measured as hepatic glucose production (glucose rate of appearance [Ra]).
3. Peripheral Insulin Sensitivity [ Time Frame: approximately 3 hours ]
   To evaluate, using a within-subject placebo-controlled comparison, the acute effects of olanzapine or ziprasidone administration on insulin sensitivity in antipsychotic-naïve healthy young men, measured as primarily muscle glucose utilization (glucose rate of disappearance [Rd]).
4. Adipose Tissue Insulin Sensitivity [ Time Frame: approximately 3 hours ]
   To evaluate, using a within-subject placebo-controlled comparison, the acute effects of olanzapine or ziprasidone administration on insulin sensitivity in antipsychotic-naïve healthy young men, measured as free fatty acid release (glycerol rate of appearance [Ra]).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Males aged 18-45 years
• BMI approximately ≥ 25 and < 35
• insulin approximately ≥ 15 µU/ml or triglyceride approximately ≥ 130 mg/dl

Exclusion Criteria:

• Any DSM-IV Axis I diagnosis
• prisoners
• any serious medical disorder (i.e. metabolic diseases, type 1 or 2 diabetes mellitus, endocrine disease, coagulopathy, clinically significant anemia, acute infection)
• taking prescription medications
• non-sedentary lifestyle with > 3 hours of exercise per week

Contacts and Locations

Locations

United States, Missouri

Washington University School of Medicine

Saint Louis, Missouri, United States, 63110

Sponsors and Collaborators

Washington University School of Medicine

Pfizer

Investigators

• Principal Investigator: John W Newcomer, MD; Washington University School of Medicine and Florida Atlantic University
• Principal Investigator: Ginger Nicol, MD; Washington University School of Medicine

More Information

• Responsible Party: Washington University School of Medicine
• ClinicalTrials.gov Identifier: NCT00910988
• Other Study ID Numbers: 08-0540
• First Posted: June 1, 2009
• Results First Posted: January 15, 2014
• Last Update Posted: July 18, 2018
• Last Verified: June 2018

Keywords provided by Washington University School of Medicine:

healthy; sedentary; men; acute effects of antipsychotic; blood sugar; insulin sensitivity

Additional relevant MeSH terms:

Hyperglycemia; Hyperlipidemias; Glucose Metabolism Disorders; Metabolic Diseases; Dyslipidemias; Lipid Metabolism Disorders; Olanzapine; Ziprasidone; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Gastrointestinal Agents; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Agents; Serotonin Agents; Serotonin Antagonists; Dopamine Antagonists; Dopamine Agents