Acute Impact of Intramuscular (IM) Aripiprazole and Olanzapine on Insulin Resistance in High Risk Prediabetics

NCT ID: NCT01411930

Last Updated: 2012-12-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-03-31
• Study Completion Date: 2011-08-31

Brief Summary

Antipsychotic medicines used to treat mental illnesses have been associated with effects on blood sugar control. Laboratory studies have shown that certain medications in particular may alter how insulin works. One purpose of this study is determine if antipsychotic medications have immediate effects on insulin action in individuals who do not have a mental disorder, but who have risk factors for diabetes. A second purpose is to demonstrate the feasibility of using volunteers without psychiatric disorders, and who do not take psychiatric medications, as a means for studying antipsychotic metabolic effects.

Detailed Description

Antipsychotic medications are those that treat the most severe psychiatric symptoms, such as hallucinations, paranoid thoughts, and delusions. Research shows that some of these medications may put people at a higher risk of metabolic derangements, such as insulin resistance. Certain antipsychotics, like clozapine and olanzapine, are associated with a higher risk of metabolic side effects than others, like aripiprazole and ziprasidone. This study will compare the effects of single doses of two antipsychotic medications, olanzapine and aripiprazole, on insulin action in nonpsychiatrically ill volunteer subjects.

Participation in this study will last 6 weeks. Participants will first complete a screening visit that will include the following: an oral glucose tolerance test (OGTT), which involves a blood draw, consumption of a sugar drink, and then a second blood draw; a review of medical and psychiatric history, including use of medicines and psychiatric medications; and measurement of participants' height and weight. The second visit, scheduled 2 weeks after screening, will include a tracer-clamp study to test how participants' bodies handle sugar. The tracer-clamp study will be conducted over the course of one night and morning and will require participants to stay at the study location overnight. At 3 AM, participants will receive an intravenous line (IV) with a sugar solution. Just before 8 AM, they will receive a second IV in the opposite arm that will draw blood and monitor blood sugar levels.

At 8 AM, participants will begin receiving insulin in the first IV; blood samples will be drawn and blood sugar levels will be monitored during this time to ensure they remain within a healthy range. At 11 AM, participants will receive an injection of an antipsychotic medication into their arm muscles. The antipsychotic, which will be randomly assigned, will be either olanzapine or aripiprazole. Participants will be monitored for 3 hours after receiving the injection of antipsychotic medication; during this time, more blood samples will be drawn, blood sugar levels will be monitored to ensure they are within a healthy range, and secondary medications will be available to counteract certain side effects of the antipsychotics.

After 4 more weeks, participants will undergo a 2nd tracer-clamp study, this time receiving the antipsychotic not given in the first clamp study. The protocol for this visit is otherwise identical to the first clamp study.

Conditions

Diabetes

Keywords

Insulin resistance; Antipsychotics; Olanzapine; Aripiprazole

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Olanzapine -> Aripiprazole

Crossover design. Order of agents is randomized. For this arm, the order will be IM olanzapine (1st clamp study) and IM aripiprazole (2nd clamp study).

Group Type: EXPERIMENTAL

Intramuscular olanzapine, aripiprazole

Intervention Type: DRUG

1. 1st clamp: single intramuscular 10.0 mg dose of olanzapine

2. 2nd clamp: single intramuscular 9.75 mg dose of aripiprazole

Aripiprazole -> Olanzapine

Crossover design. Order of agents is randomized. For this arm, the order will be IM aripiprazole (1st clamp study) and IM olanzapine (2nd clamp study).

Group Type: EXPERIMENTAL

Intramuscular aripiprazole, olanzapine

Intervention Type: DRUG

1. 1st clamp: single intramuscular 9.75 mg dose of aripiprazole

2. 2nd clamp: single intramuscular 10.0 mg dose of olanzapine

Interventions

Intramuscular olanzapine, aripiprazole

1. 1st clamp: single intramuscular 10.0 mg dose of olanzapine

2. 2nd clamp: single intramuscular 9.75 mg dose of aripiprazole

Intervention Type: DRUG

Intramuscular aripiprazole, olanzapine

1. 1st clamp: single intramuscular 9.75 mg dose of aripiprazole

2. 2nd clamp: single intramuscular 10.0 mg dose of olanzapine

Intervention Type: DRUG

Other Intervention Names

Olanzapine -> Aripiprazole; Aripiprazole -> Olanzapine

Eligibility Criteria

Inclusion Criteria

• No history of axis I mood, anxiety or psychotic disorder (confirmed by Structured Clinical Interview for DSM-IV), and taking no psychotropics
• Prediabetic, based on a finding of impaired glucose tolerance (2 hour post-load serum glucose 140-199 mg/dl) on a 75 gram standard oral glucose tolerance test within the past 90 days
• Family history of type 2 diabetes mellitus
• BMI 25-35 kg/m2
• Males, ages 40-65 inclusive
• English speaker with ability to provide informed consent
• Nonsmoker

Exclusion Criteria

• History of Axis I Mood, Anxiety or Psychotic Disorder or Use of Psychotropics

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

Veterans Medical Research Foundation

OTHER

Sponsor Role: lead

Responsible Party

Jonathan M. Meyer, MD

Research Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan M Meyer, MD

Role: PRINCIPAL_INVESTIGATOR

VA San Diego and VMRF

Locations

VA San Diego Healthcare System

San Diego, California, United States

Countries

United States

Other Identifiers

080225

Identifier Type: -

Identifier Source: org_study_id