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

Diabetes Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01411930
• Other study ID #: 080225
• Status: Completed
• Phase: Phase 4
• First received: September 15, 2009
• Last updated: December 19, 2012
• Start date: March 2009
• Est. completion date: August 2011

Study information

• Verified date: December 2012
• Source: Veterans Medical Research Foundation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 2011
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes
• Insulin Resistance

Intervention

Drug:
• Intramuscular olanzapine, aripiprazole
1st clamp: single intramuscular 10.0 mg dose of olanzapine 2nd clamp: single intramuscular 9.75 mg dose of aripiprazole
• Intramuscular aripiprazole, olanzapine
1st clamp: single intramuscular 9.75 mg dose of aripiprazole 2nd clamp: single intramuscular 10.0 mg dose of olanzapine

Locations

Country	Name	City	State
United States	VA San Diego Healthcare System	San Diego	California

Sponsors (2)

Lead Sponsor	Collaborator
Veterans Medical Research Foundation	Bristol-Myers Squibb

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Insulin sensitivity	2 overnight procedures 4 weeks apart, plus screening procedure	6 weeks	Yes
Secondary	Hepatic glucose production	2 overnight procedures 4 weeks apart, plus screening procedure	6 weeks	Yes