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

This study has been completed.
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
Jonathan M. Meyer, MD, Veterans Medical Research Foundation
ClinicalTrials.gov Identifier:
NCT01411930
First received: September 15, 2009
Last updated: December 19, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Diabetes
Drug: Intramuscular olanzapine, aripiprazole
Drug: Intramuscular aripiprazole, olanzapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Acute Impact of IM Aripiprazole and Olanzapine on Insulin Resistance in High Risk Prediabetics

Resource links provided by NLM:


Further study details as provided by Veterans Medical Research Foundation:

Primary Outcome Measures:
  • Insulin sensitivity [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    2 overnight procedures 4 weeks apart, plus screening procedure


Secondary Outcome Measures:
  • Hepatic glucose production [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    2 overnight procedures 4 weeks apart, plus screening procedure


Enrollment: 15
Study Start Date: March 2009
Study Completion Date: August 2011
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
Drug: 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
Other Name: Olanzapine -> Aripiprazole
Experimental: 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).
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
Other Name: Aripiprazole -> Olanzapine

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.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01411930

Locations
United States, California
VA San Diego Healthcare System
San Diego, California, United States, 92161
Sponsors and Collaborators
Veterans Medical Research Foundation
Bristol-Myers Squibb
Investigators
Principal Investigator: Jonathan M Meyer, MD VA San Diego and VMRF
  More Information

No publications provided

Responsible Party: Jonathan M. Meyer, MD, Research Scientist, Veterans Medical Research Foundation
ClinicalTrials.gov Identifier: NCT01411930     History of Changes
Other Study ID Numbers: 080225
Study First Received: September 15, 2009
Last Updated: December 19, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Veterans Medical Research Foundation:
Insulin resistance
Antipsychotics
Olanzapine
Aripiprazole

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Insulin
Aripiprazole
Olanzapine
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents

ClinicalTrials.gov processed this record on October 19, 2014