Diabetes Mellitus, Insulin Resistance
Conditions
Keywords
Insulin Resistance, Diabetes mellitus, Antipsychotic
Brief summary
The purpose of this clinical research study is to examine the acute hormonal and metabolic effects of the drug olanzapine, as well as appetite effects, in healthy volunteers. The hypotheses to be tested are that: (1) Olanzapine rapidly attenuates plasma leptin and (2) rapidly alters glucose tolerance in healthy volunteers. These questions will be answered by having volunteers undergo two glucose tolerance tests in a crossover study design.
Interventions
DRUGOlanzapine 10 mg po qhs for 3 days
(1) 10 mg tablets administered orally before bed for three consecutive evenings (Total Dose = 30 mg, 3 tablets)
DRUGPlacebo
(1) placebo tablets administered orally before bed for three consecutive evenings (Total Dose = 3 tablets)
Sponsors
American Medical Association
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Volunteer * Body Mass Index of 18.5-25 kilograms per square meter * Must be able to swallow tablets * Able to give informed consent
Exclusion criteria
* Any DSM-IV TR Axis I psychiatric disorder (except nicotine dependence) * Presence of any medical disorder that may confound the assessment of relevant biologic measures, including: significant organ system dysfunction, metabolic diseases, type 1 diabetes mellitus, type 2 diabetes mellitus, pregnancy, endocrine disease, coagulopathy, clinically significant anemia, or acute infection * Subjects who have taken any antipsychotic medication within the last 6 months * Personal or family history of seizures and/or cardiac arrhythmias
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Leptin | 3 Days | Leptin following placebo or olanzapine treatment |
| Oral Glucose Tolerance | 3 Days | Oral Glucose Tolerance |
| Plasma Free Fatty Acid | 3 Days | Plasma Free Fatty Acid |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total Cholesterol | 3 Days | Total Cholesterol |
| Body Weight | 3 Days | Body Weight |
| BMI | 3 Days | BMI |
| HDL Cholesterol | 3 Days | HDL Cholesterol |
| Systolic Blood Pressure | 3 Days | Systolic Blood Pressure |
| Diastolic Blood Pressure | 3 Days | Diastolic Blood Pressure |
| Heart Rate | 3 Days | Heart Rate |
| Triglycerides | 3 Days | Triglycerides |
| LDL Cholesterol | 3 Days | LDL Cholesterol |
Countries
United States
Participant flow
Recruitment details
A total of 42 individuals were screened between July 2008 and June 2009, and of those individuals 15 subjects were eligible based on inclusion/exclusion criteria.
Pre-assignment details
Only individuals that met inclusion/exclusion criteria were allowed to participate in the study. Of the 42 individuals screened, only 15 met criteria and were interested in taking part in the study. There was a minimum 2 week washout period in between treatment arms (i.e. placebo vs active compound).
Participants by arm
| Arm | Count |
|---|---|
| Placebo / Olanzapine Participants that were randomized to Placebo (Sugar Pill) treatment for three days and then a washout period of at least two weeks but not more than 4 weeks before Olanzapine treatment, 10 mg olanzapine by mouth at bedtime for three consecutive nights.
OR
Participants that were randomized to Olanzapine, 10 mg olanzapine by mouth at bedtime for three consecutive nights before a washout period of at least two weeks but not more than 4 weeks before Placebo treatment (Sugar Pill) for three days. | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Placebo / Olanzapine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 26.6 years STANDARD_DEVIATION 0.5 |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Oral Glucose Tolerance
Oral Glucose Tolerance
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Oral Glucose Tolerance | 2808 min*mg/dl | Standard Deviation 474 |
| Olanzapine | Oral Glucose Tolerance | 3984 min*mg/dl | Standard Deviation 444 |
p-value: 0.0105Wilcoxon Sign-rank
Primary
Plasma Free Fatty Acid
Plasma Free Fatty Acid
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Free Fatty Acid | 0.38 mM | Standard Deviation 0.06 |
| Olanzapine | Plasma Free Fatty Acid | 0.26 mM | Standard Deviation 0.04 |
p-value: 0.0166Wilcoxon Sign-rank
Primary
Plasma Leptin
Leptin following placebo or olanzapine treatment
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Plasma Leptin | 6.8 ng/ml | Standard Deviation 1.3 |
| Olanzapine | Plasma Leptin | 8.4 ng/ml | Standard Deviation 1.7 |
p-value: 0.0203Wilcoxon Signed-rank
Secondary
BMI
BMI
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | BMI | 23.0 kg / m2 | Standard Error 0.5 |
| Olanzapine | BMI | 23.0 kg / m2 | Standard Error 0.6 |
Secondary
Body Weight
Body Weight
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Body Weight | 68.2 kg | Standard Error 2.9 |
| Olanzapine | Body Weight | 68.9 kg | Standard Error 3 |
Secondary
Diastolic Blood Pressure
Diastolic Blood Pressure
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Diastolic Blood Pressure | 68.3 mmHg | Standard Error 2 |
| Olanzapine | Diastolic Blood Pressure | 69.5 mmHg | Standard Error 1.8 |
Secondary
HDL Cholesterol
HDL Cholesterol
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | HDL Cholesterol | 54.2 mg/dl | Standard Deviation 4.7 |
| Olanzapine | HDL Cholesterol | 48.9 mg/dl | Standard Deviation 4.3 |
p-value: 0.0184Wilcoxon Sign-rank
Secondary
Heart Rate
Heart Rate
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Heart Rate | 69.9 beats per minute | Standard Error 2.6 |
| Olanzapine | Heart Rate | 67.6 beats per minute | Standard Error 3.5 |
Secondary
LDL Cholesterol
LDL Cholesterol
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | LDL Cholesterol | 82.7 mg/dl | Standard Deviation 6.6 |
| Olanzapine | LDL Cholesterol | 81.7 mg/dl | Standard Deviation 7.8 |
Secondary
Systolic Blood Pressure
Systolic Blood Pressure
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Systolic Blood Pressure | 113.3 mmHg | Standard Error 2.8 |
| Olanzapine | Systolic Blood Pressure | 111.7 mmHg | Standard Error 3.1 |
Secondary
Total Cholesterol
Total Cholesterol
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Total Cholesterol | 156.8 mg/dl | Standard Deviation 9.1 |
| Olanzapine | Total Cholesterol | 152.6 mg/dl | Standard Deviation 10.1 |
Secondary
Triglycerides
Triglycerides
Time frame: 3 Days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Triglycerides | 88.9 mg/dl | Standard Deviation 10.1 |
| Olanzapine | Triglycerides | 108.2 mg/dl | Standard Deviation 11.6 |
p-value: 0.017Wilcoxon Sign-rank