Ziprasidone for Improving Insulin Sensitivity in People With Schizophrenia Who Are at Risk for Diabetes

• Sponsor: Veterans Medical Research Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT00338949
• Collaborator: National Institute of Mental Health (NIMH) (NIH), Pfizer (Industry)
• Enrollment: 77
• Location: 1
• Arms: 2
• Duration (Months): 42
• Patients Per Site Per Month: 1.8

Study Details

Study Description

Brief Summary

This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Metabolic Syndrome X; Insulin Resistance	Drug: Switch; Drug: Control	Phase 4

Detailed Description

People with schizophrenia often lead more sedentary lifestyles than people without the disease, and they are frequently treated with antipsychotic medications that cause weight gain. Combined, these factors produce an increased risk for metabolic syndrome, which can lead to heart disease and type 2 diabetes. Characteristics of metabolic syndrome include carrying excess weight around the abdominal region; high blood pressure; high blood sugar levels; high levels of fat in the blood; and low levels of HDL cholesterol. Recent studies have shown that certain atypical antipsychotic drugs are relatively weight-neutral. Switching from a drug that promotes weight gain to a weight-neutral medication, such as ziprasidone, may result in significant weight loss. There is insufficient evidence, however, demonstrating the extent of improvement in insulin sensitivity after switching medications. This study will evaluate the effectiveness of ziprasidone treatment versus treatment with a standard atypical antipsychotic drug in improving insulin sensitivity and reducing excess abdominal fat storage in people with schizophrenia who are at risk for diabetes.

Participants in this open label study will currently be undergoing treatment with risperidone or olanzapine at the time of study entry. Upon study entry, they will be randomly assigned to either switch to ziprasidone treatment or remain on their current medications. Both groups will be treated for 26 weeks. Participants will report to the study site for evaluations biweekly until week 10 and then monthly for the duration of the study. The primary outcomes at Week 26 will be: change from baseline in insulin sensitivity, using an intravenous glucose tolerance test; change from baseline in ivisceral fat mass, using a CT scan.

Study Design

• Study Type: Interventional
• Actual Enrollment: 77 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Metabolic Syndrome in Patients With Schizophrenia
• Study Start Date: Jun 1, 2006
• Actual Primary Completion Date: Dec 1, 2009
• Actual Study Completion Date: Dec 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Participants on risperidone or olanzapine who will remain on risperidone or olanzapine and do not switch to ziprasidone	Drug: Control; Participants will remain taking the same medications of risperidone or olanzapine as they were before study entry.; Other Names: risperidone olanzapine
Experimental: Switch Participants who enter on risperidone or olanzapine and switch to ziprasidone	Drug: Switch; Participants who are switched to ziprasidone will take a max daily dose of 200 mg, flexibly dosed based on symptoms and adverse effects.; Other Names: ziprasidone

Outcome Measures

Primary Outcome Measures

1. Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min) [Measured at Baseline and Week 26]

   As measured by frequently sampled intravenous glucose tolerance testing (units: 1/mU/L) x 1/Min)

2. Change in Visceral Fat Mass From Baseline to Week 26 [Baseline and Week 26]

   CT measured change in visceral fat mass from baseline to week 26 (mm^3)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of schizophrenia or schizoaffective disorder

• Currently receiving antipsychotic therapy with risperidone or olanzapine

• Overweight

Exclusion Criteria:

• Diagnosis of diabetes

• Hospitalization for schizophrenia or schizoaffective disorder within 90 days prior to study entry

• Refractory schizophrenia or schizoaffective disorder

• Currently receiving therapy with clozapine

• No stable residence and phone number for 90 days prior to study entry

• Prior unsuccessful treatment with ziprasidone

• Intolerance to ziprasidone

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	VA San Diego Healthcare System	San Diego	California	United States	92161

Sponsors and Collaborators

• Veterans Medical Research Foundation
• National Institute of Mental Health (NIMH)
• Pfizer

Investigators

• Principal Investigator: Jonathan M. Meyer, MD, University of California, San Diego & VA San Diego Healthcare System

Study Documents (Full-Text)

None provided.

More Information

Publications

• McEvoy JP, Meyer JM, Goff DC, Nasrallah HA, Davis SM, Sullivan L, Meltzer HY, Hsiao J, Scott Stroup T, Lieberman JA. Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III. Schizophr Res. 2005 Dec 1;80(1):19-32. Epub 2005 Aug 30.

• Responsible Party: Jonathan M. Meyer, MD, Research Scientist, Veterans Medical Research Foundation
• ClinicalTrials.gov Identifier: NCT00338949
• Other Study ID Numbers: K23MH074540; K23MH074540; GA128029
• First Posted: Jun 20, 2006
• Last Update Posted: Oct 30, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Jonathan M. Meyer, MD, Research Scientist, Veterans Medical Research Foundation: Ziprasidone; Olanzapine; Risperidone; Schizoaffective Disorder; Insulin Sensitivity; Visceral Adiposity; Metabolic Syndrome
• Additional relevant MeSH terms: Metabolic Syndrome; Insulin Resistance; Syndrome; Schizophrenia; Olanzapine; Risperidone; Ziprasidone

Study Results

Participant Flow

Recruitment Details	Recruitment started 06/01/2006. Eligibility: nondiabetic, overweight/obese psychiatrically stable adult outpatients in San Diego with schizophrenia/schizoaffective disorder, on risperidone or olanzapine. Recruitment ended: 12/31/2009
Pre-assignment Detail	Exclusions: unstable housing, psychiatric hospitalization in the past 90 days, ongoing substance abuse (except nicotine), history of diabetes mellitus, pregnancy, refractory schizophrenia, prior failure of or intolerance to ziprasidone, oral glucose tolerance test indicative of diabetes mellitus, or corrected QT interval ≥ 500 msec on EKG.

Arm/Group Title	Control	Switch
Arm/Group Description	Remain on risperidone or olanzapine.	Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food).
Period Title: Subject Screening
STARTED	36	41
COMPLETED	25	30
NOT COMPLETED	11	11
Period Title: Subject Screening
STARTED	25	30
COMPLETED	24	25
NOT COMPLETED	1	5

Baseline Characteristics

Arm/Group Title	Control	Switch	Total
Arm/Group Description	Remain on risperidone or olanzapine.	Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food).	Total of all reporting groups
Overall Participants	25	30	55
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.15 (8.15)	48.73 (8.42)	48.00 (8.30)
Sex: Female, Male (Count of Participants)
Female	6 24%	7 23.3%	13 23.6%
Male	19 76%	23 76.7%	42 76.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 8%	4 13.3%	6 10.9%
Not Hispanic or Latino	23 92%	26 86.7%	49 89.1%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 28%	10 33.3%	17 30.9%
White	18 72%	20 66.7%	38 69.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%	30 100%	55 100%
Family Diabetes Mellitus History (participants) [Number]
Family Hx	4 16%	5 16.7%	9 16.4%
No Family Hx	21 84%	25 83.3%	46 83.6%
Smoking Status (participants) [Number]
Smoker	16 64%	18 60%	34 61.8%
Nonsmoker	9 36%	12 40%	21 38.2%
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	32.52 (4.49)	34.64 (7.60)	33.68 (6.19)
Baseline Antipsychotic (participants) [Number]
Risperidone	17 68%	21 70%	38 69.1%
Olanzapine	8 32%	9 30%	17 30.9%
PANSS Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	62.72 (11.70)	65.20 (10.66)	64.07 (11.13)
Central visceral fat volume by CT (mm^3) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm^3]	28442 (10634)	26939 (12060)	27622 (11412)
Insulin sensitivity index ((1/mU/L) x 1/Min) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [(1/mU/L) x 1/Min]	1.596 (1.00)	1.504 (0.902)	1.55 (0.95)

Outcome Measures

1. Primary Outcome

Title	Change in Insulin Sensitivity Index From Baseline to Week 26 ((1/mU/L) x 1/Min)
Description	As measured by frequently sampled intravenous glucose tolerance testing (units: 1/mU/L) x 1/Min)
Time Frame	Measured at Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Control	Switch
Arm/Group Description	Remain on risperidone or olanzapine.	Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food).
Measure Participants	24	25
Mean (Standard Deviation) [(1/mU/L) x 1/Min]	0.072 (0.955)	0.407 (0.822)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Switch
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.228
	Comments
	Method	t-test, 2 sided
	Comments

2. Primary Outcome

Title	Change in Visceral Fat Mass From Baseline to Week 26
Description	CT measured change in visceral fat mass from baseline to week 26 (mm^3)
Time Frame	Baseline and Week 26

Outcome Measure Data

Analysis Population Description

Completers

Arm/Group Title	Control	Switch
Arm/Group Description	Remain on risperidone or olanzapine.	Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food).
Measure Participants	24	25
Mean (Standard Deviation) [mm^3]	315 (5693)	392 (4340)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Switch
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.958
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	6 months
Arm/Group Title	Control		Switch
Arm/Group Description	Remain on risperidone or olanzapine.		Switch from risperidone or olanzapine to ziprasidone. Ziprasidone will be flexibly dosed based on tolerability and psychiatric response (max dose 200 PO mg/d with food).
All Cause Mortality
	Control		Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Control		Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/25 (4%)		2/30 (6.7%)
Psychiatric disorders
Psychiatric exacerbation	1/25 (4%)	1	2/30 (6.7%)	2
Other (Not Including Serious) Adverse Events
	Control		Switch
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		3/30 (10%)
Psychiatric disorders
Insomnia	0/25 (0%)	0	2/30 (6.7%)	2
Akathisia	0/25 (0%)	0	1/30 (3.3%)	1

Limitations/Caveats

Open label, stable patients.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.