Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia
Condition: Diabetes; Schizophrenia; Insulin Resistance; Cognitive Impairment
MeSH terms: Insulin Resistance; Schizophrenia
Intervention: Pioglitazone; Life style diet group; Placebo
Intervention description: pioglitazone 30-45 mg/day; life style diet education group 1x/week; placebo comparator capsules
Intervention MeSH terms: Pioglitazone
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 56.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: atypical antipsychotics; hyperglycemia; triglycerides; HDL; cholesterol; insulin resistance; schizophrenia; verbal memory

Summary:

      This is a study with an approved drug for treating type 2 diabetes, for its effects on
      treating glucose and lipid abnormalities in patients being treated with first or
      second-generation antipsychotics, and comparison of effects of this drug with another
      treatment lifestyle modification. Patients who meet inclusion criteria will be treated with
      pioglitazone for 12 weeks. They will be evaluated for fasting glucose and lipids,
      glucose-tolerance tests, and neurocognitive battery and tests of verbal memory at baseline
      and during treatment with pioglitazone.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients will be males or females, 18-70 yrs of age, with a diagnosis of schizophrenia
             or schizoaffective disorder, and currently being treated with olanzapine or clozapine.

          2. Patients will have evidence of:

               1. glucose levels indicating at least impaired fasting glucose: fasting glucose 100
                  mg/dL or 2 hr glucose tolerance test 140 mg/dL, or current treatment with oral
                  antidiabetic drugs with history of hyperglycemia;

               2. Triglyceride levels > 120 mg/dL and/or HDL levels < 40 mg/dL

        Exclusion Criteria:

          1. Diabetes mellitus, type 1

          2. Recent diabetic ketoacidosis;

          3. Patients not currently treated with oral antidiabetic drugs but fasting is glucose 140
             mg/dL [WHO criteria] on repeat testing in last three months, or random blood glucose
             >200 mg/dL plus 2 hr glucose on GTT >200 mg/dL; (these patients may need more
             immediate treatment with antidiabetic drugs and it is less certain if weight-lifestyle
             treatment would be effective in treating such high glucose levels);

          4. Patients with active liver disease with clinical abnormalities which need current
             treatment, or liver enzymes (Alt) 3 times upper limit for normal values in chart
             records in last year, or patients who are recorded as positive for hepatitis C;

          5. Congestive heart failure (Class III or IV cardiac status) or history of MI in medical
             record (because pioglitazone can increase blood volume slightly);

          6. Hematocrit greater than 10% below normal (hematocrit may be decreased 2 to 4% due to
             increased plasma volume);

          7. Female patients on current oral contraceptives (because pioglitazone may interfere
             with effects of some oral contraceptives);

          8. Patients taking ketoconazole,

          9. Patients who have started on atorvastatin or gemfibrozil in the past 2 months or have
             had a dose increase in atorvastatin in the last month (since these drugs can also
             lower triglycerides and raise HDL, recent start of therapy with these drugs could be a
             confound).

         10. Patients are not concomitantly treated with aripiprazole or ziprasidone.