Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia

NCT00231894 | Completed Phase 4 Results FDA Drug

• 2 other identifiers: 04T-584 Stanley Foundation04T-584
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes; Schizophrenia; Insulin Resistance; Cognitive Impairment

Keywords

atypical antipsychotics; hyperglycemia; triglycerides; HDL; cholesterol; insulin resistance; schizophrenia; verbal memory

Outcome Measures

Primary Outcomes (4)

• Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample

  pre-treatment and during 3 months of treatment

• Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample

  serum high density lipoprotein (HDL)

  pre-treatment and during 3 months of treatment

• Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample

  pretreatment and during 3 months of drug treatment

• 2 Hour Glucose From Glucose Tolerance Test US Sample

  difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment

  between baseline and 3 months of study drug treatment

Secondary Outcomes (5)

• Change in RBANS List Recognition Scores at 3 Months (3 Months-baseline) US Sample

  pre-treatment and 3 months of treatment

• Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample

  pretreatment and during 3 months of drug treatment

• Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample

  pretreatment and during 3 months of drug treatment

• 2 Hour Glucose From Glucose Tolerance Test China Sample

  between baseline and 3 months of study drug treatment

• Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site

  pretreatment and during 3 months of drug treatment

Study Arms (2)

Pioglitazone and life-style group

ACTIVE COMPARATOR

Pioglitazone (30-45 mg/daily) plus life-style diet group

Drug: Pioglitazone; Behavioral: Life style diet group

Placebo and life style group

PLACEBO COMPARATOR

Placebo capsules daily plus life-style diet group

Behavioral: Life style diet group; Other: Placebo

Interventions

Pioglitazone DRUG

pioglitazone 30-45 mg/day

Also known as: Actos

Pioglitazone and life-style group

Life style diet group BEHAVIORAL

life style diet education group 1x/week

Pioglitazone and life-style group; Placebo and life style group

Placebo OTHER

placebo comparator capsules

Placebo and life style group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patients will have evidence of:
• 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;
• Triglyceride levels \> 120 mg/dL and/or HDL levels \< 40 mg/dL

You may not qualify if:

• Diabetes mellitus, type 1
• Recent diabetic ketoacidosis;
• 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);
• 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;
• Congestive heart failure (Class III or IV cardiac status) or history of MI in medical record (because pioglitazone can increase blood volume slightly);
• Hematocrit greater than 10% below normal (hematocrit may be decreased 2 to 4% due to increased plasma volume);
• Female patients on current oral contraceptives (because pioglitazone may interfere with effects of some oral contraceptives);
• Patients taking ketoconazole,
• 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).
• Patients are not concomitantly treated with aripiprazole or ziprasidone.

Sponsors & Collaborators

• Nathan Kline Institute for Psychiatric Research: lead

Study Sites (1)

Nathan Kline Institute for Psychiatric Research

New York, New York, 10035, United States

Location

Related Publications (2)

• Smith RC et al Pioglitazone as a treatment for glucose and lipid abnormalities in schizophrenic patents: A double-blind placebo controlled trial. NCDEU 51lst Annual Meeting Oral Presentation Abstract Book, 2011, p.13.

  RESULT

• Smith RC, Jin H, Li C, Bark N, Shekhar A, Dwivedi S, Mortiere C, Lohr J, Hu Q, Davis JM. Effects of pioglitazone on metabolic abnormalities, psychopathology, and cognitive function in schizophrenic patients treated with antipsychotic medication: a randomized double-blind study. Schizophr Res. 2013 Jan;143(1):18-24. doi: 10.1016/j.schres.2012.10.023. Epub 2012 Nov 29.

  PMID: 23200554 RESULT

MeSH Terms

Conditions

Diabetes Mellitus; Schizophrenia; Insulin Resistance; Cognitive Dysfunction; Hyperglycemia

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Hyperinsulinism; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Sufficient RBANS data at baseline and 3 months followup for China sample was not available for analysis. Subjects failed to complete scales or complete scales with sufficient data.

Results Point of Contact

• Title: Robert C. Smith MD
• Organization: Nathan Kline Institute ofr Psychiatric research

rsmith@nki.rfmh.org

845-398-6531

Study Officials

• Robert C Smith, MD PhD

  NYU School of Medicine & Nathan Kline Institute for Psychiatric Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Psychiatrist

Study Record Dates

• First Submitted: October 3, 2005
• First Posted: October 4, 2005
• Study Start: May 1, 2005
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: December 11, 2017
• Results First Posted: December 11, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)