DiabetesPhase 4NCT00231894

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

A Phase 4 study testing Pioglitazone and Life style diet group in people with Diabetes and Schizophrenia, run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Diabetes, Schizophrenia, Insulin Resistance
What is being tested?: Pioglitazone and Life style diet group
Type of treatment: Pill or oral medicine, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 56 participants
Where: 1 siteUnited States
Study dates: May 2005to Jan 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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);

Show all 10Show fewer

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Nathan Kline Institute for Psychiatric Research
New York, New York, 10035

Other trials in United States

About this study

Official title: Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia Treated With Antipsychotic Medication And Potential Effects on Cognitive Function

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.

Read the detailed description

The aim of this study is to investigate the effects of pioglitazone added to weight-lifestyle intervention vs. placebo plus lifestyle intervention on reversing or reducing impaired or abnormal triglycerides, HDL and glucose metabolism in schizophrenics treated with first or second-generation antipsychotics.. Another aim is to examine the effects of impaired glucose metabolism on verbal memory and other cognitive function in schizophrenic patients treated with these medications and the relationship to improvements in impaired glucose metabolism to impairments in cognitive function. Clozapine and olanzapine, and some other first or second-generation antipsychotics effective for treating schizophrenia and bipolar disorders, have been reported to be associated with increased incidence of diabetic type metabolic abnormalities, decreases in insulin sensitivity, and abnormal glucose tolerance tests. This can lead to the development of type 2 diabetes and also abnormal lipid metabolic levels which can lead to atherosclerotic changes and increased risk of cardiovascular disease and other diabetes related complications. Drug treatments which could reduce or correct these diabetic metabolic changes would permit many patients to continue to receive the benefits of these antipsychotic medications with reduced drug-induced comorbidity. Previous research using non-psychotic subjects has shown that diabetes and impaired glucose tolerance are associated with cognitive impairments, especially in verbal memory, and provides a rationale for testing whether corrections of impaired glucose metabolism are associated with cognitive improvements in schizophrenic patients.

Conditions: Diabetes, Schizophrenia, Insulin Resistance, Cognitive Impairment
Being tested: Pioglitazone, Life style diet group, Placebo
Keywords: atypical antipsychotics, hyperglycemia, triglycerides, HDL, cholesterol, insulin resistance, schizophrenia, verbal memory
Medical subject headings: Diabetes Mellitus, Schizophrenia, Insulin Resistance, Cognitive Dysfunction, Hyperglycemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

PioglitazoneDrug
Also called Actos
pioglitazone 30-45 mg/day
Life style diet groupBehavioural
life style diet education group 1x/week
PlaceboOther
placebo comparator capsules

Study groups in NCT00231894
Study group	Role	What they receive
Pioglitazone and life-style group	Active comparator	Pioglitazone (30-45 mg/daily) plus life-style diet group Receives: Drug: Pioglitazone; Behavioral: Life style diet group
Placebo and life style group	Placebo comparator	Placebo capsules daily plus life-style diet group Receives: Behavioral: Life style diet group; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
Measured: 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)
Measured: pre-treatment and during 3 months of treatment
Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample
Measured: 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
Measured: 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
The scale is Repeatable Battery for the Assessment to Neuropsychological Status (RBANS). This scale measure cognitive function in patients with schizophrenia. Range for list learning sub-score is 0 to 20 . Higher values indicate better performance. For change score (3 months -baseline) positive values indicate improved performance for this cognitive function and negative values indicate poorer performance on this cognitive function.
Measured: pre-treatment and 3 months of treatment
Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample
Measured: pretreatment and during 3 months of drug treatment
Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample
Measured: pretreatment and during 3 months of drug treatment
2 Hour Glucose From Glucose Tolerance Test China Sample
difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment
Measured: between baseline and 3 months of study drug treatment
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site
Measured: pretreatment and during 3 months of drug treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

May 2005Jan 2010

First posted4 Oct 2005 (estimated)
Study startMay 2005
Primary completionJan 2010
Study completionJan 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 56 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00231894
Sponsor's protocol ID: 04T-584 Stanley Foundation
Other IDs: 04T-584
Status last verified: Nov 2017
First submitted: 3 Oct 2005
Last updated: 11 Dec 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

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.
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.
PubMed 23200554

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

All Diabetes trials

Study at a glance

From the registry record, last updated by the sponsor on 11 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pioglitazone as a Treatment for Lipid and Glucose Abnormalities In Patients With Schizophrenia Treated With Antipsychotic Medication And Potential Effects on Cognitive Function
ClinicalTrials.gov ID: NCT00231894
Acronym / sponsor ID: 04T-584 Stanley Foundation
Conditions: Diabetes, Schizophrenia, Insulin Resistance, Cognitive Impairment
Keywords: atypical antipsychotics, hyperglycemia, triglycerides, HDL, cholesterol, insulin resistance, schizophrenia, verbal memory
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 56 participants (actual)
Lead sponsor: Nathan Kline Institute for Psychiatric ResearchUniversity, hospital or other
Study start: May 2005
Primary completion: Jan 2010 (actual)
Study completion: Jan 2010 (actual)
First posted: 4 Oct 2005 (estimated)
Results: Posted 11 Dec 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Pioglitazone and life-style group	Active comparator	Drug: Pioglitazone, Behavioral: Life style diet groupPioglitazone (30-45 mg/daily) plus life-style diet group
Placebo and life style group	Placebo comparator	Behavioral: Life style diet group, Other: PlaceboPlacebo capsules daily plus life-style diet group

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

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:

Key exclusion criteria (10 listed)

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);

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
PioglitazoneAlso: Actospioglitazone 30-45 mg/day	Drug	Pioglitazone and life-style group
Life style diet grouplife style diet education group 1x/week	Behavioural	Pioglitazone and life-style group, Placebo and life style group
Placeboplacebo comparator capsules	Other	Placebo and life style group

Primary outcome

Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample
Time frame: pre-treatment and during 3 months of treatment
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample
Time frame: pre-treatment and during 3 months of treatment
serum high density lipoprotein (HDL)
Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample
Time frame: pretreatment and during 3 months of drug treatment
2 Hour Glucose From Glucose Tolerance Test US Sample
Time frame: between baseline and 3 months of study drug treatment
difference between 2 hr glucose for GTT test at baseline vs after 3 months of drug treatment

5 secondary outcomes

Change in RBANS List Recognition Scores at 3 Months (3 Months-baseline) US Sample
Time frame: pre-treatment and 3 months of treatment
Change From Baseline in Serum Glucose at 3 Months ( 3 Months -Baseline) China Sample
Time frame: pretreatment and during 3 months of drug treatment
Change From Baseline in Serum Triglycerides at 3 Months (3 Months-baseline) China Sample
Time frame: pretreatment and during 3 months of drug treatment
2 Hour Glucose From Glucose Tolerance Test China Sample
Time frame: between baseline and 3 months of study drug treatment
Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) China Site
Time frame: pretreatment and during 3 months of drug treatment

Results and safety

Results posted to the registry on 11 Dec 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pioglitazone	31	30
Placebo	25	24

Primary outcome: Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample

Time frame: pre-treatment and during 3 months of treatment. Least squares mean (Standard Error). Unit: mg/dL

Measure	Pioglitazone n = 25	Placebo n = 19
Value	-49.65 (24.01)	30.99 (26.82)

Population analysed: Data is from participants at U.S. sites N=44, Pioglitazone =25, Placebo =19, who had values of triglycerides at baseline and three months followup. See table 2 of published paper given in reference for further details.

Primary outcome: Change From Baseline in Serum HDL at 3 Months (3 Months-baseline) US Sample

Time frame: pre-treatment and during 3 months of treatment. Least squares mean (Standard Error). Unit: mg/dL

Measure	Piogltiazone n = 25	Placebo n = 19
Value	4.62 (1.77)	-2.59 (2.11)

Population analysed: Data is from participants at U.S. sites N=44, Pioglitazone =25, Placebo =19, who had values of HDL at baseline and three months followup. See table 2 of published paper and its supplementary data paper cited in reference for further details.

Primary outcome: Change From Baseline in Serum Glucose at 3 Months (3 Months-baseline) US Sample

Time frame: pretreatment and during 3 months of drug treatment. Least squares mean (Standard Error). Unit: mg/dL

Measure	Pioglitazone n = 25	Placebo n = 19
Value	0.02 (8.14)	24.20 (8.63)

Population analysed: Data is from participants at U.S. sites N=44, Pioglitazone =25, Placebo =19, who had values of serum glucose at baseline and three months follow-up. See table 2 of published paper and its supplementary data paper cited in reference for further details.

Primary outcome: 2 Hour Glucose From Glucose Tolerance Test US Sample

Time frame: between baseline and 3 months of study drug treatment. Least squares mean (Standard Error). Unit: mg/dL

Measure	Pioglitazone n = 25	Placebo n = 19
Value	-24.19 (17.03)	15.19 (17.75)

Population analysed: Data is from participants at U.S. sites N=44, Pioglitazone =25, Placebo =19, who had values of serum glucose at 2-hour point in glucose tolerance test at baseline and three months follow-up. See table 2 of published paper and its supplementary data paper cited in reference for further details.

5 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 3% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pioglitazone	0 of 31 (0%)	1 of 31 (3.2%)	Not reported
Placebo	0 of 25 (0%)	2 of 25 (8%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publicationSmith 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.
Results publication: PubMed 23200554Smith 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.
Individual participant dataSharing planned: No

Related trials for Diabetes

Not yet recruitingPhase 3
Efficacy and Safety of Once-Weekly SHR-3167 Compared With Once-Daily Insulin Glargine in Adults With Insulin-Naive Type 2 Diabetes
Type 2 Diabetes
Active, not recruiting
Digital Reinforcement of Motivational Interviewing Micro-Skills Among Primary Care Healthcare Professionals
Hypertension (Without Type 2 Diabetes Mellitus)
Recruiting
Effects of Lean Pork Loin Intake on Protein Homeostasis and Glucose Regulation in Prediabetic Adults
Hyperglycaemia (Non Diabetic), Prediabetes
Recruiting
PAW-Hydrogel for Chronic Wound Healing
Diabetic Foot Ulcer (DFU), Pressure Ulcer (PU)
Recruiting
Investigating Vascular Properties of HEMI and SPG Signals in Individuals With or at Risk for Chronic Kidney Disease
Chronic Kidney Disease, Hypertension (HTN)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Robert C Smith, MD PhD principal investigator

NYU School of Medicine & Nathan Kline Institute for Psychiatric Research

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Pioglitazone and Life style diet group in people with Diabetes and Schizophrenia, run by Nathan Kline Institute for Psychiatric Research at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change From Baseline in Serum Triglycerides at 3 Months ( 3 Months-baseline) US Sample (time frame: pre-treatment and during 3 months of treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00231894, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2017.