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Insulin Resistance Intervention After Stroke Trial (IRIS)

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ClinicalTrials.gov Identifier: NCT00091949
Recruitment Status : Completed
First Posted : September 22, 2004
Results First Posted : October 28, 2016
Last Update Posted : October 28, 2016
Sponsor:
Collaborators:
National Institute of Neurological Disorders and Stroke (NINDS)
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Yale University

Study Description
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Brief Summary:
The purpose of this study is to determine if pioglitazone is effective in preventing future strokes or heart attacks among non-diabetic persons who have had a recent ischemic stroke.

Condition or disease Intervention/treatment Phase
Stroke Myocardial Infarction Diabetes Drug: pioglitazone Drug: placebo Phase 3

Detailed Description:

Among patients throughout the world who experience a transient ischemic attack (TIA)or ischemic stroke, subsequent stroke and heart attack are major causes of death and disability. Within 4 years of the initial TIA or ischemic stroke, 16 percent of patients will have a recurrent stroke and 9 percent will have a heart attack. Prevention of further vascular events, therefore, is critically important to the health of patients with stroke.

The IRIS trial will test a new treatment strategy based on evidence linking insulin resistance to increased risk for stroke and other vascular diseases. Insulin resistance is a condition in which insulin, a normal human hormone, does not work effectively because the body is resistant to its effects. This condition can lead to diabetes and is thought to cause blood vessel disease, including stroke and heart attack, in patients with and without diabetes.

Insulin resistance affects up to 50% of stroke patients and is effectively modified with thiazolidinedione (TZD) drugs used to treat type 2 diabetes. In addition to reducing insulin resistance, these drugs have other favorable effects on blood vessels, reduce blood vessel inflammation, and potentially prevent atherosclerosis. Currently marketed TZDs include rosiglitazone and pioglitazone.

The IRIS is a clinical trial that will enroll 3936 subjects at approximately 170 hospitals in Australia, Canada, Germany, Israel, Italy, the United Kingdom (UK) and the US. After an initial screening blood test, each participant will be randomly assigned to take either pioglitazone or placebo tablets. Recruitment will be completed during 2005-2012, and all participants will be followed for a minimum of 3 years.


Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3876 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Insulin Resistance Intervention After Stroke (IRIS) Trial
Study Start Date : February 2005
Actual Primary Completion Date : November 2015
Actual Study Completion Date : November 2015

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack
U.S. FDA Resources

Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Pioglitazone
pioglitazone
 Drug: pioglitazone
a thiazolidinedione drug
Placebo Comparator: Placebo
inactive substance
 Drug: placebo
an inactive substance


Outcome Measures
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Primary Outcome Measures :
  1. Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction [ Time Frame: Up to 5 years ]

Secondary Outcome Measures :
  1. Fatal or Non-fatal Stroke Alone [ Time Frame: 5 years ]
  2. Acute Coronary Syndrome [ Time Frame: 5 years ]
    Fatal or non-fatal acute myocardial infarction or unstable angina

  3. Development of Overt Diabetes [ Time Frame: 5 years ]
  4. All Cause Mortality [ Time Frame: 5 years ]
  5. Decline in Cognitive Status [ Time Frame: Annual measures from baseline to exit (up to 5 years) ]
    Change in modified mental status examination (3MS) score from baseline to exit. Theoretical range of 3MS scores is 0-100. Baseline scores ranged from 22-100.

  6. Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure [ Time Frame: 5 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

  1. Ages 40 years or greater at the time of randomization.
  2. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization
  3. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity (HOMA).
  4. Both ability and willingness to provide informed consent.
  5. Presence of none of the exclusion criteria.

Exclusion Criteria

Permanent Exclusions

  1. Severely disabling stroke as indicated by an inability to participate in scheduled follow-up activities.
  2. Persons whose ischemic stroke or TIA was related to structural cardiac lesion, significant head trauma, proximal arterial dissection or medical instrumentation.
  3. Diabetes mellitus as defined by recent use of medication for diabetes as an out-patient (*see note below) or two fasting plasma blood sugars > 126 mg/dL.
  4. HgbA1c > 7.0%.

  5. Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol. These include:

    • Cancer or other chronic disease with poor prognosis (predicted survival of less than four years).
    • Severe neurologic or psychiatric disease that would complicate the evaluation of study outcomes (e.g., dementia or schizophrenia).
  6. History of intolerance to any thiazolidinedione.
  7. Pregnancy or desire to become pregnant.
  8. Oral contraceptive use.
  9. Ongoing use of oral corticosteroids.
  10. History of heart failure
  11. Active liver disease as defined by known liver disease accompanied by cirrhosis, significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic synthetic dysfunction, or expected significant loss of liver function over the course of the study.
  12. History of bladder cancer.

  13. Current participation in a conflicting clinical trial. A conflicting clinical trial is defined as a trial with any of following:

    • Intervention that is known to affect the incidence of stroke or myocardial infarction.
    • Intervention that is an experimental drug.
    • Outcome that includes stroke or myocardial infarction.
    • Exclusion for participation in another trial.

Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the exclusion has resolved.

  1. Alanine aminotransferase (ALT) >2.5 times the upper limit of normal.
  2. Hemoglobin <8.5 g/dl.
  3. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4).
  4. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2 weeks following procedure).
Contacts and Locations
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00091949


  Show 183 Study Locations
Sponsors and Collaborators
Yale University
National Institute of Neurological Disorders and Stroke (NINDS)
Takeda Pharmaceuticals North America, Inc.
Investigators
Principal Investigator: Walter N. Kernan, M.D. Yale University
More Information
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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT00091949     History of Changes
Other Study ID Numbers: R01NS044876
U01NS044876 ( U.S. NIH Grant/Contract )
First Posted: September 22, 2004    Key Record Dates
Results First Posted: October 28, 2016
Last Update Posted: October 28, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

Keywords provided by Yale University:
stroke
heart attack
diabetes
pioglitazone
insulin resistance

Additional relevant MeSH terms:
Stroke
Infarction
Myocardial Infarction
Insulin Resistance
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Ischemia
 Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs