Insulin Resistance Intervention After Stroke Trial (IRIS)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Takeda Pharmaceuticals North America, Inc.
Information provided by (Responsible Party):
Yale University
ClinicalTrials.gov Identifier:
NCT00091949
First received: September 20, 2004
Last updated: June 23, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Stroke
Myocardial Infarction
Diabetes
Drug: pioglitazone
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Insulin Resistance Intervention After Stroke (IRIS) Trial

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • Time to occurrence of recurrent fatal or non-fatal stroke, or fatal or non-fatal myocardial infarction [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 1.time to stroke alone; 2.Diabetes Mellitus; 3.All Cause Mortality; 4.Cognitive Decline (change in score over time for the Modified Mini Mental State Examination) [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  • stroke, MI, or congestive heart failure [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 3936
Study Start Date: February 2005
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
pioglitazone
Drug: pioglitazone
a thiazolidinedione drug
Placebo Comparator: 2 Drug: placebo
an inactive substance

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 drugs (called "TZDs") 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 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.

  Eligibility

Ages Eligible for Study:   40 Years and older
Genders Eligible for Study:   Both
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. 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00091949

  Show 183 Study Locations
Sponsors and Collaborators
Yale University
Takeda Pharmaceuticals North America, Inc.
Investigators
Principal Investigator: Walter N. Kernan, M.D. Yale University
  More Information

No publications provided by Yale University

Additional 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
Study First Received: September 20, 2004
Last Updated: June 23, 2014
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on July 23, 2014