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

  Hide Study Locations
Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294-0007
University of South Alabama
Mobile, Alabama, United States, 36617-2293
United States, Arizona
University of Arizona
Tucson, Arizona, United States, 85721-5023
United States, California
Shanti Clinical Trials (NINDS-CRC site)
Colton, California, United States, 92324
UCSF-Fresno
Fresno, California, United States, 93702
Scripps Clinic
La Jolla, California, United States, 92037
University of California
Los Angeles, California, United States, 90095
University of Southern California
Los Angeles, California, United States, 90033
Stanford University
Palo Alto, California, United States, 94304
University of California-Davis
Sacramento, California, United States, 95817
University of California
San Diego, California, United States, 92103-8466
University of California
San Francisco, California, United States, 94143-0114
United States, Colorado
Denver Health and Hospital Authority
Denver, Colorado, United States, 80204-4507
United States, Connecticut
Hartford
Hartford, Connecticut, United States, 06102-5037
Yale University
New Haven, Connecticut, United States, 06519
United States, District of Columbia
National Rehabilitation Hospital
Washington, District of Columbia, United States, 20010-2949
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
University of Florida
Jacksonville, Florida, United States, 32209
MIMA Century Research Associates
Melbourne, Florida, United States, 32901
Pines Neurological Associates (NINDS-CRC site)
Pembroke Pines, Florida, United States, 33026
Floria Neurovascular Institute
Tampa, Florida, United States, 33606-3500
United States, Illinois
Cook County (Stroger) Hospital
Chicago, Illinois, United States, 60612
University of Illinois
Chicago, Illinois, United States, 60612
Rush University
Chicago, Illinois, United States, 60612
Ingalls Memorial Hospital (NINDS-CRC site)
Harvey, Illinois, United States, 60426
Loyola University Medical Center
Maywood, Illinois, United States, 60153
OSF St. Francis Medical Center
Peoria, Illinois, United States, 61637-0001
Tri-City Neruology (NINDS-CRC site)
St. Charles, Illinois, United States, 60175
United States, Indiana
Indiana Medical Research
ELkhart, Indiana, United States, 46514
Associates In Neurology (NINDS-CRC site)
Valparaiso, Indiana, United States, 46383
United States, Iowa
Ruan Neuroscience Center/Mercy Medical Center
Des Moines, Iowa, United States, 50314
Iowa Health Des Moines Clinical Trials Office
Des Moines, Iowa, United States, 50309
University of Iowa
Iowa City, Iowa, United States, 52246
Northeast Iowa Medical Education Foundation (NINDS-CRC site)
Waterloo, Iowa, United States, 50702
United States, Kansas
Via Christi Regional Medical Center
Wichita, Kansas, United States, 67214
United States, Kentucky
University of Kentucky Research Foundation
Lexington, Kentucky, United States, 40536-0284
United States, Louisiana
Louisiana State University Health Sciences Center
Shreveport, Louisiana, United States, 71130-3932
United States, Maine
Penobscot Bay Neurology
Rockport, Maine, United States, 04856
United States, Maryland
Johns Hopkins
Baltimore, Maryland, United States, 21287-6953
Sinai Hospital of Baltimore
Baltimore, Maryland, United States, 21209
United States, Massachusetts
Boston University
Boston, Massachusetts, United States, 02118
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114-2695
Beth Israel Deaconess
Boston, Massachusetts, United States, 02215
Caritas St. Elizabeth's Medical Center
Boston, Massachusetts, United States, 02190
United States, Michigan
Henry Ford Hospital
Detroit, Michigan, United States, 48202
Michigan State University
East Lansing, Michigan, United States, 48824
United States, Minnesota
Minneapolis Clinic of Neurology
Robbinsdale, Minnesota, United States, 55426
United States, Mississippi
Hattiesburg Clinic (NINDS-CRC site)
Hattiesburg, Mississippi, United States, 39401
United States, Missouri
St. Luke's Brain and Stroke Institute
Kansas City, Missouri, United States, 64111
Washington University
St. Louis, Missouri, United States, 63110
St. Louis University
St. Louis, Missouri, United States, 63220
St. John's Mercy Medical Center
St. Louis, Missouri, United States, 63141
United States, Montana
Billings Clinic
Billings, Montana, United States, 59101
Advanced Neurology Specialists
Great Falls, Montana, United States, 59405
United States, Nebraska
University of Nebraska
Omaha, Nebraska, United States, 68198
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08013
Kessler Medical Rehab Research Corp
West Orange, New Jersey, United States, 07052
United States, New Mexico
University of New Mexico
Albuquerque, New Mexico, United States, 87108
United States, New York
Albany Medical Center
Albany, New York, United States, 12208
New York Methodist Hospital
Brooklyn, New York, United States, 11215
SUNY Downstate
Brooklyn, New York, United States, 11203
SUNY Buffalo
Buffalo, New York, United States, 14209
Cornell University
New York, New York, United States, 10021
St. Vincent's Hospital Manhattan
New York, New York, United States, 10011
University of Rochester
Rochester, New York, United States, 14642
Southtowns Neurology of WNY (NINDS-CRC site)
West Seneca, New York, United States, 14224
Burke Medical Research Institute
White Plains, New York, United States, 10605
United States, North Carolina
Clinical Research of Winston-Salem
Winston-Salem, North Carolina, United States, 27103
Guilford Neurologic Associates
Winston-Salem, North Carolina, United States, 27103
United States, North Dakota
Altru Health System
Grand Forks, North Dakota, United States, 58201
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267-0525
Case Western Reserve University
Cleveland, Ohio, United States, 44106-4938
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
Metrohealth Medical Center
Cleveland, Ohio, United States, 44109-1998
Ohio State University
Columbus, Ohio, United States, 43210
University of Toledo
Toledo, Ohio, United States, 43614
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States, 97239-3098
United States, Pennsylvania
Abington Memorial Hospital
Abington, Pennsylvania, United States, 19001
Lankenau Institute for Medical Research
Bryn Mawr, Pennsylvania, United States, 19010
Penn Stat-Hershey Medical Center (NINDS-CRC site)
Hershey, Pennsylvania, United States, 17033
Temple University
Philadelphia, Pennsylvania, United States, 19140
Thomas Jefferson University
Philadelphia, Pennsylvania, United States, 19107-5083
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213-2582
Allegheny Singer Research Institute
Pittsburgh, Pennsylvania, United States, 15212
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02905
United States, Tennessee
University of Tennessee
Memphis, Tennessee, United States, 38163
Vanderbilt
Nashville, Tennessee, United States, 37212
United States, Texas
University of Texas, Southwestern
Dallas, Texas, United States, 75390-8897
Baylor Research Institute
Dallas, Texas, United States, 75246
Methodist Neurological Institute
Houston, Texas, United States, 77030
University of Texas
San Antonio, Texas, United States, 78229-3900
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
United States, Vermont
University of Vermont
Burlington, Vermont, United States, 05405
United States, Virginia
University of Virginia
Charlottesville, Virginia, United States, 22908
Sentara Medical Group
Norfolk, Virginia, United States, 23507
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53792
Marshfield Clinic
Marshfield, Wisconsin, United States, 54449
Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226-3596
Australia, New South Wales
Flinders Medical Centre
Bedford Park, New South Wales, Australia, 5042
Royal Prince Alfred
Camperstown, New South Wales, Australia, 2050
John Hunter Hospital (University of Newcastle)
New Lambton Heights, New South Wales, Australia, 2305
Australia, Victoria
Box Hill Hospital (Eastern Health)
Box Hill, Victoria, Australia, 3128
Western Hospital (University of Melbourne)
Footscray, Victoria, Australia, 3011
Austin Health (National Stroke Research Institute)
Heidelberg Heights, Victoria, Australia, 3801
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Australia, Western Australia
Royal Perth
Perth, Western Australia, Australia, 6000
Canada, Alberta
University of Alberta
Edmonton, Alberta, Canada, T6G2B7
Center for Neurologic Research
Lethbridge, Alberta, Canada, T1J0N9
Canada, British Columbia
Vancouver Island Health Research Centre
Victoria, British Columbia, Canada, V8R4R2
Canada, Ontario
Robarts Research Institute
London, Ontario, Canada, N6G2V2
Ottawa Hospital-General Campus
Ottawa, Ontario, Canada, k1Y 4E9
Intermountain Research Consultants
Thunder Bay, Ontario, Canada, P7B7C7
St. Michael's Hospital
Toronto, Ontario, Canada, M5B1W8
Canada, Quebec
Hôpital Charles LeMoyne
Greenfield Park, Quebec, Canada, J4V 2H1
McGill-Jewish General
Montreal, Quebec, Canada, H3T1E2
McGill-Montreal General
Montreal, Quebec, Canada, H3G1A4
Centre Hospitalier Affilie Universitaire de Quebec
Quebec City, Quebec, Canada, G1J1Z4
Canada
CHUM-Centre de recherche, Hôpital Notre-Dame
Montreal, Canada, H2L4M1
Germany
Klinikum Altenburger Land
Altenburg, Germany, 04600
Neurologische Klinik
Bad Neustadt, Germany, 97616
University Hospital-Dresden
Dresden, Germany, 01307
University Duesseldorf/Heinrich-Heine University
Duesseldorf, Germany, 40225
University of Erlangen
Erlangen, Germany, 91054
Alfried Krupp Hospital
Essen, Germany, 45131
University Hospital Frankfurt
Frankfurt, Germany, 60528
Freiburg University
Freiburg, Germany, 79106
Ernst-Moritz-Arndt-University Greifswald
Griefswald, Germany, 17475
Martin-Luther-Universitaet Halle-Wittenberg
Halle, Germany, 06120
University Medical Center Hamburg-Eppendorf
Hamburg, Germany, 20246
University Heidelberg
Heidelberg, Germany, 69120
Friedrich Schiller-University Jena
Jena, Germany, 07747
University Hospital Mainz
Mainz, Germany, 55131
University Hospital Muenster
Muenster, Germany, 48149
Klinikum der Universitat Muenchen
Munich, Germany, 81377
University of Ulm
Ulm, Germany, 89081
Israel
Soroka Medical Center
Beer Sheva, Israel, POB151
Rambam Medical Center
Haifa, Israel, 31096
B'nai Zion Medical Center
Haifa, Israel, 31048
Bnai-Zion Medical Center
Haifa, Israel, 31048
Wolfson Medical Center
Holon, Israel, 58100
Rabin Medical Center-Golda Campus
Petach Tikva, Israel, 49372
Sheba Medical Center
Ramat Gan, Israel, 52621
Tel Aviv Medical Center
Tel Aviv, Israel, 64239
Italy
Genoa University Hospital
Genoa, Italy, 16132
University of Laquila
Laquila, Italy, 67100
University Vita Salute San Raffaele
Milan, Italy, 20132
IRCCS FONdazione Istituto Neurologico C. Mondino
Pavia, Italy, 27100
University of Perugia
Perugia, Italy, 06100
University of Rome (S. Andrea Hospital)
Roma, Italy, 00189
Sacred Heart Catholic University
Rome, Italy, 00168
University of Rome La Sapienza
Rome, Italy, 00161
Jazzolino Hospital
Vibo Valentia, Italy, 89900
Puerto Rico
University of Puerto Rico
San Juan, Puerto Rico, 00936
United Kingdom
Royal Bournemouth
Bournemouth, Dorset, United Kingdom, BH7 7DW
Queen Elizabeth The Queen Mother Hospital
Margate, Kent, United Kingdom, CT9 4AN
Blackpool Victoria Hospital
Blackpool, Lancashire, United Kingdom, FY3 8NR
Wansbeck General Hospital
Ashington, Northumberland, United Kingdom, NE63 9JJ
Glasgow Royal Infirmary
Glasgow, Scotland, United Kingdom, G4 0SF
Southern General Hospital
Glasgow, Scotland, United Kingdom, G51 4TF
Stobhill Hospital
Glasgow, Scotland, United Kingdom, G21 3UT
Queen Elizabeth Hospital Gateshead
Gateshead, Tyne and Wear, United Kingdom, NE9 6SX
Aberdeen Royal Infirmary
Aberdeen, United Kingdom, AB25 2ZN
Monklands Hospital
Airdrie, United Kingdom, ML6 7UN
William Harvey Hospital
Ashford, United Kingdom, TN24 OLZ
Royal United Hospital
Bath, United Kingdom, BA1 3NG
Addenbrookes Foundation NHS Trust (Cambridge)
Cambridge, United Kingdom, CB2 2QQ
Countess of Chester Foundation Trust
Cheshire, United Kingdom, CH2 IUL
Dewsbury District Hospital
Dewsbury, United Kingdom, WF13 4HS
Southend University Hospital
Essex, United Kingdom, SS0 0RY
Devon PCT
Exeter, United Kingdom, EX2 5DW
Royal Devon and Exeter
Exeter, United Kingdom, EX2 5DW
Royal Surrey County Hospital
Guildford, United Kingdom, GU2 7XX
Calderdale Royal Hospital
Halifax, United Kingdom, HX3 0PW
The Royal Liverpool and Broadgreen University Hospitals
Liverpool, United Kingdom, L7 8XP
University Hospital Aintree
Liverpool, United Kingdom, L9 7AL
Kings College London
London, United Kingdom, SE5 9RS
Saint Georges University of London
London, United Kingdom, SW17 ORE
Luton and Dubstable Hospital
Luton, United Kingdom, LU4 0DZ
James Cook University Hospital
Middlesbrough, United Kingdom, TS4 3BW
Newcastle upon Tyne
Newcastle upon Tyne, United Kingdom, NE1 4LP
Torbay Hospital (South Devon Healthcare NHS Foundation Trust)
Torquay, United Kingdom, TQ2 7AA
North Tyneside General Hospital
Tyne and Wear, United Kingdom, NE29 2NH
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:
Stroke
Cerebral Infarction
Infarction
Myocardial Infarction
Insulin Resistance
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Brain Infarction
Brain Ischemia
Ischemia
Pathologic Processes
Necrosis
Myocardial Ischemia
Heart Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Pioglitazone
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 18, 2014