Insulin Resistance Intervention After Stroke Trial (IRIS)

Insulin Resistance Intervention After Stroke (IRIS) Trial

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.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Stroke; Diabetes
• Intervention / Treatment: Drug: pioglitazone; Drug: placebo

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 Type: Interventional
• Enrollment (Actual): 3876
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Bedford Park, New South Wales, Australia, 5042
      • Flinders Medical Centre
    • Camperstown, New South Wales, Australia, 2050
      • Royal Prince Alfred
    • New Lambton Heights, New South Wales, Australia, 2305
      • John Hunter Hospital (University of Newcastle)
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital (Eastern Health)
    • Footscray, Victoria, Australia, 3011
      • Western Hospital (University of Melbourne)
    • Heidelberg Heights, Victoria, Australia, 3801
      • Austin Health (National Stroke Research Institute)
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
  • Western Australia
    • Perth, Western Australia, Australia, 6000
      • Royal Perth
• Canada
  • Montreal, Canada, H2L4M1
    • CHUM-Centre de recherche, Hôpital Notre-Dame
  • Alberta
    • Edmonton, Alberta, Canada, T6G2B7
      • University of Alberta
    • Lethbridge, Alberta, Canada, T1J0N9
      • Center for Neurologic Research
  • British Columbia
    • Victoria, British Columbia, Canada, V8R4R2
      • Vancouver Island Health Research Centre
  • Ontario
    • London, Ontario, Canada, N6G2V2
      • Robarts Research Institute
    • Ottawa, Ontario, Canada, K1Y 4E9
      • Ottawa Hospital-General Campus
    • Thunder Bay, Ontario, Canada, P7B7C7
      • Intermountain Research Consultants
    • Toronto, Ontario, Canada, M5B1W8
      • St. Michael's Hospital
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
      • Hopital Charles LeMoyne
    • Montreal, Quebec, Canada, H3G1A4
      • McGill-Montreal General
    • Montreal, Quebec, Canada, H3T1E2
      • McGill-Jewish General
    • Quebec City, Quebec, Canada, G1J1Z4
      • Centre hospitalier affilié universitaire de Québec
• Germany
  • Altenburg, Germany, 04600
    • Klinikum Altenburger Land
  • Bad Neustadt, Germany, 97616
    • Neurologische Klinik
  • Dresden, Germany, 01307
    • University Hospital-Dresden
  • Duesseldorf, Germany, 40225
    • University Duesseldorf/Heinrich-Heine University
  • Erlangen, Germany, 91054
    • University of Erlangen
  • Essen, Germany, 45131
    • Alfried Krupp Hospital
  • Frankfurt, Germany, 60528
    • University Hospital Frankfurt
  • Freiburg, Germany, 79106
    • Freiburg University
  • Griefswald, Germany, 17475
    • Ernst-Moritz-Arndt-University Greifswald
  • Halle, Germany, 06120
    • Martin-Luther-Universitaet Halle-Wittenberg
  • Hamburg, Germany, 20246
    • University Medical Center Hamburg-Eppendorf
  • Heidelberg, Germany, 69120
    • University Heidelberg
  • Jena, Germany, 07747
    • Friedrich Schiller-University Jena
  • Mainz, Germany, 55131
    • University Hospital Mainz
  • Muenster, Germany, 48149
    • University hospital Muenster
  • Munich, Germany, 81377
    • Klinikum der Universitat Muenchen
  • Ulm, Germany, 89081
    • University of Ulm
• Israel
  • Beer Sheva, Israel, POB151
    • Soroka Medical Center
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 31048
    • B'nai Zion Medical Center
  • Haifa, Israel, 31048
    • Bnai-Zion Medical Center
  • Holon, Israel, 58100
    • Wolfson Medical Center
  • Petach Tikva, Israel, 49372
    • Rabin Medical Center-Golda Campus
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Medical Center
• Italy
  • Genoa, Italy, 16132
    • Genoa University Hospital
  • Laquila, Italy, 67100
    • University of Laquila
  • Milan, Italy, 20132
    • University Vita Salute San Raffaele
  • Pavia, Italy, 27100
    • IRCCS Fondazione Istituto Neurologico C. Mondino
  • Perugia, Italy, 06100
    • University Of Perugia
  • Roma, Italy, 00189
    • University of Rome (S. Andrea Hospital)
  • Rome, Italy, 00168
    • Sacred Heart Catholic University
  • Rome, Italy, 00161
    • University of Rome La Sapienza
  • Vibo Valentia, Italy, 89900
    • Jazzolino Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • University of Puerto Rico
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Airdrie, United Kingdom, ML6 7UN
    • Monklands Hospital
  • Ashford, United Kingdom, TN24 OLZ
    • William Harvey Hospital
  • Bath, United Kingdom, BA1 3NG
    • Royal United Hospital
  • Cambridge, United Kingdom, CB2 2QQ
    • Addenbrookes Foundation NHS Trust (Cambridge)
  • Cheshire, United Kingdom, CH2 IUL
    • Countess of Chester Foundation Trust
  • Dewsbury, United Kingdom, WF13 4HS
    • Dewsbury District Hospital
  • Essex, United Kingdom, SS0 0RY
    • Southend University Hospital
  • Exeter, United Kingdom, EX2 5DW
    • Devon PCT
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter
  • Guildford, United Kingdom, GU2 7XX
    • Royal Surrey County Hospital
  • Halifax, United Kingdom, HX3 0PW
    • Calderdale Royal Hospital
  • Liverpool, United Kingdom, L7 8XP
    • The Royal Liverpool and Broadgreen University Hospitals
  • Liverpool, United Kingdom, L9 7AL
    • University Hospital Aintree
  • London, United Kingdom, SE5 9RS
    • Kings College London
  • London, United Kingdom, SW17 ORE
    • Saint Georges University of London
  • Luton, United Kingdom, LU4 0DZ
    • Luton and Dubstable Hospital
  • Middlesbrough, United Kingdom, TS4 3BW
    • James Cook University Hospital
  • Newcastle upon Tyne, United Kingdom, NE1 4LP
    • Newcastle upon Tyne
  • Torquay, United Kingdom, TQ2 7AA
    • Torbay Hospital (South Devon Healthcare NHS Foundation Trust)
  • Tyne And Wear, United Kingdom, NE29 2NH
    • North Tyneside General Hospital
  • Dorset
    • Bournemouth, Dorset, United Kingdom, BH7 7DW
      • Royal Bournemouth
  • Kent
    • Margate, Kent, United Kingdom, CT9 4AN
      • Queen Elizabeth the Queen Mother Hospital
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY3 8NR
      • Blackpool Victoria Hospital
  • Northumberland
    • Ashington, Northumberland, United Kingdom, NE63 9JJ
      • Wansbeck General Hospital
  • Scotland
    • Glasgow, Scotland, United Kingdom, G51 4TF
      • Southern General Hospital
    • Glasgow, Scotland, United Kingdom, G21 3UT
      • Stobhill Hospital
    • Glasgow, Scotland, United Kingdom, G4 0SF
      • Glasgow Royal Infirmary
  • Tyne And Wear
    • Gateshead, Tyne And Wear, United Kingdom, NE9 6SX
      • Queen Elizabeth Hospital Gateshead
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-0007
      • University of Alabama
    • Mobile, Alabama, United States, 36617-2293
      • University of South Alabama
  • Arizona
    • Tucson, Arizona, United States, 85721-5023
      • University of Arizona
  • California
    • Colton, California, United States, 92324
      • Shanti Clinical Trials (NINDS-CRC site)
    • Fresno, California, United States, 93702
      • UCSF-Fresno
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Los Angeles, California, United States, 90095
      • University of California
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95817
      • University of California-Davis
    • San Diego, California, United States, 92103-8466
      • University of California
    • San Francisco, California, United States, 94143-0114
      • University of California
  • Colorado
    • Denver, Colorado, United States, 80204-4507
      • Denver Health and Hospital Authority
  • Connecticut
    • Hartford, Connecticut, United States, 06102-5037
      • Hartford
    • New Haven, Connecticut, United States, 06519
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20010-2949
      • National Rehabilitation Hospital
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida
    • Melbourne, Florida, United States, 32901
      • MIMA Century Research Associates
    • Pembroke Pines, Florida, United States, 33026
      • Pines Neurological Associates (NINDS-CRC site)
    • Tampa, Florida, United States, 33606-3500
      • Floria Neurovascular Institute
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University
    • Chicago, Illinois, United States, 60612
      • Cook County (Stroger) Hospital
    • Harvey, Illinois, United States, 60426
      • Ingalls Memorial Hospital (NINDS-CRC site)
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Peoria, Illinois, United States, 61637-0001
      • OSF St. Francis Medical Center
    • Saint Charles, Illinois, United States, 60175
      • Tri-City Neruology (NINDS-CRC site)
  • Indiana
    • Elkhart, Indiana, United States, 46514
      • Indiana Medical Research
    • Valparaiso, Indiana, United States, 46383
      • Associates In Neurology (NINDS-CRC site)
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Iowa Health Des Moines Clinical Trials Office
    • Des Moines, Iowa, United States, 50314
      • Ruan Neuroscience Center/Mercy Medical Center
    • Iowa City, Iowa, United States, 52246
      • University of Iowa
    • Waterloo, Iowa, United States, 50702
      • Northeast Iowa Medical Education Foundation (NINDS-CRC site)
  • Kansas
    • Wichita, Kansas, United States, 67214
      • Via Christi Regional Medical Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • University of Kentucky Research Foundation
  • Louisiana
    • Shreveport, Louisiana, United States, 71130-3932
      • Louisiana State University Health Sciences Center
  • Maine
    • Rockport, Maine, United States, 04856
      • Penobscot Bay Neurology
  • Maryland
    • Baltimore, Maryland, United States, 21209
      • Sinai Hospital of Baltimore
    • Baltimore, Maryland, United States, 21287-6953
      • Johns Hopkins
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University
    • Boston, Massachusetts, United States, 02114-2695
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02190
      • Caritas St. Elizabeth's Medical Center
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • East Lansing, Michigan, United States, 48824
      • Michigan State University
  • Minnesota
    • Robbinsdale, Minnesota, United States, 55426
      • Minneapolis Clinic of Neurology
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic (NINDS-CRC site)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • St. Luke's Brain and Stroke Institute
    • Saint Louis, Missouri, United States, 63110
      • Washington University
    • Saint Louis, Missouri, United States, 63141
      • St. John's Mercy Medical Center
    • Saint Louis, Missouri, United States, 63220
      • St. Louis University
  • Montana
    • Billings, Montana, United States, 59101
      • Billings Clinic
    • Great Falls, Montana, United States, 59405
      • Advanced Neurology Specialists
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Camden, New Jersey, United States, 08013
      • Cooper University Hospital
    • West Orange, New Jersey, United States, 07052
      • Kessler Medical Rehab Research Corp
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • University of New Mexico
  • New York
    • Albany, New York, United States, 12208
      • Albany Medical Center
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Brooklyn, New York, United States, 11203
      • SUNY Downstate
    • Buffalo, New York, United States, 14209
      • SUNY Buffalo
    • New York, New York, United States, 10021
      • Cornell University
    • New York, New York, United States, 10011
      • St. Vincent's Hospital Manhattan
    • Rochester, New York, United States, 14642
      • University of Rochester
    • West Seneca, New York, United States, 14224
      • Southtowns Neurology of WNY (NINDS-CRC site)
    • White Plains, New York, United States, 10605
      • Burke Medical Research Institute
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Research of Winston-Salem
    • Winston-Salem, North Carolina, United States, 27103
      • Guilford Neurologic Associates
  • North Dakota
    • Grand Forks, North Dakota, United States, 58201
      • Altru Health System
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0525
      • University of Cincinnati
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106-4938
      • Case Western Reserve University
    • Cleveland, Ohio, United States, 44109-1998
      • MetroHealth Medical Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University
    • Toledo, Ohio, United States, 43614
      • University of Toledo
  • Oregon
    • Portland, Oregon, United States, 97239-3098
      • Oregon Health & Science University
  • Pennsylvania
    • Abington, Pennsylvania, United States, 19001
      • Abington Memorial Hospital
    • Bryn Mawr, Pennsylvania, United States, 19010
      • Lankenau Institute for Medical Research
    • Hershey, Pennsylvania, United States, 17033
      • Penn Stat-Hershey Medical Center (NINDS-CRC site)
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University
    • Philadelphia, Pennsylvania, United States, 19107-5083
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15213-2582
      • University of Pittsburgh
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Singer Research Institute
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Rhode Island Hospital
  • Tennessee
    • Memphis, Tennessee, United States, 38163
      • University of Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Research Institute
    • Dallas, Texas, United States, 75390-8897
      • University of Texas, Southwestern
    • Houston, Texas, United States, 77030
      • Methodist Neurological Institute
    • San Antonio, Texas, United States, 78229-3900
      • University of Texas
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah
  • Vermont
    • Burlington, Vermont, United States, 05405
      • University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Norfolk, Virginia, United States, 23507
      • Sentara Medical Group
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic
    • Milwaukee, Wisconsin, United States, 53226-3596
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Pioglitazone; pioglitazone	Drug: pioglitazone; a thiazolidinedione drug
Placebo Comparator: Placebo; inactive substance	Drug: placebo; an inactive substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Recurrent Fatal or Non-fatal Stroke, or Fatal or Non-fatal Myocardial Infarction	Up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatal or Non-fatal Stroke Alone		5 years
Acute Coronary Syndrome	Fatal or non-fatal acute myocardial infarction or unstable angina	5 years
Development of Overt Diabetes		5 years
All Cause Mortality		5 years
Decline in Cognitive Status	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.	Annual measures from baseline to exit (up to 5 years)
Composite Outcome of Fatal or Non-fatal Stroke, Fatal or Non-fatal MI or Episode of Serious Congestive Heart Failure		5 years

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS); Takeda Pharmaceuticals North America, Inc.
• Investigators: Principal Investigator: Walter N. Kernan, M.D., Yale University

Publications and helpful links

General Publications

• Viscoli CM, Brass LM, Carolei A, Conwit R, Ford GA, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Lovejoy AM, Parsons MW, Peduzzi PN, Ringleb PA, Schwartz GG, Spence JD, Tanne D, Young LH, Kernan WN; IRIS Trial investigators. Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Am Heart J. 2014 Dec;168(6):823-9.e6. doi: 10.1016/j.ahj.2014.07.016. Epub 2014 Jul 28.
• Kernan WN, Viscoli CM, Demarco D, Mendes B, Shrauger K, Schindler JL, McVeety JC, Sicklick A, Moalli D, Greco P, Bravata DM, Eisen S, Resor L, Sena K, Story D, Brass LM, Furie KL, Gutmann L, Hinnau E, Gorman M, Lovejoy AM, Inzucchi SE, Young LH, Horwitz RI; IRIS Trial Investigators. Boosting enrollment in neurology trials with Local Identification and Outreach Networks (LIONs). Neurology. 2009 Apr 14;72(15):1345-51. doi: 10.1212/WNL.0b013e3181a0fda3.
• Kernan W, Viscoli C, Brass L, Amatangelo M, Birch A, Clark W, Conwit R, Furie K, Gorman M, Pesapane B, Kleindorfer D, Lovejoy A, Osborne J, Silliman S, Zweifler R, Horwitz R. Boosting enrolment in clinical trials: validation of a regional network model. Clin Trials. 2011 Oct;8(5):645-53. doi: 10.1177/1740774511414925. Epub 2011 Aug 8.
• Spence JD, Viscoli CM, Inzucchi SE, Dearborn-Tomazos J, Ford GA, Gorman M, Furie KL, Lovejoy AM, Young LH, Kernan WN; IRIS Investigators. Pioglitazone Therapy in Patients With Stroke and Prediabetes: A Post Hoc Analysis of the IRIS Randomized Clinical Trial. JAMA Neurol. 2019 May 1;76(5):526-535. doi: 10.1001/jamaneurol.2019.0079. Erratum In: JAMA Neurol. 2019 Mar 18;:
• Young LH, Viscoli CM, Schwartz GG, Inzucchi SE, Curtis JP, Gorman MJ, Furie KL, Conwit R, Spatz ES, Lovejoy A, Abbott JD, Jacoby DL, Kolansky DM, Ling FS, Pfau SE, Kernan WN; IRIS Investigators. Heart Failure After Ischemic Stroke or Transient Ischemic Attack in Insulin-Resistant Patients Without Diabetes Mellitus Treated With Pioglitazone. Circulation. 2018 Sep 18;138(12):1210-1220. doi: 10.1161/CIRCULATIONAHA.118.034763.
• Yaghi S, Furie KL, Viscoli CM, Kamel H, Gorman M, Dearborn J, Young LH, Inzucchi SE, Lovejoy AM, Kasner SE, Conwit R, Kernan WN; IRIS Trial Investigators. Pioglitazone Prevents Stroke in Patients With a Recent Transient Ischemic Attack or Ischemic Stroke: A Planned Secondary Analysis of the IRIS Trial (Insulin Resistance Intervention After Stroke). Circulation. 2018 Jan 30;137(5):455-463. doi: 10.1161/CIRCULATIONAHA.117.030458. Epub 2017 Oct 30.
• Kernan WN, Viscoli CM, Dearborn JL, Kent DM, Conwit R, Fayad P, Furie KL, Gorman M, Guarino PD, Inzucchi SE, Stuart A, Young LH; Insulin Resistance Intervention After Stroke (IRIS) Trial Investigators. Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction. JAMA Neurol. 2017 Nov 1;74(11):1319-1327. doi: 10.1001/jamaneurol.2017.2136.
• Stuart AC, Sico JJ, Viscoli CM, Tayal AH, Inzucchi SE, Ford GA, Furie KL, Cote R, Spence JD, Tanne D, Kernan WN. Taking care of volunteers in a stroke trial: a new assisted-management strategy. Stroke Vasc Neurol. 2016 Oct 25;1(3):108-114. doi: 10.1136/svn-2016-000029. eCollection 2016 Sep.
• Furie KL, Viscoli CM, Gorman M, Ford GA, Young LH, Inzucchi SE, Guarino PD, Lovejoy AM, Conwit R, Tanne D, Kernan WN; IRIS Trial Investigators. Effects of pioglitazone on cognitive function in patients with a recent ischaemic stroke or TIA: a report from the IRIS trial. J Neurol Neurosurg Psychiatry. 2018 Jan;89(1):21-27. doi: 10.1136/jnnp-2017-316361. Epub 2017 Sep 22.
• Young LH, Viscoli CM, Curtis JP, Inzucchi SE, Schwartz GG, Lovejoy AM, Furie KL, Gorman MJ, Conwit R, Abbott JD, Jacoby DL, Kolansky DM, Pfau SE, Ling FS, Kernan WN; IRIS Investigators. Cardiac Outcomes After Ischemic Stroke or Transient Ischemic Attack: Effects of Pioglitazone in Patients With Insulin Resistance Without Diabetes Mellitus. Circulation. 2017 May 16;135(20):1882-1893. doi: 10.1161/CIRCULATIONAHA.116.024863. Epub 2017 Feb 28.
• Viscoli CM, Inzucchi SE, Young LH, Insogna KL, Conwit R, Furie KL, Gorman M, Kelly MA, Lovejoy AM, Kernan WN; IRIS Trial Investigators. Pioglitazone and Risk for Bone Fracture: Safety Data From a Randomized Clinical Trial. J Clin Endocrinol Metab. 2017 Mar 1;102(3):914-922. doi: 10.1210/jc.2016-3237.
• Inzucchi SE, Viscoli CM, Young LH, Furie KL, Gorman M, Lovejoy AM, Dagogo-Jack S, Ismail-Beigi F, Korytkowski MT, Pratley RE, Schwartz GG, Kernan WN; IRIS Trial Investigators. Pioglitazone Prevents Diabetes in Patients With Insulin Resistance and Cerebrovascular Disease. Diabetes Care. 2016 Oct;39(10):1684-92. doi: 10.2337/dc16-0798. Epub 2016 Jul 27.
• Kernan WN, Viscoli CM, Furie KL, Young LH, Inzucchi SE, Gorman M, Guarino PD, Lovejoy AM, Peduzzi PN, Conwit R, Brass LM, Schwartz GG, Adams HP Jr, Berger L, Carolei A, Clark W, Coull B, Ford GA, Kleindorfer D, O'Leary JR, Parsons MW, Ringleb P, Sen S, Spence JD, Tanne D, Wang D, Winder TR; IRIS Trial Investigators. Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. N Engl J Med. 2016 Apr 7;374(14):1321-31. doi: 10.1056/NEJMoa1506930. Epub 2016 Feb 17.
• Kernan WN, Inzucchi SE. Metabolic rehabilitation: science gathers to support a new intervention to prevent stroke. Stroke. 2011 Dec;42(12):3333-5. doi: 10.1161/STROKEAHA.111.632489. Epub 2011 Oct 13. No abstract available. Erratum In: Stroke. 2012 Mar;43(3):e36.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: September 20, 2004
• First Submitted That Met QC Criteria: September 21, 2004
• First Posted (Estimate): September 22, 2004

Study Record Updates

• Last Update Posted (Actual): April 27, 2020
• Last Update Submitted That Met QC Criteria: April 14, 2020
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; stroke; insulin resistance; pioglitazone; heart attack
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hyperinsulinism; Myocardial Infarction; Infarction; Stroke; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 0201013034; 5U01NS044876-10 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes