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Effect of Insulin Sensitizer Therapy on Atherothrombotic and Inflammatory Profiles Associated With Insulin Resistance

7 oktober 2013 bijgewerkt door: K. Sreekumaran Nair, Mayo Clinic
The objective of this study is to determine whether targeted pharmacological improvement of insulin sensitivity will normalize the associated elevations of thrombotic and inflammatory cardiovascular disease (CVD) biomarkers in individuals with insulin resistance.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

Individuals with diabetes mellitus (DM) are disproportionately affected by atherothrombotic disorders, including cardiovascular, cerebrovascular, and peripheral vascular diseases. Atherothrombotic disease risk and mortality are also increased with metabolic syndrome, a constellation of risk factors present in more than 34% of adults, even in absence of diabetes. Yet, large clinical trials of diabetes therapies have shown that conventional cardiovascular disease (CVD) risk factors, specifically hyperglycemia and hypertension, do not fully account for increased CVD risk associated with DM.

There may be an etiologic link among insulin resistance, inflammation and thrombotic events. This study seeks to determine if certain two diabetes medications (the insulin sensitizing medications) will affect certain biomarkers (or laboratory tests) for CVD in individuals with untreated DM or impaired fasting glucose.

Patients will be screened for inclusion into this this double-blinded, randomized), placebo-controlled study. If inclusion criteria are met and exclusion criteria not met, patients will be enrolled in the the study. Half of the subjects will be randomized (like the flip of a coin) to take two insulin sensitizing, anti-diabetic drugs pioglitazone (Actos) and metformin (Glucophage) taken together for three months and the other half of the subjects will take corresponding placebo (dummy) tablets.

Laboratory measurements will be obtained on the morning(s) following the two in-patient overnight stays in the Mayo Clinic Clinical Research Unit. The first stay will be at baseline and the second stay will be 3 months after baseline. Insulin sensitivity will be measured in the morning following a standardized meal the preceding night, and after an overnight fast.

The changes (from baseline to 3 months) in insulin sensitivity, glycemic control, the lipid profile, thrombotic markers and inflammatory markers will be determined and compared between the two arms of the study (placebo versus insulin sensitizing drugs).

Studietype

Ingrijpend

Inschrijving (Werkelijk)

28

Fase

  • Fase 2

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studie Locaties

  • Verenigde Staten
    • Minnesota
      • Rochester, Minnesota, Verenigde Staten, 55905
        • Mayo Clinic

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

20 jaar en ouder (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion criteria:

  • We will study 30 patients with Type 2 Diabetes or impaired fasting glucose (15 men & 15 women) who are > 20 years old.
  • Only patients who use lifestyle modification to manage their diabetes and are not on any oral hypoglycemic agents or insulin will be included.
  • We will enroll subjects who have fasting glucose concentration greater than 100 mg/dl on two consecutive occasions and have a Body Mass Index between 27-36 kg/m^2.

Exclusion Criteria:

  • We will exclude patients whose blood glucose is above 180 mg/dl. This will avoid the need to perform home glucose monitoring and the potential of unblinding the study by the volunteers.
  • Patients taking oral hypoglycemic agents or insulin would be excluded.
  • Any diseases such as active cardiovascular disease, liver diseases, kidney failure (males with serum creatinine >= 1.5mg/dl, females >=1.4 mg/dl), active endocrinopathies, debilitating chronic disease, anemia, symptoms of undiagnosed illness, history of alcoholism (alcohol use > 4oz/day) or substance abuse, chronic neurological diseases including Alzheimer's disease, stroke, etc, myopathies or any other active disease that may potentially affect the outcome measures.
  • Patients on medicines such as beta blockers, corticosteroids, tricyclics, benzodiazepines, opiates, barbiturates, anticoagulants and any other drugs or preparations that may affect mitochondrial function will be excluded.
  • People allergic to any of the class of drug such as lidocaine will also be excluded.
  • People with pacemakers, certain aneurysm clips and claustrophobia will also be excluded as they cannot undergo magnetic resonance imaging.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

  • Primair doel: Behandeling
  • Toewijzing: Gerandomiseerd
  • Interventioneel model: Parallelle opdracht
  • Masker: Dubbele

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Actieve vergelijker: Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
Geneesmiddel: metformin
To minimize side effects the metformin will be initiated at 500 mg twice daily with meals and increased to 1 gm twice daily with meals after two weeks and continue to a total of 3 months of dosing.
Andere namen:
  • Glucofaag
  • Glumetza
  • Fortamet
  • Riomet
  • Glucophage Extended Release (XR)
Geneesmiddel: pioglitazone
To minimize side effects, the pioglitazone will be initiated at 30 mg daily and increased to 45 mg daily after two weeks, and continue to a total of 3 months of dosing.
Andere namen:
  • Actos
Placebo-vergelijker: Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
Geneesmiddel: Placebo
Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
Tijdsspanne: Baseline, 3 months
Insulin sensitivity was measured the morning after an overnight fast during an in-patient stay in the Clinical Research Unit & was determined by the mean GIR necessary to maintain euglycemia during a hyperinsulinemic (1.5 mcIU/kg of FFM per minute)-euglycemic (85-95 mg/dL) clamp. The clamp is an 8 hour process where a hand vein is catheterized to collect blood samples and intravenous lines are used to infuse glucose, saline, insulin, phenylalanine and amino acid solutions at at pre-specified times/rates. The mean GIR was calculated as the rate per kilograms of fat-free mass (FFM) during 4 hours of steady-state (hours 4-8 of the 8 hour clamp) reported as micromols/kilogram of FFM per minute. The FFM was measured by dual-energy x-ray absorptiometry (DEXA) scan. Insulin was infused with 5% essential amino acid solution (3mL/kg of FFM/hour) to prevent the insulin-dependent decrease of amino acids during insulin infusion.
Baseline, 3 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change From Baseline in Fasting Blood Glucose Level
Tijdsspanne: Baseline, 3 months
Glucose (sugar) was measured in the blood and reported in milligrams per deciliter (mg/dL).
Baseline, 3 months
Change From Baseline in Glycosylated Hemoglobin (HbA1c)
Tijdsspanne: Baseline, 3 months
HbA1c is a measure of average blood sugar levels over the preceding 3 month period. HbA1c was measured by ion-exchange chromatography and reported as a percentage.
Baseline, 3 months
Change From Baseline in Insulin Levels
Tijdsspanne: Baseline, 3 months
Insulin levels in the blood were measured by immunoenzymatic assay and reported in micro International Units per milliliter (mcIU/mL).
Baseline, 3 months
Change From Baseline in Lipid Profile
Tijdsspanne: Baseline, 3 months
Change in lipids were measured by the change from baseline to 3 months of triglycerides, high-density lipoprotein cholesterol (HDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). All were reported in milligrams/deciliter (mg/dL).
Baseline, 3 months
Change From Baseline in the Thrombotic Biomarker Fibrinogen
Tijdsspanne: Baseline, 3 months
Fibrinogen was measured by thrombin clotting rate assay (Beckman Coulter, Inc. Brea, California) and reported in milligrams/deciliter (mg/dL).
Baseline, 3 months
Change From Baseline in the Thrombotic Biomarker Plasminogen Activator Inhibitor-1 (PAI-1)
Tijdsspanne: Baseline, 3 months
PAI-1 was measured by enzyme-linked immunosorbent assay (Diagnostica Stago Inc., Parsippany, New Jersey) and reported in nanograms per milliliter (ng/mL).
Baseline, 3 months
Change From Baseline in the Inflammatory Biomarker Interleukin 6 (IL-6)
Tijdsspanne: Baseline, 3 months
IL-6 is an inflammatory cytokine and reported in picograms per deciliter (pg/dL).
Baseline, 3 months
Change From Baseline in the Inflammatory Biomarker C-Reactive Protein (CRP)
Tijdsspanne: Baseline, 3 months
CRP is an inflammatory cytokine and is reported in milligrams per deciliter (mg/dL).
Baseline, 3 months
Change From Baseline in Inflammatory Biomarker Tumor Necrosis Factor-alpha (TNF-α)
Tijdsspanne: Baseline, 3 month
TNF-α is an inflammatory cytokine and is reported in picograms/milliliter (pg/mL).
Baseline, 3 month
Change From Baseline in the Inflammatory Biomarker Adiponectin
Tijdsspanne: Baseline, 3 months
Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
Baseline, 3 months

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Change From Baseline in Body Mass Index
Tijdsspanne: Baseline, 3 months
Body Mass Index (BMI) is a health index for comparing weight to height. BMI is a person's weight in kilograms (kg) divided by his or her height in meters squared. The body mass index is an indication if a person is at a suitable weight for his height on an approximation of body fat.
Baseline, 3 months
Change From Baseline in Body Fat
Tijdsspanne: Baseline, 3 months
Body fat is reported as a percentage of body weight.
Baseline, 3 months
Change From Baseline in Fat-Free Mass (FFM)
Tijdsspanne: Baseline, 3 months
FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
Baseline, 3 months

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

Mayo Clinic

Medewerkers

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Center for Research Resources (NCRR)
Takeda Pharmaceuticals North America, Inc.

Publicaties en nuttige links

De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.

Algemene publicaties

Nuttige links

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start

1 augustus 2005

Primaire voltooiing (Werkelijk)

1 augustus 2010

Studie voltooiing (Werkelijk)

1 augustus 2010

Studieregistratiedata

Eerst ingediend

26 februari 2007

Eerst ingediend dat voldeed aan de QC-criteria

5 maart 2007

Eerst geplaatst (Schatting)

6 maart 2007

Updates van studierecords

Laatste update geplaatst (Schatting)

31 oktober 2013

Laatste update ingediend die voldeed aan QC-criteria

7 oktober 2013

Laatst geverifieerd

1 oktober 2013

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • 05-004002
  • UL1RR024150 (Subsidie/contract van de Amerikaanse NIH)
  • KL2RR024151 (Subsidie/contract van de Amerikaanse NIH)
  • R01DK041973 (Subsidie/contract van de Amerikaanse NIH)

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

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