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

7 ottobre 2013 aggiornato da: 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.

Panoramica dello studio

Stato

Completato

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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).

Tipo di studio

Interventistico

Iscrizione (Effettivo)

28

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Luoghi di studio

  • Stati Uniti
    • Minnesota
      • Rochester, Minnesota, Stati Uniti, 55905
        • Mayo Clinic

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

20 anni e precedenti (Adulto, Adulto più anziano)

Accetta volontari sani

No

Sessi ammissibili allo studio

Tutto

Descrizione

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.

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione parallela
  • Mascheramento: Doppio

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Insulin Sensitizer Therapy
Two insulin sensitizing drugs will be taken together for 3 months; metformin 1000 mg twice daily plus pioglitazone 45 mg daily.
Droga: 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.
Altri nomi:
  • Glucofago
  • Glumetz
  • Fortamet
  • Riomet
  • Glucophage Extended Release (XR)
Droga: 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.
Altri nomi:
  • Atto
Comparatore placebo: Placebo
Placebo tablets were used to match the active comparator drugs and dosing regimen.
Droga: Placebo
Placebo tablets matching the metformin and pioglitazone tablets are given in the same regimen as the active drug arm for 3 months.

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change From Baseline in Insulin Sensitivity as Measured by Glucose Infusion Rate (GIR)
Lasso di tempo: 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

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Change From Baseline in Fasting Blood Glucose Level
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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)
Lasso di tempo: 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
Lasso di tempo: Baseline, 3 months
Adiponectin is an anti-inflammatory cytokine and is reported in milligrams per milliliter (mg/mL).
Baseline, 3 months

Altre misure di risultato

Misura del risultato
Misura Descrizione
Lasso di tempo
Change From Baseline in Body Mass Index
Lasso di tempo: 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
Lasso di tempo: Baseline, 3 months
Body fat is reported as a percentage of body weight.
Baseline, 3 months
Change From Baseline in Fat-Free Mass (FFM)
Lasso di tempo: Baseline, 3 months
FFM was measured using dual energy x-ray absorptiometry (DEXA) scans and is reported in kilograms (kg).
Baseline, 3 months

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Mayo Clinic

Collaboratori

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

Pubblicazioni e link utili

La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.

Pubblicazioni generali

Collegamenti utili

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio

1 agosto 2005

Completamento primario (Effettivo)

1 agosto 2010

Completamento dello studio (Effettivo)

1 agosto 2010

Date di iscrizione allo studio

Primo inviato

26 febbraio 2007

Primo inviato che soddisfa i criteri di controllo qualità

5 marzo 2007

Primo Inserito (Stima)

6 marzo 2007

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Stima)

31 ottobre 2013

Ultimo aggiornamento inviato che soddisfa i criteri QC

7 ottobre 2013

Ultimo verificato

1 ottobre 2013

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • 05-004002
  • UL1RR024150 (Sovvenzione/contratto NIH degli Stati Uniti)
  • KL2RR024151 (Sovvenzione/contratto NIH degli Stati Uniti)
  • R01DK041973 (Sovvenzione/contratto NIH degli Stati Uniti)

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

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