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Lovaza® and Microvascular Function in Type 2 Diabetes

28 maart 2017 bijgewerkt door: Aaron I. Vinik, MD, PhD, Eastern Virginia Medical School

The Role of Lovaza® on Microvascular Function and Lipoprotein Profile in Type 2 Diabetes

The objective of this study is to determine the efficacy of 6 months of 4 g/day oral Lovaza® on endothelial-dependent and heat-induced vasodilation in type 2 diabetics with neuropathy and elevated triglyceride levels. Omega-3 fatty acids appear to exert beneficial effects on vascular function that are independent of the changes in serum triglycerides. The efficacy will be compared with a placebo given at the same duration. Efficacy of the drug will be evaluated after 3 and 6 months of treatment. This timeline should be adequate for evaluation of the primary neurophysiological endpoints. Previously, the investigators have demonstrated that it is feasible to pharmacologically alter nerve fiber density in as little as 18 weeks and that this correlates with subjective and objective measures of neurovascular function. The investigators are predicting an enhancement of post-ischemic hyperemia of the foot dorsum, where the dilative mechanism is primarily endothelium-dependent and a similar improvement in heat-induced hyperemia.

Studie Overzicht

Toestand

Voltooid

Conditie

Interventie / Behandeling

Gedetailleerde beschrijving

This pilot study is a within-subject repeated measures design. This study will compare the neurophysiological and vascular responses to placebo and treatment with Lovaza® (omega-3-acid ethyl esters, Reliant Pharmaceuticals, Inc.) in subjects with type 2 diabetes, neuropathy, and dyslipidemia.

Lovaza's potential mechanism of action is the inhibition of acyl Coenzyme A:1, 2-diacylglycerol acyltransferase and increased peroxisomal β-oxidation in the liver.

Subjects will be recruited and a baseline of physiological, neurological and hematological profile established for each patient. Forty-four subjects (20 in the active arm, 20 in the placebo arm, and 2 replacements for each arm) will receive 4 g/day Lovaza® tablets or placebo for a period of 6 months. All subjects will receive a physical and neurological exam as well as neurovascular function testing. This includes nerve conduction studies, quantitative sensory testing, quantitative autonomic testing, and skin blood flow testing, which includes, ischemia reperfusion. Lab tests include an insulin resistance profile, hepatic and renal function profiles, lipid profile, C-reactive protein, thyroid stimulating hormone, and fatty acids. Other tests include inflammatory markers such as adiponectin and tumor necrosis factor-α. The study is powered to detect differences in microvascular function after 6 months of Lovaza® and differences in ethnic responses.

Studietype

Ingrijpend

Inschrijving (Werkelijk)

44

Fase

  • Fase 4

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
    • Virginia
      • Norfolk, Virginia, Verenigde Staten, 23510
        • Strelitz Diabetes Center

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

18 jaar tot 80 jaar (Volwassen, Oudere volwassene)

Accepteert gezonde vrijwilligers

Nee

Geslachten die in aanmerking komen voor studie

Allemaal

Beschrijving

Inclusion Criteria:

  1. Subjects may be males or non-pregnant, non-lactating females age 18-80 years.
  2. Subjects must have been diagnosed with type 2 diabetes mellitus according to the current ADA criteria.
  3. Triglyceride levels above 149 mg/dL
  4. Minimum of 2 years after diagnosis of type 2 diabetes
  5. Prior to participation in this study, each subject must sign an informed consent document.

Exclusion Criteria:

  1. Presence of type 1 diabetes mellitus (defined as C-peptide < 1 ng/ml or diabetes onset at < 35 years of age in a non-obese patient).
  2. Presence of diabetic retinopathy that is more severe than "background" level.
  3. Presence of diabetic nephropathy, defined by urine dipstick results greater than 300 mg/100 mL for protein (proteinuria).
  4. Presence of clinically significant neuropathy that is clearly of non-diabetic origin, e.g. alcoholic or autoimmune.
  5. Bilateral amputation of lower extremities or foot ulcers involving the great toes. Presence of neuroarthropathy (Charcot deformity) is allowable.
  6. History of major macrovascular events such as myocardial infarction or stroke.
  7. Participation in another clinical trial concurrently or within 30 days prior to entry into this study.
  8. The use of ACE-inhibiting agents or angiotensin receptor blockade therapy (ARB) is allowed but must have been stable for at least 30 days prior to study entry and may not change during the course of the study. This is prudent due to their potential effects on blood flow.
  9. Patients with moderate or severe hepatic insufficiency or abnormalities of liver function defined as any liver enzymes (aspartate aminotransferase,alanine transaminase, alkaline phosphatase) greater than 3 times the upper limit of normal.
  10. Presence of pedal edema.
  11. Presence or history of heart failure New York Heart Association Class II or greater.
  12. Other serious medical conditions that in the opinion of the investigator, would compromise the subject's participation in the study.
  13. Concomitant use of medications known to exacerbate triglyceride levels, such as estrogens.

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: Verdrievoudigen

Wapens en interventies

Deelnemersgroep / Arm
Interventie / Behandeling
Placebo-vergelijker: Placebo
Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking placebo for 6 months.
Geneesmiddel: Placebo
Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking placebo for 6 months.
Actieve vergelijker: omega-3-ethyl esters 4g
Subjects are males or non-pregnant, non-lactating females age 18-80 years. All subjects must have been diagnosed with type 2 diabetes mellitus a minimum of two years according to the current ADA criteria and triglyceride levels above 149 mg/dL. Subjects in this arm will be taking 4 g of Lovaza per day for 6 months.
Geneesmiddel: omega-3-ethyl esters
Lovaza (TM) (omega-3-ethyl esters) 1 gram Capsules are indicated as an adjunct to diet to reduce very high (>500 mg/dL) triglyceride (TG) levels in adult patients.
Andere namen:
  • Lovaza

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude.
Tijdsspanne: One year
19 participants in each arm( placebo or omega-3-ethyl esters 4g) were analyzed . Conduction velocities and amplitude of the following nerves were compared between each arm: Tibial Nerve Ankle Amplitude, Tibial Nerve Popliteal Amplitude, Median Nerve Wrist Amplitude, Median Nerve Elbow Amplitude, Peroneal Motor Nerve Ankle Amplitude, Peroneal Motor Nerve Below Fibular Amplitude, Peroneal Motor Nerve Above Fibular Amplitude, Sensory Median Nerve Wrist Amplitude, Sensory Ulnar, Sensory Sural Ankle Ampltiude Wrist Ampltiude
One year
Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures.
Tijdsspanne: One year
Quantitative Autonomic Function Tests (QAFTs) were performed. Primarily, power spectral analysis of heart rate variability (HRV) and time- and frequency-domain analyses, including measures of the sympathetic and parasympathetic control of the heart beat (R-R interval), were recorded with deep breathing, Valsalva, and standing from the sitting position maneuvers. Additionally, the sample difference of the beat to beat (NN) intervals and the TSP was calculated as well as the standard deviation of all normal R-R intervals (sdNN).
One year
Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds.
Tijdsspanne: One year
Quantitative Sensory Tests (QSTs), including, cold sensation threshold, cold pain threshold and vibration detection threshold, were used to evaluate peripheral sensory perception.
One year
Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds
Tijdsspanne: One year
Quantitative Sensory Tests (QSTs), including vibration detection threshold, were used to evaluate peripheral sensory perception. Mean represents percent change of total group. Measurements taken at baseline and at one year.
One year
Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress.
Tijdsspanne: One year
Oxidative stress/inflammatory markers (IL1β, IKKβ, TLR4, TNF-α, JNK1, toll-like receptor 2) were assessed through a meal challenge.
One year
Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity.
Tijdsspanne: One Year
One Year
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.
Tijdsspanne: One Year
One Year
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction
Tijdsspanne: One Year
One Year
Efficacy Measures Examining Increased Vascular Response to Ischemic Block and to Local Warming at the Dorsum of the Foot.
Tijdsspanne: One Year
One Year

Medewerkers en onderzoekers

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

Sponsor

Eastern Virginia Medical School

Medewerkers

GlaxoSmithKline

Onderzoekers

  • Hoofdonderzoeker: Aaron I Vinik, MD, PhD, Eastern Virginia Medical School
  • Studie directeur: Henri K Parson, PhD, Eastern Virgina Medical School

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 oktober 2009

Primaire voltooiing (Werkelijk)

1 juli 2012

Studie voltooiing (Werkelijk)

1 juli 2012

Studieregistratiedata

Eerst ingediend

17 juni 2009

Eerst ingediend dat voldeed aan de QC-criteria

30 juni 2009

Eerst geplaatst (Schatting)

2 juli 2009

Updates van studierecords

Laatste update geplaatst (Werkelijk)

9 mei 2017

Laatste update ingediend die voldeed aan QC-criteria

28 maart 2017

Laatst geverifieerd

1 maart 2017

Meer informatie

Termen gerelateerd aan deze studie

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • LVZ111903

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

product vervaardigd in en geëxporteerd uit de V.S.

Nee

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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