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Lovaza® and Microvascular Function in Type 2 Diabetes

28 mars 2017 mis à jour par: 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.

Aperçu de l'étude

Statut

Complété

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Réel)

44

Phase

  • Phase 4

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Lieux d'étude

  • États-Unis
    • Virginia
      • Norfolk, Virginia, États-Unis, 23510
        • Strelitz Diabetes Center

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans à 80 ans (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Tripler

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: 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.
Médicament: 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.
Comparateur actif: 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.
Médicament: 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.
Autres noms:
  • Lovaza

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude.
Délai: 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.
Délai: 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.
Délai: 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
Délai: 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.
Délai: 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.
Délai: One Year
One Year
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.
Délai: One Year
One Year
Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction
Délai: One Year
One Year
Efficacy Measures Examining Increased Vascular Response to Ischemic Block and to Local Warming at the Dorsum of the Foot.
Délai: One Year
One Year

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Eastern Virginia Medical School

Collaborateurs

GlaxoSmithKline

Les enquêteurs

  • Chercheur principal: Aaron I Vinik, MD, PhD, Eastern Virginia Medical School
  • Directeur d'études: Henri K Parson, PhD, Eastern Virgina Medical School

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude

1 octobre 2009

Achèvement primaire (Réel)

1 juillet 2012

Achèvement de l'étude (Réel)

1 juillet 2012

Dates d'inscription aux études

Première soumission

17 juin 2009

Première soumission répondant aux critères de contrôle qualité

30 juin 2009

Première publication (Estimation)

2 juillet 2009

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

9 mai 2017

Dernière mise à jour soumise répondant aux critères de contrôle qualité

28 mars 2017

Dernière vérification

1 mars 2017

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • LVZ111903

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Non

Étudie un produit d'appareil réglementé par la FDA américaine

Non

produit fabriqué et exporté des États-Unis.

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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