Lovaza® and Microvascular Function in Type 2 Diabetes
28 marzo 2017 aggiornato da: 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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
44
Fase
- Fase 4
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
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Virginia
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Norfolk, Virginia, Stati Uniti, 23510
- Strelitz Diabetes Center
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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
Da 18 anni a 80 anni (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- Subjects may be males or non-pregnant, non-lactating females age 18-80 years.
- Subjects must have been diagnosed with type 2 diabetes mellitus according to the current ADA criteria.
- Triglyceride levels above 149 mg/dL
- Minimum of 2 years after diagnosis of type 2 diabetes
- Prior to participation in this study, each subject must sign an informed consent document.
Exclusion Criteria:
- 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).
- Presence of diabetic retinopathy that is more severe than "background" level.
- Presence of diabetic nephropathy, defined by urine dipstick results greater than 300 mg/100 mL for protein (proteinuria).
- Presence of clinically significant neuropathy that is clearly of non-diabetic origin, e.g. alcoholic or autoimmune.
- Bilateral amputation of lower extremities or foot ulcers involving the great toes. Presence of neuroarthropathy (Charcot deformity) is allowable.
- History of major macrovascular events such as myocardial infarction or stroke.
- Participation in another clinical trial concurrently or within 30 days prior to entry into this study.
- 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.
- 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.
- Presence of pedal edema.
- Presence or history of heart failure New York Heart Association Class II or greater.
- Other serious medical conditions that in the opinion of the investigator, would compromise the subject's participation in the study.
- Concomitant use of medications known to exacerbate triglyceride levels, such as estrogens.
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: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore 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.
|
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.
|
|
Comparatore attivo: 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.
|
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.
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude.
Lasso di tempo: 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
|
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Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures.
Lasso di tempo: 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).
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One year
|
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Measurements of Indices of Large and Small Fiber Nerve Function Using Vibration and Thermal Thresholds.
Lasso di tempo: 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
Lasso di tempo: 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.
Lasso di tempo: One year
|
Oxidative stress/inflammatory markers (IL1β, IKKβ, TLR4, TNF-α, JNK1, toll-like receptor 2) were assessed through a meal challenge.
|
One year
|
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Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity.
Lasso di tempo: One Year
|
One Year
|
|
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.
Lasso di tempo: One Year
|
One Year
|
|
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction
Lasso di tempo: One Year
|
One Year
|
|
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Efficacy Measures Examining Increased Vascular Response to Ischemic Block and to Local Warming at the Dorsum of the Foot.
Lasso di tempo: One Year
|
One Year
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Aaron I Vinik, MD, PhD, Eastern Virginia Medical School
- Direttore dello studio: Henri K Parson, PhD, Eastern Virgina Medical School
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 ottobre 2009
Completamento primario (Effettivo)
1 luglio 2012
Completamento dello studio (Effettivo)
1 luglio 2012
Date di iscrizione allo studio
Primo inviato
17 giugno 2009
Primo inviato che soddisfa i criteri di controllo qualità
30 giugno 2009
Primo Inserito (Stima)
2 luglio 2009
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
9 maggio 2017
Ultimo aggiornamento inviato che soddisfa i criteri QC
28 marzo 2017
Ultimo verificato
1 marzo 2017
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- LVZ111903
Informazioni su farmaci e dispositivi, documenti di studio
Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti
No
Studia un dispositivo regolamentato dalla FDA degli Stati Uniti
No
prodotto fabbricato ed esportato dagli Stati Uniti
No
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 .