Lovaza® and Microvascular Function in Type 2 Diabetes
2017年3月28日 更新者：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.
調査の概要
詳細な説明
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.
研究の種類
介入
入学 (実際)
44
段階
- フェーズ 4
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Virginia
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Norfolk、Virginia、アメリカ、23510
- Strelitz Diabetes Center
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年～80年 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：トリプル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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プラセボコンパレーター：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.
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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.
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アクティブコンパレータ：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.
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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.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Conduction Amplitude.
時間枠：One year
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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
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One year
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Measurements of Indices of Large and Small Fiber Nerve Function Including Heart Rate Variation Measures.
時間枠：One year
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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.
時間枠：One year
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Quantitative Sensory Tests (QSTs), including, cold sensation threshold, cold pain threshold and vibration detection threshold, were used to evaluate peripheral sensory perception.
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One year
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Percent Change in Measurements of Indices of Large and Small Fiber Nerve Function Including Vibration Thresholds
時間枠：One year
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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.
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One year
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Measurements of Indices of Large and Small Fiber Nerve Function Including Markers of Inflammation and Oxidative Stress.
時間枠：One year
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Oxidative stress/inflammatory markers (IL1β, IKKβ, TLR4, TNF-α, JNK1, toll-like receptor 2) were assessed through a meal challenge.
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One year
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Efficacy Measures Are Nerve Conduction Studies; Specifically, Increases in Conduction Velocity.
時間枠：One Year
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One Year
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in Latency.
時間枠：One Year
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One Year
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Efficacy Measures Are Nerve Conduction Studies, Specifically Changes in F-wave Conduction
時間枠：One Year
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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.
時間枠：One Year
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One Year
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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
協力者
捜査官
- 主任研究者：Aaron I Vinik, MD, PhD、Eastern Virginia Medical School
- スタディディレクター：Henri K Parson, PhD、Eastern Virgina Medical School
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始
2009年10月1日
一次修了 (実際)
2012年7月1日
研究の完了 (実際)
2012年7月1日
試験登録日
最初に提出
2009年6月17日
QC基準を満たした最初の提出物
2009年6月30日
最初の投稿 (見積もり)
2009年7月2日
学習記録の更新
投稿された最後の更新 (実際)
2017年5月9日
QC基準を満たした最後の更新が送信されました
2017年3月28日
最終確認日
2017年3月1日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
Placeboの臨床試験
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Palacky University完了
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Universidade Federal do ParaConselho Nacional de Desenvolvimento Científico e Tecnológico完了
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Advice Pharma Group srl積極的、募集していない肥満 | 栄養障害 | 体重 | 減量 | 食生活 | 太りすぎと肥満 | 健康行動 | ダイエット、健康 | ダイエット習慣 | ライフスタイル | 栄養、健康 | 行動障害イタリア
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University Hospital, Strasbourg, France積極的、募集していない