Maximal Dose of Angiotensin Converting Enzyme (ACE) Inhibitor for Treatment of Diabetic Kidney Disease
Optimal Dose of ACE Inhibitor for Treatment of Diabetic Nephropathy in Type 1 Diabetic Patients With Hypertension and Diabetic Nephropathy
The primary aim is to evaluate the anti proteinuric effect of increasing doses of the ACE inhibitor, lisinopril: 20, 40 and 60 mg daily in type 1 diabetic patients with hypertension and diabetic nephropathy.
The secondary aim is to evaluate the effect on blood pressure (24 hour ambulatory blood pressure) and kidney function (glomerular filtration rate (GFR)).
The tertiary aim is to evaluate differences in response to treatment according to ACE/insertion/deletion (ID)-genotypes and other genetic variants in the genes of the renin angiotensin system.
調査の概要
詳細な説明
This is a randomized, double-blind cross-over study with three treatment periods consisting of 20, 40 and 60 mg lisinopril daily in random order. The endpoints of the study will be examined after each treatment period. There is no wash out between treatment periods. To minimize the risk of hypotension every treatment period starts with 20 mg lisinopril for two weeks. Thus, the risk of adverse effects is minimized and an increase in dose from 0 mg to 60 mg lisinopril is avoided.
The patients usual antihypertensive treatments will be stopped in a period of 8 weeks (wash out) before randomization. Since diuretic drugs will be needed by almost every patient in the study to avoid oedema all patients will be treated with lasix retard 60 - 120 mg daily.
Patients:
60 type 1 diabetic patients with diabetic nephropathy and hypertension (blood pressure > 135 mm Hg systolic and/or 85 mm Hg diastolic).
Methods:
The endpoints of the study will be examined at baseline and after each treatment period corresponding to 8, 16, and 24 weeks after randomization. The following parameters are determined after each treatment period: Albuminuria (determined from three consecutive 24 hours urine collections), kidney function (GFR - by plasma clearance of 51Cr-EDTA ), and 24 hour ambulatory blood pressure (TM-2420/2421). Furthermore, the concentrations of TGF-ß, sodium, creatinine, and carbamide in the 24 hour urinary samples are determined. The plasma concentration of albumin, renin, angiotensin II, and aldosterone is measured.
DNA is extracted from a blood sample and genetic variants in the renin-angiotensin system are measured including the ACE/ID genotype.
Endpoints:
Primary endpoint: albuminuria ; Secondary endpoints: blood pressure (24 hour ambulatory) and GFR; Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.
研究の種類
入学
段階
- 適用できない
連絡先と場所
研究場所
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-
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Gentofte、デンマーク、2820
- Steno Diabetes center
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Type 1 diabetes (WHO criteria)
- Diabetic nephropathy (2 out of 3 consecutive 24 hour urinary samples with albumin excretion > 300 mg/24hour and diabetic retinopathy in the absence of signs of other kidney or urinary tract disease) 27 or diabetic glomerulosclerosis verified by biopsy.
- Hypertension: Blood pressure > 135 mmHg systolic and/or 85 mm Hg diastolic repeatedly.
- Age from 18 to 70 years.
Exclusion Criteria:
- Age < 18 years or > 70 years.
- Pregnancy or fertile women not using adequate anticonceptive (intrauterine device, sterilization, or oral anticonceptive)
- Malignant hypertension.
- Blood pressure > 180/105 mm Hg
- Known renal artery stenosis
- GFR < 30 ml/min/1.73 m²
- Serum potassium > 4.8 mmol/ l
- Heart failure, myocardial infarction, unstable angina or coronary bypass operation within the previous three months.
- Abuse of drugs or alcohol.
- Not able to understand the written information.
- Known intolerance to ACE inhibitors.
- Chronic use of non steroid inflammatory drugs or aspirin (above 1 g/day)
研究計画
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:防止
- 割り当て:ランダム化
- 介入モデル:クロスオーバー割り当て
- マスキング:ダブル
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 |
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albuminuria
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二次結果の測定
結果測定 |
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blood pressure (24 hour ambulatory) and GFR.
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Tertiary: differences in response to treatment in patients with different ACE/ID and other renin angiotensin system genotypes.
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協力者と研究者
捜査官
- スタディチェア:Hans-Henrik Parving, MD、Steno Diabetes Center Copenhagen
出版物と役立つリンク
研究記録日
主要日程の研究
研究開始
研究の完了
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
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。