The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion (INDORSE)
Effects of DPP-4 Inhibitor Therapy on Renal Sodium Handling and Renal Hemodynamics in Type 2 Diabetes Patients. The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion
Background: Dedicated renal hemodynamic and renal function studies are lacking for DPP-4 inhibitors in patients with Type 2 diabetes; accordingly little is known regarding the mechanisms mediating the renal effects of DPP-4 inhibitors in humans.
Objectives: To evaluate the effect of DPP-4 inhibition acutely (single dose) and following short-term therapy (28 days) on renal sodium handling and renal hemodynamics and function in patients with type 2 diabetes and systolic hypertension.
Design: double-blind, randomized, placebo-controlled trial, Phase IV.
Patient population: 32 patients with Type 2 diabetes, HbA1c (6.5%-9%), with systolic blood pressure ranging from 120-160 mmHg.
Intervention: subjects will be randomized (1:1) to either sitagliptin (100 mg daily) or to placebo (1 tablet daily) for 28 days.
Endpoints: Fractional excretion of sodium, renal function, and renal hemodynamics.
調査の概要
詳細な説明
Background: DPP-4 inhibition improves glycemic control, modestly reduces blood pressure and may also reduce albuminuria in patients with Type 2 diabetes; effects which occur without significantly modifying heart rate or body weight. While preclinical studies have demonstrated that DPP-4 inhibition acutely increases urinary sodium excretion in addition to other favorable renal effects (anti-inflammatory, anti-proteinuric), few studies have examined the renal effects of DPP-4 inhibition either acutely or following short-term therapy in humans with type 2 diabetes. Considering the world-wide prevalence of Type 2 diabetes and the increasing use of DPP-4 inhibitors amongst patients, it is important to ascertain potential non-glycemic effects of DPP-4 inhibitors including those within the kidney.
Study Objectives: To determine effect(s) of DPP-4 inhibition on tubular sodium handling, renal hemodynamics, and renal function.
Study Design: double-blind, randomized, placebo-controlled trial, Phase IV.
Study Patients: 32 patients with Type 2 Diabetes and Systolic Hypertension (SBP 120-160 mmHg).
Endpoints: Fractional excretion of sodium, renal function (measured GFR), renal hemodynamics (effective renal plasma flow, filtration fraction, renal blood flow, renal vascular resistance), systemic hemodynamics (non-invasive cardiac monitoring), plasma neurohormones, urinary vasoactive mediators, markers of free radical stress.
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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Ontario
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Toronto、Ontario、カナダ、M5G 2N2
- University Health Network - Division of Nephrology
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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:
- Individuals of 18-70 years of age,
- with Type 2 Diabetes,
- with an HbA1c (6.5%-9%),
- and with a systolic blood pressure (120-160 mmHg).
Exclusion Criteria:
Individuals with:
- Type 1 Diabetes,
- eGFR <50mL/min/1.73m,
- pregnancy or breast feeding,
- significant cardiac, pulmonary or liver disease,
- prior history of pancreatitis, medullary thyroid cancer, multiple endocrine neoplasia syndromes,
- SBP >161 mmHg, 7) DBP >100 mmHg,
- alcohol or substance abuse,
- states of secondary hypertension.
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：他の
- 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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実験的：Experimental arm
sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days
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Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days
他の名前：
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プラセボコンパレーター：Placebo arm
placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days
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Oral tablet (no medicinal ingredients) administered once daily for 28 days
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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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Percent Change in Fractional Excretion of Sodium (FENA)
時間枠：3 Hrs post-administration after 1 month and after 1 dose
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FENA at 3Hrs post-study drug administration after 1 month compared to FENA at 3Hrs post-study drug administration after 1 dose expressed as percent change, sitagliptin vs. placebo
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3 Hrs post-administration after 1 month and after 1 dose
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Glomerular Filtration Rate (GFR)
時間枠：3 Hrs post-administration after 1 month and after 1 dose
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Measured GFR (Inulin Clearance) at 3Hrs post study-drug after 1 month compared to Measured GFR at 3Hrs post-study drug after 1 dose, sitagliptin vs. placebo
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3 Hrs post-administration after 1 month and after 1 dose
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Change in Fractional Excretion of Lithium (FELi)
時間枠：3 Hrs post-administration after 1 month and after 1 dose
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FELi at 3 Hr post-study drug administration after 1 month compared to FELI at 3hrs post-study drug administration after 1 dose, sitagliptin vs. placebo
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3 Hrs post-administration after 1 month and after 1 dose
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Change From Baseline in SDF-1alpha^1-67 (Intact) Measured by Immunoaffinity and Tandem Mass Spectrometry
時間枠：3 Hr vs. baseline after 1 dose
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Plasma concentration of SDF-1alpha^1-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
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3 Hr vs. baseline after 1 dose
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Change From Baseline in SDF-1alpha^3-67 (Truncated) Measured by Tandem Mass Spectrometry With Antibody-based Affinity Enrichment
時間枠：3Hrs vs baseline after 1 dose
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Plasma concentration of SDF-1alpha^3-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
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3Hrs vs baseline after 1 dose
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Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring
時間枠：3 Hrs post-administration after 1 month and after 1 dose
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SBP by Non-Invasive cardiac output monitoring at 3Hrs post- study drug administration after 1 month compared to SBP by Non-invasive cardiac output monitoring at 3Hrs after 1 dose, sitagliptin vs placebo
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3 Hrs post-administration after 1 month and after 1 dose
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Change in Effective Renal Plasma Flow (ERPF)
時間枠：3 Hrs post-administration after 1 month and after 1 dose
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ERPF (para-aminohippurate clearance) 3Hrs post-study drug administration after 1 month compared to ERPF at 3Hhrs post-study drug administration after 1 dose, sitagliptin vs placebo
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3 Hrs post-administration after 1 month and after 1 dose
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協力者と研究者
捜査官
- スタディディレクター：Julie Lovshin, MD,PhD、Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of Toronto
- 主任研究者：David I Cherney, MD,PhD、Division of Nephrology, University Health Network, University of Toronto
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
一次修了 (実際)
研究の完了 (実際)
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 (実際)
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
本研究に関する用語
追加の関連 MeSH 用語
その他の研究ID番号
- 14-8616
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