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.
연구 개요
상세 설명
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.
연구 유형
등록 (실제)
단계
- 4단계
연락처 및 위치
연구 장소
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Ontario
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Toronto, Ontario, 캐나다, M5G 2N2
- University Health Network - Division of Nephrology
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 다른
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 삼루타
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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
다른 이름들:
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위약 비교기: 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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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percent Change in Fractional Excretion of Sodium (FENA)
기간: 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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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Change in Glomerular Filtration Rate (GFR)
기간: 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)
기간: 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
기간: 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
기간: 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
기간: 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)
기간: 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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공동 작업자 및 조사자
수사관
- 연구 책임자: Julie Lovshin, MD,PhD, Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of Toronto
- 수석 연구원: David I Cherney, MD,PhD, Division of Nephrology, University Health Network, University of Toronto
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- 14-8616
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