The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion
- Conditions
- Type 2 Diabetes
- Interventions
- Drug: SitaglitpinOther: Placebo
- Registration Number
- NCT02406443
- Lead Sponsor
- University Health Network, Toronto
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- 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).
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Experimental arm Sitaglitpin sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Placebo arm Placebo placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days
- Primary Outcome Measures
Name Time Method Percent Change in Fractional Excretion of Sodium (FENA) 3 Hrs post-administration after 1 month and after 1 dose 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
- Secondary Outcome Measures
Name Time Method Change in Glomerular Filtration Rate (GFR) 3 Hrs post-administration after 1 month and after 1 dose 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
Change in Fractional Excretion of Lithium (FELi) 3 Hrs post-administration after 1 month and after 1 dose 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
Change From Baseline in SDF-1alpha^1-67 (Intact) Measured by Immunoaffinity and Tandem Mass Spectrometry 3 Hr vs. baseline after 1 dose Plasma concentration of SDF-1alpha\^1-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
Change From Baseline in SDF-1alpha^3-67 (Truncated) Measured by Tandem Mass Spectrometry With Antibody-based Affinity Enrichment 3Hrs vs baseline after 1 dose Plasma concentration of SDF-1alpha\^3-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring 3 Hrs post-administration after 1 month and after 1 dose 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
Change in Effective Renal Plasma Flow (ERPF) 3 Hrs post-administration after 1 month and after 1 dose 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
Trial Locations
- Locations (1)
University Health Network - Division of Nephrology
🇨🇦Toronto, Ontario, Canada