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NCT Number: NCT02406443

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.

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Key information

Conditions

Type 2 Diabetes Diabetes Mellitus Diabetes Mellitus, Type 2 Endocrine System Diseases Glucose Metabolism Disorders Metabolic Diseases Nutritional and Metabolic Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

University Health Network - Division of Nephrology

Toronto, Ontario, M5G 2N2, Canada

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Sitaglitpin

Drug

Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days

Other names: Januvia

Placebo

Other

Oral tablet (no medicinal ingredients) administered once daily for 28 days

Primary outcomes

  1. Percent Change in Fractional Excretion of Sodium (FENA)

    Time frame: 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 outcomes

  1. Change in Glomerular Filtration Rate (GFR)

    Time frame: 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

  2. Change in Fractional Excretion of Lithium (FELi)

    Time frame: 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

  3. Change From Baseline in SDF-1alpha^1-67 (Intact) Measured by Immunoaffinity and Tandem Mass Spectrometry

    Time frame: 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

  4. Change From Baseline in SDF-1alpha^3-67 (Truncated) Measured by Tandem Mass Spectrometry With Antibody-based Affinity Enrichment

    Time frame: 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

  5. Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring

    Time frame: 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

  6. Change in Effective Renal Plasma Flow (ERPF)

    Time frame: 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

Sponsors and collaborators

Lead sponsor

University Health Network, Toronto

Other

Collaborators

  • Merck Sharp & Dohme LLC

Registry information

Official study title

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

Acronym: INDORSE

Important dates

Study start
2015
Primary completion
2016
Study completion
2017
First posted
Apr 2, 2015
Registry last updated
Apr 5, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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