The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion

NCT ID: NCT02406443

Last Updated: 2018-04-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2017-01-31

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.

Conditions

Type 2 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Experimental arm

sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days

Group Type: EXPERIMENTAL

Sitaglitpin

Intervention Type: DRUG

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

Placebo arm

placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

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

Interventions

Sitaglitpin

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

Intervention Type: DRUG

Placebo

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

Intervention Type: OTHER

Other Intervention Names

Januvia

Eligibility Criteria

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:

1. Type 1 Diabetes,

2. eGFR <50mL/min/1.73m,

3. pregnancy or breast feeding,

4. significant cardiac, pulmonary or liver disease,

5. prior history of pancreatitis, medullary thyroid cancer, multiple endocrine neoplasia syndromes,

6. SBP >161 mmHg, 7) DBP >100 mmHg,

7. alcohol or substance abuse,

8. states of secondary hypertension.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Julie Lovshin, MD,PhD

Role: STUDY_DIRECTOR

Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of Toronto

David I Cherney, MD,PhD

Role: PRINCIPAL_INVESTIGATOR

Division of Nephrology, University Health Network, University of Toronto

Locations

University Health Network - Division of Nephrology

Toronto, Ontario, Canada

Countries

Canada

References

Lovshin JA, Rajasekeran H, Lytvyn Y, Lovblom LE, Khan S, Alemu R, Locke A, Lai V, He H, Hittle L, Wang W, Drucker DJ, Cherney DZI. Dipeptidyl Peptidase 4 Inhibition Stimulates Distal Tubular Natriuresis and Increases in Circulating SDF-1alpha1-67 in Patients With Type 2 Diabetes. Diabetes Care. 2017 Aug;40(8):1073-1081. doi: 10.2337/dc17-0061. Epub 2017 May 26.

Reference Type: DERIVED

PMID: 28550195 (View on PubMed)

Other Identifiers

14-8616

Identifier Type: -

Identifier Source: org_study_id