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

NCT02406443 | Completed Phase 4 Results

• 1 other identifier: 14-8616
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes, DPP-4 inhibitors, renal sodium excretion

Outcome Measures

Primary Outcomes (1)

• Percent Change in Fractional Excretion of Sodium (FENA)

  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

  3 Hrs post-administration after 1 month and after 1 dose

Secondary Outcomes (6)

• Change in Glomerular Filtration Rate (GFR)

  3 Hrs post-administration after 1 month and after 1 dose

• Change in Fractional Excretion of Lithium (FELi)

  3 Hrs post-administration after 1 month and after 1 dose

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

  3 Hr vs. baseline after 1 dose

• 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

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

  3 Hrs post-administration after 1 month and after 1 dose

Study Arms (2)

Experimental arm

EXPERIMENTAL

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

Drug: Sitaglitpin

Placebo arm

PLACEBO COMPARATOR

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

Other: Placebo

Interventions

Sitaglitpin DRUG

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

Also known as: Januvia

Experimental arm

Placebo OTHER

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

Placebo arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University Health Network - Division of Nephrology

Toronto, Ontario, M5G 2N2, Canada

Location

Related Publications (1)

• 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.

  PMID: 28550195 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Sitagliptin Phosphate

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines

Results Point of Contact

• Title: University Health Network
• Organization: Renal Physiology Laboratory

vesta.lai@uhn.ca

416-340-4800

Study Officials

• Julie Lovshin, MD,PhD

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

  STUDY DIRECTOR

• David I Cherney, MD,PhD

  Division of Nephrology, University Health Network, University of Toronto

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2015
• First Posted: April 2, 2015
• Study Start: March 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: January 1, 2017
• Last Updated: April 5, 2018
• Results First Posted: April 5, 2018

Record last verified: 2018-01

Locations

CA (1)