- ICH GCP
- US Clinical Trials Registry
- Klinisk forsøg NCT02406443
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.
Studieoversigt
Status
Betingelser
Intervention / Behandling
Detaljeret beskrivelse
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.
Undersøgelsestype
Tilmelding (Faktiske)
Fase
- Fase 4
Kontakter og lokationer
Studiesteder
-
-
Ontario
-
Toronto, Ontario, Canada, M5G 2N2
- University Health Network - Division of Nephrology
-
-
Deltagelseskriterier
Berettigelseskriterier
Aldre berettiget til at studere
Tager imod sunde frivillige
Køn, der er berettiget til at studere
Beskrivelse
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.
Studieplan
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Andet
- Tildeling: Randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Tredobbelt
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
---|---|
Eksperimentel: Experimental arm
sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days
|
Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days
Andre navne:
|
Placebo komparator: Placebo arm
placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days
|
Oral tablet (no medicinal ingredients) administered once daily for 28 days
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Percent Change in Fractional Excretion of Sodium (FENA)
Tidsramme: 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
|
3 Hrs post-administration after 1 month and after 1 dose
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
---|---|---|
Change in Glomerular Filtration Rate (GFR)
Tidsramme: 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
|
3 Hrs post-administration after 1 month and after 1 dose
|
Change in Fractional Excretion of Lithium (FELi)
Tidsramme: 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 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
Tidsramme: 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
|
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
Tidsramme: 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
|
3Hrs vs baseline after 1 dose
|
Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring
Tidsramme: 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
|
3 Hrs post-administration after 1 month and after 1 dose
|
Change in Effective Renal Plasma Flow (ERPF)
Tidsramme: 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
|
3 Hrs post-administration after 1 month and after 1 dose
|
Samarbejdspartnere og efterforskere
Samarbejdspartnere
Efterforskere
- Studieleder: Julie Lovshin, MD,PhD, Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of Toronto
- Ledende efterforsker: David I Cherney, MD,PhD, Division of Nephrology, University Health Network, University of Toronto
Publikationer og nyttige links
Datoer for undersøgelser
Studer store datoer
Studiestart
Primær færdiggørelse (Faktiske)
Studieafslutning (Faktiske)
Datoer for studieregistrering
Først indsendt
Først indsendt, der opfyldte QC-kriterier
Først opslået (Skøn)
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
Sidst verificeret
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
- Glukosemetabolismeforstyrrelser
- Metaboliske sygdomme
- Sygdomme i det endokrine system
- Diabetes mellitus
- Diabetes mellitus, type 2
- Hypoglykæmiske midler
- Lægemidlers fysiologiske virkninger
- Molekylære mekanismer for farmakologisk virkning
- Enzymhæmmere
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Proteasehæmmere
- Inkretiner
- Dipeptidyl-Peptidase IV-hæmmere
- Sitagliptin fosfat
Andre undersøgelses-id-numre
- 14-8616
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