Type 2 DiabetesPhase 4INDORSENCT02406443
The INDORSE Study: Inhibition of Dipeptidyl Peptidase IV: Outcomes on Renal Sodium Excretion
A Phase 4 study testing Sitaglitpin in people with Type 2 Diabetes, run by University Health Network, Toronto at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Sitaglitpin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 36 participants
- Where
- 1 siteCanada
- Study dates
- Mar 2015to Jan 2017
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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,
Show all 9Show fewer
- SBP >161 mmHg, 7) DBP >100 mmHg,
- alcohol or substance abuse,
- states of secondary hypertension.
Trial locations and contacts
1 site in 1 country.
Canada1 site
University Health Network - Division of Nephrology
Toronto, Ontario, M5G 2N2
About this study
Official 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
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.
Read more
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.
Read the 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
- Being tested
- Sitaglitpin, Placebo
- Keywords
- Type 2 Diabetes, DPP-4 inhibitors, renal sodium excretion
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitaglitpinDrug
Also called Januvia
Oral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days
PlaceboOther
Oral tablet (no medicinal ingredients) administered once daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | sitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days Receives: Drug: Sitaglitpin |
| Placebo arm | Placebo comparator | placebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 3 Hrs post-administration after 1 month and after 1 dose
Secondary outcomes (6)
Change in Glomerular Filtration Rate (GFR)
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
Measured: 3 Hrs post-administration after 1 month and after 1 dose
Change in Fractional Excretion of Lithium (FELi)
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
Measured: 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
Plasma concentration of SDF-1alpha^1-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
Measured: 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
Plasma concentration of SDF-1alpha^3-67 (intact) measured by quantitative mass spectrometry methods after antibody-based affinity enrichment, sitagliptin vs. placebo
Measured: 3Hrs vs baseline after 1 dose
Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring
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
Measured: 3 Hrs post-administration after 1 month and after 1 dose
Change in Effective Renal Plasma Flow (ERPF)
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
Measured: 3 Hrs post-administration after 1 month and after 1 dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2015 (estimated)
- Study startMar 2015
- Primary completionJun 2016
- Study completionJan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Julie Lovshin, MD,PhD, Study director, Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of TorontoDavid I Cherney, MD,PhD, Principal investigator, Division of Nephrology, University Health Network, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02406443
- Sponsor's protocol ID
- 14-8616
- Acronym
- INDORSE
- Status last verified
- Jan 2018
- First submitted
- 30 Mar 2015
- Last updated
- 5 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 28550195
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02406443
- Acronym / sponsor ID
- INDORSE / 14-8616
- Conditions
- Type 2 Diabetes
- Keywords
- Type 2 Diabetes, DPP-4 inhibitors, renal sodium excretion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2015
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 2 Apr 2015 (estimated)
- Results
- Posted 5 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Drug: Sitaglitpinsitagliptin (DPP-4 inhibitor) oral tablet (100 mg); Januvia; administered once daily for 28 days |
| Placebo arm | Placebo comparator | Other: Placeboplacebo (no medicinal ingredients) oral tablet (100 mg); administered once daily for 28 days |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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).
Key exclusion criteria (9 listed)
- Individuals with:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SitaglitpinAlso: JanuviaOral DPP-4 inhibitor, 100 mg tablet administered once daily for 28 days | Drug | Experimental arm |
| PlaceboOral tablet (no medicinal ingredients) administered once daily for 28 days | Other | Placebo arm |
Primary outcome
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
6 secondary outcomes
Change in Glomerular Filtration Rate (GFR)
Time frame: 3 Hrs post-administration after 1 month and after 1 dose
Change in Fractional Excretion of Lithium (FELi)
Time frame: 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
Time frame: 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
Time frame: 3Hrs vs baseline after 1 dose
Change in Systolic Blood Pressure (SBP), Non-invasive Cardiac Output Monitoring
Time frame: 3 Hrs post-administration after 1 month and after 1 dose
Change in Effective Renal Plasma Flow (ERPF)
Time frame: 3 Hrs post-administration after 1 month and after 1 dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28550195Lovshin 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Lovshin, MD,PhD study director
Lunenfeld Tanenbaum Reserach Institute, Divsion of Endocrinology and Metabolism, University of Toronto
David I Cherney, MD,PhD principal investigator
Division of Nephrology, University Health Network, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Sitaglitpin in people with Type 2 Diabetes, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Fractional Excretion of Sodium (FENA) (time frame: 3 Hrs post-administration after 1 month and after 1 dose). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02406443, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2018.