Effects of DPP4 Inhibitor on Cisplatin Induced Acute Kidney Injury

NCT02250872 — Phase 2 / Phase 3, Unknown, 182 participants, Seoul National University Bundang Hospital

ClinicalTrials Daily · Areas · Conditions · Drugs · Sponsors ·

Effect of DPP4 Inhibitors on Cisplatin-induced Acute Kidney Injury

Registry	NCT02250872
Status	Unknown
Phase	Phase 2 / Phase 3
Study type	Interventional; randomized, parallel, masking: double, treatment
Enrollment	182 (Estimated)
Sponsor	Seoul National University Bundang Hospital (Other); collaborators: LG Life Sciences
Conditions	Cancer, Cisplatin Adverse Reaction
Interventions	Gemigliptin, Placebo, Cisplatin (Drug)
Dates	start 2014-12-01, primary completion 2018-02-01 (estimated), completion 2018-06-01 (estimated), first posted 2014-09-26, last updated 2016-04-20
Locations	1 site in South Korea

-Summary

Cisplatin is a potent chemotherapeutic agent, however, its nephrotoxicity manifested by acute kidney injury (AKI) often limits applicability. Dipeptidylpeptidase-4 (DPP4) inhibitors are well known to improve glucose intolerance by augmentation of endogenous glucagon like peptide (GLP-1) and glucose-dependent insulinotropic peptide (GIP). DPP4 inhibitor also has the potential anti-apoptotic and renoprotective effect in a mouse model of cisplatin-induced AKI. This is a single-center, randomized, double-blind, parallel-group, placebo-controlled, prospective study to investigate the renoprotective effect of DPP4 inhibitor on cisplatin-induced AKI. A total 182 patients, who are scheduled to treat with cisplatin, will be recruited and randomly assigned to either Gemigliptin or placebo groups. Subjects will take study drugs for 8 days starting from one day before cisplatin treatment. Serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) will be measured at 7 days after cisplatin treatment.

Expand all sections · Collapse all

+Detailed description

This study will investigate possible renoprotective effects of DPP4 inhibitor on cisplatin induced acute kidney injury.

+Arms and interventions

Arm	Type	Interventions	Description
Experimental: Gemigliptin and Cisplatin	Active comparator	Drug: Gemigliptin; Drug: Cisplatin	Gemigliptin 100mg daily in two divided doses for 8 days starting from one day before cisplatin-treatment
Control arm	Placebo comparator	Drug: Placebo; Drug: Cisplatin	Placebo 100mg daily in two divided doses for 8 days starting from one day before cisplatin-treatment

Gemigliptin (Drug), also known as Zemiglo: Gemigliptin 100mg in 2 divided doses plus cisplatin
Placebo (Drug), also known as Identical inert tablet to mimic gemigliptin (50mg): 100mg in 2 divided doses plus cisplatin
Cisplatin (Drug): All patients will receive intravenous cisplatin

+Outcome measures

Primary outcomes

Incidence of acute kidney injury defined as any of the followings [up to 7 days]: * Increase in sCr by ≥ 0.3 mg/dl * Increase in sCr to ≥ 1.5 times baseline * Decrease in eGFR to ≥ 25% All subjects receive Gemigliptin or placebo at a total dose of 100mg (50mg twice a day) for 8 consecutive days, serum creatinine will be measured.

Secondary outcomes

delta Cr [Time Frame: up to 7 days]: Change of serum creatinine from baseline to 7 days after cisplatin treatment.
delta eGFR [up to 7 days]: Change of glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration equations (CKD EPI) from baseline to 7 days after cisplatin treatment.

+Eligibility

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* age > 18 years
* cancer patients treated with intravenous cisplatin
* written consent

Exclusion Criteria:

* Diabetes mellitus
* Chronic kidney disease stage IV-V (eGFR < 30ml/min/1.73m2)
* History of transplantation
* History of acute kidney injury before randomization
* Use of other nephrotoxic agents such as non steroidal anti-inflammatory drugs, aminoglycosides, colistin, vancomycin
* Receiving contrast media during last 72 hours
* Liver disease (bilirubin > 2 mg/dl, transaminase levels >2.5 times the upper limit normal)
* Active infection
* Patients with high risks of dehydration owing to poor oral intake
* High blood pressure (> 180/110 mmHg despite antihypertensive medications)
* Hypersensitivity to Gemigliptin or its excipients
* Low compliance to Gemigliptin treatment

+Locations (1)

Facility	City	Country	Status
Seoul National University Bundang Hospital	Seongnam-si, Gyeonggi-do	South Korea	Recruiting

+Publications

Results publication: Katagiri D, Hamasaki Y, Doi K, Okamoto K, Negishi K, Nangaku M, Noiri E. Protection of glucagon-like peptide-1 in cisplatin-induced renal injury elucidates gut-kidney connection. J Am Soc Nephrol. 2013 Dec;24(12):2034-43. doi: 10.1681/ASN.2013020134. Epub 2013 Oct 3. PMID 24092928
Results publication: Baek SH, Kim SH, Kim JW, Kim YJ, Lee KW, Na KY. Effects of a DPP4 inhibitor on cisplatin-induced acute kidney injury: study protocol for a randomized controlled trial. Trials. 2015 May 29;16:239. doi: 10.1186/s13063-015-0772-4. PMID 26021829

+Investigators

Ki Young Na, Principal investigator, Seoul National University Bundang Hospital