Clinical trial NCT04521049: Tubular Markers in Response to Saxagliptin Therapy
Official title: A New Clinical Utility for Tubular Markers to Identify Kidney Responders to Saxagliptin Treatment in Patients With Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: saxagliptin
uNGAL
u L-FABP
DKD
Lead sponsor: Beni-Suef University
Sponsor class: OTHER
First posted: 2020-08-20
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: the study aims to investigate whether treatment with saxagliptin would induce beneficial changes in renal NGAL and L-FABP biomarkers and if they would be used as a tool to identify patients' categories with a particular renal response to DPP-4inhibition. Secondly, to find an association between NGAL and L-FABP, and the relevant renal parameters for both baseline values and rate of changes across defined time points.

Detailed description: Diabetic kidney disease (DKD) is considered a substantial cause of end-stage kidney disease (ESKD) worldwide. Incorporation of renoprotective options during interventions to prevent the development of DKD and attenuation of its progression; is of the utmost importance. Incretin-based therapies, specifically dipeptidyl peptidase 4 (DPP-4) inhibitors exhibited albuminuria lowering potential beyond their antihyperglycemic effects. Saxagliptin, a potent selective DPP-4 inhibitor which has been used as monotherapy or in combination with antidiabetics, has demonstrated great renal efficiency on both experimental and clinical scale .

Although albumin excretion rate (AER) is a powerful predictor of kidney function deterioration and progressive renal dysfunction, it is primarily a marker of glomerular damage and it has some drawbacks. For example; some patients may follow a non-albuminuric pathway to kidney impairment, others do not progress to macroalbuminuria but remain at microalbuminuria or even regress to normoalbuminuria. Thus, more sensitive and specific renal biomarkers than AER will be valuable in predicting early kidney injury and the progression of diabetic renal damage.

Besides glomerular damage, tubulointerstitial dysfunction largely contributes to the pathology of diabetic nephropathy. Neutrophil gelatinase-associated lipocalin (NGAL) and liver type fatty acid binding protein (L-FABP) are apparent as excellent biomarkers of tubular damage and are earlier predictors of acute kidney injury relative to microalbuminuria. NGAL is produced by neutrophils, highly expressed in tubular epithelium and released from tubular cells following damage . L-FABP is expressed in the proximal tubules and secreted into urine upon tubulointerstitial damage. Clinical significance of these biomarkers lies in their emergence in normoalbuminuric patients and their association with increased albuminuria and progression to ESRD with sustained high urinary markers' levels.

Eligibility criteria: Inclusion Criteria:

* T2 DM,
* prevalent albuminuria (30-3000mg/g),
* controlled hypertension (defined as blood pressure \<140/90 mm Hg) on a selected angiotensin receptor blocker, olmesartan 20mg/day for at least 4 weeks before intervention.

Exclusion Criteria:

* type 1 diabetes,
* poorly controlled hypertension (140-160/90-100 mm Hg),
* pancreatitis,
* malignancies
* albuminuria more than 3000mg/g.
* cardiovascular diseases (acute myocardial infarction, cerebrovascular disease in the past 6months,
* End Stage Renal Disease (ESRD) on chronic dialysis, renal transplant, a serum creatinine \>6.0 mg/dL, or estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2.

Primary outcomes:
measure: to measure renal effect of saxagliptin on tubular markers
timeFrame: 3 months
measure: to measure effect of saxagliptin on renal on albuminuria
timeFrame: 3 months
measure: to classify renal responders to saxagliptin using tubular markers
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Al Qāhirah Al Jadīdah
country: Egypt
facility: Faculty of Pharmacy
Study officials:
affiliation: Clinical Pharmacology Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
name: Ahmed A Elberry, prof
role: STUDY_CHAIR
References: