Clinical trial NCT02343094: Phenylbutyrate in Proteinuric Nephropathies
Official title: Phenylbutyrate Effect on Lcn2 Urianry Expression in Proteinuric Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Proteinuric Diseases
Keywords: Proteinuria
Lipocalin 2
Neutrophil gelatinase associated lipocalin
ELISA
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-01-21
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether sodium phenylbutyrate can reduce Lcn2 urinary expression in proteinuric patients.

Detailed description: Proteinuria is a major prognosis factor of chronic kidney disease (CKD) progression. Convergent evidences from clinical and experimental studies indicate that albuminuria and proteinuria are not simply a marker of CKD progression, but an active player in the evolution of the disease. Mechanistically, it has been shown that proteinuria induces endoplasmic reticulum stress in tubular cells, leading to induction of lipocalin 2/NGAL, a critical element of CKD progression. Moreover, proteinuric mice treated with phenylbutyrate are protected from CKD progression.

The aim of this study is to evaluate the efficacy of phenybutyrate, a molecular chaperone which inhibits ER stress, on the proteinuria-induced NGAL expression. Urinary NGAL/creatinine ratio will be evaluated in proteinuric patients before and under treatment with phenylbutyrate.

Eligibility criteria: Inclusion Criteria:

* Chronic Kidney disease for ore than 3 months
* Proteinuria \> 1g/d or 0,1g/mmmol creatinine
* eGFR \>30ml/mn/1,73m2
* written informed consent
* affiliated with social security health insurance

Exclusion Criteria:

* Women with childbearing potential
* Recent (\<3 months) modification of ACE inhibitors or ARB
* Acute renal failure
* eGFR \<30ml/mn/1,73m2
* Nephrotic syndrome (albuminélia \<30g/l)
* Infection with HIV, HCV, HBV
* Liver insufficiency
* No affiliated with social security health insurance
* inclusion in another protocol of biomedical research
* risk of non-adherence to protocol and visits
* patients having a cardiac insufficiency of grade 3 or 4
* patient requiring of a strict salt-free diet
* patients under corticoids or immunosuppresseurs
* clinical intolerance in the treatment
* intolerance in the fructose, the syndrome of malabsorption glucose and galactose or a deficit in sucrase / isomaltase
* patients treated by Probenecide

Primary outcomes:
measure: Urinary Lcn2/creatinine ratio
timeFrame: Day 7, Day 15, Day 21, Day 28
Secondary outcomes:
measure: Urinary protein/creatinine ratio
timeFrame: Day 7
measure: Urinary protein/creatinine ratio
timeFrame: Day 15
measure: Urinary protein/creatinine ratio
timeFrame: Day 21
measure: Urinary protein/creatinine ratio
timeFrame: Day 28
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
Study officials:
affiliation: Service de Néphrologie Adulte, Hôpital Necker
name: Bertrand KNEBELMANN
role: PRINCIPAL_INVESTIGATOR
References: