Impact of c242T Polymorphism of p22phox in Diabetic type1 Nephropathy (NEPHRODIANOX)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Grenoble
ClinicalTrials.gov Identifier:
NCT01371955
First received: June 10, 2011
Last updated: November 14, 2013
Last verified: November 2013
  Purpose

The physiopathology of diabetic nephropathy (DN) is unclear. To investigate risk factor, the investigators choose to look about some oxidative stress genes. Today a one-gene explanation is not really possible. So the theory of some genetic predisposition to DN is more likely.

The aim of the study is to look about the association of the C282T polymorphism of P22phox, a sub unit of the nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) in the occurrence of DN. To follow the oxidative stress pathway of the DN, the investigators also investigate three other polymorphisms: -429 T/C, -374 T/A polymorphism of advanced glycation end-products receptor (AGER) and the p.Arg261Gln polymorphism of the 12 lipoxygenase (ALOX 12). Discordant data suggest a link between the first 2 polymorphisms and DN. The last polymorphism is correlated to albuminuria in diabetic patients.


Condition
Type 1 Diabetes Mellitus
Diabetic Nephropathy

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Impact of c242T Polymorphism of p22phox in the Development of Diabetic Nephropathy,in Caucasian Diabetic Type 1 Patient.

Resource links provided by NLM:


Further study details as provided by University Hospital, Grenoble:

Primary Outcome Measures:
  • comparison of prevalence of homozygous polymorphism between the DN-group and the non-DN group [ Time Frame: on day 1 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • comparison of polymorphism of p22phox between the ND group and the sub-group of non-ND patients with diabetic retinopathy only [ Time Frame: day 1 ] [ Designated as safety issue: No ]
  • comparison of polymorphism prevalence between the 3 groups [ Time Frame: day 1 ] [ Designated as safety issue: No ]
  • delay between diabetes diagnosis and ND onset by genetic polymorphism [ Time Frame: 20 years ] [ Designated as safety issue: No ]
    Kaplan Meier method


Other Outcome Measures:
  • albuminuria [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    mg/day

  • HbA1c [ Time Frame: day 1 ] [ Designated as safety issue: No ]
    HbA1c in %


Biospecimen Retention:   Samples With DNA

We will include 60 patients to reach the required number. We take 2 blood samples: one for genetic analysis and one to determine HBA1c and plasma creatinine. We also take one urinary sample to determine the urinary albumine / creatinine ratio


Enrollment: 162
Study Start Date: January 2011
Study Completion Date: March 2013
Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Groups/Cohorts
diabetic nephropathy group
patient with diabetic nephropathy, defined as Albuminuria > 30 mg/day or urinary Albumine/ creatinine ratio > 3 mg/mmol ; or GFR estimated by MDRD less than 60 ml/min.1,73m². With no other etiology of diabetic nephropathy.
diabetic retinopathy group
patient with diabetic retinopathy defined as showing at least one micro aneurysm on retinography. Without nephropathy defined as above
no complication group
patient without diabetic nephropathy or retinopathy

Detailed Description:

To avoid confounding factors, we choose type 1 diabetic patients. We plan, with the data of literature a number need to be significative with a power of 80% and an Alpha risk at 5%, the inclusion of 160 patients for our primary analyze of p 22 phox. Those patients are included consequentially from the diabetic consultation of the university hospital of Grenoble, if they have a history of more than 20 years of diabetes. Those patients have been separated according to the existence of DN, and their polymorphism. Then we estimate with the Fisher test the prevalence of DN in risky patient, and the prevalence of the risky phenotype in the nephropathic patients. Then we investigate with the same statistical test the -429 T/C,he -374 T/A AGER and p.Arg261Gln 12 ALOX polymorphisms.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

caucasian diabetic type 1 patients with more than 20 years of diabetes duration

Criteria

Inclusion Criteria:

  • caucasian
  • diabetic type 1
  • older than 18 years old
  • written consent

Exclusion Criteria:

  • other etiology of diabetic nephropathy
  • pregnancy
  • other type of diabetes
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01371955

Locations
France
University Hospital of Grenoble
Grenoble, France, 38043
Sponsors and Collaborators
University Hospital, Grenoble
Investigators
Principal Investigator: BENHAMOU pierre yves, MD PhD service de diabétologie
  More Information

No publications provided

Responsible Party: University Hospital, Grenoble
ClinicalTrials.gov Identifier: NCT01371955     History of Changes
Other Study ID Numbers: 1020, 2010-A01074-35
Study First Received: June 10, 2011
Last Updated: November 14, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Grenoble:
diabetic nephropathy
CYBA
p22phox
RAGE
12LOX
genetic
Type 1 Diabetes Mellitus with Diabetic Dermatitis
caucasian
more than twenty years of diabetes duration
older than 18 years
no nephropathy other than diabetic nephropathy

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Kidney Diseases
Diabetic Nephropathies
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Urologic Diseases
Diabetes Complications

ClinicalTrials.gov processed this record on September 18, 2014