Clinical trial NCT01371955: Impact of c242T Polymorphism of p22phox in Diabetic type1 Nephropathy
Official title: Impact of c242T Polymorphism of p22phox in the Development of Diabetic Nephropathy,in Caucasian Diabetic Type 1 Patient.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes Mellitus
Diabetic Nephropathy
Keywords: 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
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
First posted: 2011-06-13
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: caucasian diabetic type 1 patients with more than 20 years of diabetes duration

Brief summary: 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.

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 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

Primary outcomes:
measure: comparison of prevalence of homozygous polymorphism between the DN-group and the non-DN group
timeFrame: on day 1
Secondary outcomes:
measure: comparison of polymorphism of p22phox between the ND group and the sub-group of non-ND patients with diabetic retinopathy only
timeFrame: day 1
measure: comparison of polymorphism prevalence between the 3 groups
timeFrame: day 1
measure: delay between diabetes diagnosis and ND onset by genetic polymorphism
timeFrame: 20 years
Other outcomes:
measure: albuminuria
timeFrame: day 1
measure: HbA1c
timeFrame: day 1
Locations:
city: Grenoble
country: France
facility: University Hospital of Grenoble
Study officials:
affiliation: service de diabétologie
name: BENHAMOU pierre yves, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: