Clinical trial NCT02431234: Arterial Calcification in the Diabetes
Official title: Study of the Mechanisms of the Arterial Calcification of the Members Subordinates in the Diabetes (Implication of the System RANK / RANKL / OSTEOPROTEGERINE)
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Diabetic Vascular Diseases
Arteriosclerosis Obliterans
Monckeberg Medial Calcific Sclerosis
Keywords: Type 2 diabetes
Arterial calcification
Mediacalcosis
Calcium score
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2015-04-30
Enrollment: 169
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Men and women with type 2 diabetes and known coronary artery disease

Brief summary: The blood concentration of the protein RANKL could be predictive of the calcification of the leg arteries, which is a major complication occurring during diabetes. The objective of the DIACART study is to show that blood RANKL concentration predict the progression of calcification of the leg arteries in diabetic patients, independently of other cardiovascular risk factors.

Detailed description: Introduction: Peripheral arterial disease (PAD) is the primary major amputation risk factor in diabetes. The PAD is particularly common among diabetic patients at high cardiovascular risk (20-30% of coronary patients have PAD). The calcification of atherosclerotic plaque and media leg arteries contributes to narrowing of the arterial lumen and exposes the diabetic patient to critical limb ischemia. The receptor RANK (Receptor Activator for Nuclear Factor κ B) and its ligand RANKL form a complex which initially was described as being involved in bone metabolism by activating osteoclasts but the RANK / RANKLigand system could also be involved in the process calcification and arterial obstruction, especially in the lower limbs. Currently there is anti-RANKL antibody used in humans that could possibly slow down this process. But it is necessary to prove the involvement of this system in PAD in diabetic patients at high cardiovascular risk before proposing a therapeutic trial.

Assumptions: the concentration of RANKL could be predictive of calcification of leg arteries in diabetes Main objective: To show that serum RANKL concentrations predict the progression of calcification of the leg arteries in diabetic patients, independently of other cardiovascular risk factors.

Secondary Objectives:

* To show the link between other proteins of bone remodeling, markers of inflammation and glycation, and calcification of leg arteries.
* Measuring the rate of calcification leg arteries.
* Phenotype diabetic patients who have the highest rate of calcification. Primary Outcome: Predictive power of serum RANKL concentration at T0 on the progression of calcification of leg arteries between T0 and T24 months.

Methodology: prospective observational study. The calcium score of leg arteries will be evaluated by a scanner at T0 and 24 months.

Inclusion criteria:

* type 2 diabetes
* women over 60
* men over 50 years
* men and women with known coronary artery disease Non-inclusion criteria:
* severe renal failure
* immunodeficiency
* acute infectious or inflammatory disease
* history of bypass surgery or sub-popliteal angioplasty Number of subjects required: 188 patients will be included. Total study duration: 24 months Inclusion period: 24 months

Eligibility criteria: Inclusion criteria:

* type 2 diabetes
* women over 60
* men over 50 years
* men and women with known coronary artery disease

Non-Exclusion criteria:

* severe renal failure
* immunodeficiency
* acute infectious or inflammatory disease
* history of bypass surgery or sub-popliteal angioplasty

Primary outcomes:
measure: Serum RANKL concentrations
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: Paris
country: France
facility: Groupe Hospitalier Pitié Salpetrière
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Olivier Bourron, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Carlier A, Phan F, Szpigel A, Hajduch E, Salem JE, Gautheron J, Le Goff W, Guerin M, Lachkar F, Ratziu V, Hartemann A, Ferre P, Foufelle F, Bourron O. Dihydroceramides in Triglyceride-Enriched VLDL Are Associated with Nonalcoholic Fatty Liver Disease Severity in Type 2 Diabetes. Cell Rep Med. 2020 Dec 22;1(9):100154. doi: 10.1016/j.xcrm.2020.100154. eCollection 2020 Dec 22.
citation: Bourron O, Phan F, Diallo MH, Hajage D, Aubert CE, Carlier A, Salem JE, Funck-Brentano C, Kemel S, Cluzel P, Redheuil A, Davaine JM, Massy Z, Mentaverri R, Bonnefont-Rousselot D, Gillery P, Jaisson S, Vermeer C, Lacorte JM, Bouziri N, Laroche S, Amouyal C, Hartemann A. Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study. Cardiovasc Diabetol. 2020 Sep 18;19(1):140. doi: 10.1186/s12933-020-01122-4.
citation: Aubert CE, Liabeuf S, Amouyal C, Kemel S, Lajat-Kiss F, Lacorte JM, Halbron M, Carlier A, Salem JE, Funck-Brentano C, Perisic Matic L, Witasp A, Stenvinkel P, Phan F, Massy ZA, Hartemann A, Bourron O. Serum concentration and vascular expression of adiponectin are differentially associated with the diabetic calcifying peripheral arteriopathy. Diabetol Metab Syndr. 2019 Apr 29;11:32. doi: 10.1186/s13098-019-0429-7. eCollection 2019.