Arterial Calcification in the Diabetes

NCT ID: NCT02431234

Last Updated: 2018-06-04

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 169 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-02-28
• Study Completion Date: 2018-09-30

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

Conditions

Diabetic Vascular Diseases; Arteriosclerosis Obliterans; Monckeberg Medial Calcific Sclerosis

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Interventions

serum RANKL

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

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

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Olivier Bourron, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Groupe Hospitalier Pitié Salpetrière

Paris, , France

Countries

France

References

Denimal D, Ponnaiah M, Phan F, Jeannin AC, Redheuil A, Salem JE, Boussouar S, Paulstephenraj P, Laroche S, Amouyal C, Hartemann A, Foufelle F, Bourron O. Metabolic dysfunction-associated steatotic liver disease (MASLD) biomarkers and progression of lower limb arterial calcification in patients with type 2 diabetes: a prospective cohort study. Cardiovasc Diabetol. 2025 Apr 23;24(1):176. doi: 10.1186/s12933-025-02705-9.

Reference Type: DERIVED

PMID: 40269920 (View on PubMed)

Le Goff W, Bourron O, Materne C, Galier S, Phan F, Tan-Chen S, Guillas I, Hartemann A, Salem JE, Redheuil A, Foufelle F, Le Stunff H, Hajduch E, Guerin M. Inverse relationship between circulating sphingosine-1-phosphate and precursor species and coronary artery calcification score in type 2 diabetes. Cardiovasc Diabetol. 2025 Feb 21;24(1):85. doi: 10.1186/s12933-025-02624-9.

Reference Type: DERIVED

PMID: 39984928 (View on PubMed)

Denimal D, Ponnaiah M, Jeannin AC, Phan F, Hartemann A, Boussouar S, Charpentier E, Redheuil A, Foufelle F, Bourron O. Non-alcoholic fatty liver disease biomarkers estimate cardiovascular risk based on coronary artery calcium score in type 2 diabetes: a cross-sectional study with two independent cohorts. Cardiovasc Diabetol. 2024 Feb 13;23(1):69. doi: 10.1186/s12933-024-02161-x.

Reference Type: DERIVED

PMID: 38351039 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33377125 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32948184 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31168327 (View on PubMed)

Other Identifiers

P111105

Identifier Type: -

Identifier Source: org_study_id