Circulating Anti-Beta2-glycoprotein Antibodies and Endothelial Dysfunction

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Joaquin de Haro, M.D., Hospital Universitario Getafe
ClinicalTrials.gov Identifier:
NCT01822990
First received: March 26, 2013
Last updated: March 28, 2013
Last verified: March 2013
  Purpose

Circulating anti-beta2-glycoprotein antibodies have been associated with coronary artery disease and peripheral arterial disease. This auto-antibodies could activate endothelial cells leading to the expression of leukocyte adhesion molecules and increasing the release of pro-inflammatory cytokines.

On the other hand, endothelial dysfunction of atherosclerotic patients acts as a primary pathogenic event, as it occur before structural changes are evident on angiogram or ultrasound scan. Loss of endothelial normal function causes vasoconstriction, local coagulation alterations and an increase arterial wall proliferation. This situation s been attributed to a reduction in nitric oxide bioactivity, and to an increase oxygen-free radical formation in the context of the pro-inflammatory status found in atherosclerosis.

Hypothesis: Circulating Anti-beta2-glycoprotein I antibodies could be associated with endothelial dysfunction and nitric oxide metabolism disruption en patients with peripheral arterial disease.


Condition
Peripheral Arterial Disease

Study Type: Observational [Patient Registry]
Study Design: Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration: 12 Months
Official Title: Influence of Circulating Anti-beta2-glycoprotein I Antibodies on the Endothelial Function and NO Metabolism in Peripheral Arterial Disease Patients.

Resource links provided by NLM:


Further study details as provided by Hospital Universitario Getafe:

Primary Outcome Measures:
  • Circulating anti-beta2-glycoprotein I antibodies [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    The titer of circulating anti-endothelial cell antibodies directed against beta2-glycoprotein antigens (Circulating ABGPI) could be detected by indirect immunofluorescence using a diagnosis reagent kit and subjects serum.

  • Flow-mediated arterial dilatation (FMAD) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    FMAD is an ultrasound test based on the ability of endothelial cells to detect changes in shear stress and is one of the most effective and reliable indirect methods for estimating endothelial dysfunction. The ultrasound transducer is applied proximal to the antecubital fossa, and a longitudinal image of the brachial artery is obtained. The basal arterial diameter is determined. A blood pressure cuff is then placed distal to the measurement area and inflated to a pressure of 250 mmHg for five minutes. New measurements of the arterial diameter in the final diastolic phase should be obtained, 60 seconds after the cuff is deflated

  • Nitrite serum levels [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Nitrite serum levels reflects the nitric oxide metabolism. Serum nitrite concentration could be measured by colorimetric analysis using the Griess reaction. This is a chemical reaction which uses sulphanilamide and naphthylethylenediamine dihydrochloride under acid conditions (phosphoric acid).The system is capable of detecting nitric oxide in a variety of biological and experimental fluids, like human serum samples.

  • Highly sensitive C-reactive protein. [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Highly sensitive C-reactive protein levels could be measured using a highly sensitive, automated immunoassay with the human serum samples.


Biospecimen Retention:   Samples Without DNA

Serum samples of all the subjects included.


Enrollment: 60
Study Start Date: February 2011
Study Completion Date: July 2012
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts
Atherosclerotic patients
Male patients with intermittent claudication.
Control subjects
healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who are not in receipt of any pharmacological treatment, matched by age within two years with peripheral arterial disease patients

  Eligibility

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Cases: Male patients with intermittent claudication due to peripheral arterial disease after haemodynamic confirmation of the disease by Doppler and treadmill exercise testing. No previous history of autoimmune disease.

Controls: Healthy male subjects with normal results on vascular examination and no cardiovascular risk factors, who were not in receipt of any pharmacological treatment, matched by age within two years with PAD patients.

Criteria

Inclusion Criteria:

  • Male gender
  • Peripheral arterial disease diagnosis
  • Intermittent claudication.
  • Hemodynamic confirmation of the disease through non-invasive vascular studies.

Exclusion Criteria:

  • Autoimmune disease
  • Previous revascularization of the ischemic limb.
  • Ischemic ulcers
  • Previous history of organ transplants.
  • Treatment with immunosuppressors
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01822990

Locations
Spain
Hospital Universitario de Getafe
Getafe, Madrid, Spain, 28905
Sponsors and Collaborators
Hospital Universitario Getafe
Investigators
Principal Investigator: Cesar Varela, MD Hospital Universitario de Getafe
Study Director: Joaquin De Haro, MD Hospital Universitario de Getafe
Study Director: Francisco Acin, MD, PhD Hospital Universitario de Getafe
  More Information

No publications provided

Responsible Party: Joaquin de Haro, M.D., Study director, Hospital Universitario Getafe
ClinicalTrials.gov Identifier: NCT01822990     History of Changes
Other Study ID Numbers: ABGPINO150613
Study First Received: March 26, 2013
Last Updated: March 28, 2013
Health Authority: Spain: Ministry of Health

Keywords provided by Hospital Universitario Getafe:
Anti-beta2-glycoprotein antibodies
Peripheral arterial disease
Inflammation
Nitric oxide
Endothelial dysfunction

Additional relevant MeSH terms:
Peripheral Arterial Disease
Peripheral Vascular Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Antibodies
Krestin
Beta 2-Glycoprotein I
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Anticoagulants
Hematologic Agents
Therapeutic Uses
Adjuvants, Immunologic
Antibiotics, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Interferon Inducers
Radiation-Protective Agents
Protective Agents

ClinicalTrials.gov processed this record on September 30, 2014