Contrast Enhanced Ultrasound and Muscle

Brief Title

Contrast Enhanced Ultrasound and Muscle

Official Title

Echographie de Contraste Pour l'Analyse de la Perfusion Musculaire Dans l'ischémie Critique

Brief Summary

      The primary objective of our work is to show that quantification of muscular
      microvascularisation evaluated by injection of contrast agent is different between chronic
      critical limb ischemia (before revascularization) and after (healing of ischemia) and thus
      make the proof of its utility in evaluation of PAD therapeutics.
    

Detailed Description

      -  Peripheral arterial disease (PAD) is a frequent disease the incidence of which in men is
           about 32.5°/°° before 40 years and 71°/°° after 50 years. Prevalence of the disease
           increases with age to reach 3.7% of 60 to 69 year old subjects (Kannel 1970, 1985, Bloch
           1985).

        -  Critical limb ischemia (CLI) ischemia is defined by typical chronic ischemic rest pain
           or ischemic skin lesions either ulcers or gangrene for more than two weeks (Norgren).
           Incidence is about 500 - 1000 / 106 / year in Europe and United states. Critical limb
           ischemia concerns 15 - 20% of patients with intermittent claudication (Eneroth 1992,
           Taylor 1989). Development can lead to limb loss with a frequency estimated between 7% at
           5 years to 12% at 10 years. Problem is crucial for patients who cannot benefit from
           revascularization. Results of single medical treatments are uncertain. Development of
           neovascularisation by innovating therapeutic (autolog cell stem grafts, intramuscular
           growth factor injections ) represent an exciting and promising field of research.

        -  Peripheral arterial disease evaluation and staging are based on measures of resting
           ankle pressures, diagnosis of stenosis and obliteration (duplex, angiography, computed
           tomography scan and magnetic resonance imaging) and on measure of microcirculatory skin
           perfusion by Tc PO2. On the other hand, there is no simple tool to measure muscular
           microvascularisation whereas muscles suffer from ischemia in the same way as skin and
           nerves. Measures of muscular perfusion can be performed by Tc 99, magnetic resonance
           imaging but this is not used in clinical practice. CEUS used in routine to assess
           hepatic microvascularisation has recently been shown to be potentially useful to study
           muscle (Kramer 2008, Weber 2007).

        -  Ultrasonic contrast agents are intravascular microbubbles which used at low mechanical
           index generate harmonics and allow real time imaging in ultrasonography. Their use
           allows study of parenchyma enhancement in real time, notably of liver and kidneys; they
           are also used in practice to differentiate benign and malign tumors (Correas 2009).
           Correlations have been shown between muscle enhancement studied by CEUS and histologic
           data of capillary vascularisation (Weber 2005). More recently some authors have shown
           that CEUS may allow to differentiate patients with PAD at a stage of intermittent
           claudication and patients without PAD (Duerschmied 2006).Very few studies have studied
           patients with CLI. Duerschmied and all have shown that kinetic data of muscle
           enhancement may reflect collateral circulation developed in reaction to chronic
           ischemia. CEUS may be used to study muscular perfusion in the same way as TcPO2 reflects
           cutaneous vascularisation and may become an evaluation criteria of PAD therapeutics in a
           near future.

        -  We propose to study muscular perfusion by CEUS in patients with critical limb ischemia
           eligible to revascularization (PTA or bypass) before and after revascularization.
           Microbubbles injection leads to an increase in muscle echogenicity in two sequences: a
           rapid phase 15-20 s after injection (arteriolar filling) then a more intense second
           phase (veinular and capillary filling) (Duerschmied 2006). These two phases may be
           described by measures of acoustic intensity function of time and in particular time to
           peak (TTP), area under the curve (AUC). Time to peak seems to be the more reliable
           criteria (Duerschmied).
    


Study Type

Interventional


Primary Outcome

Time to Peak

Secondary Outcome

 Curves datas

Condition

Ischemia

Intervention

contrast echographie with hexafluorur of sulfur

Study Arms / Comparison Groups

 revascularization group
Description:  Subjects in this arms have an contrast echographie with sonovue(r) then a revascularization and finnaly an other contrast echographie with sonovue.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Other

Estimated Enrollment

32

Start Date

February 2011

Completion Date

March 2014

Primary Completion Date

March 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Men and women over 40 years

          -  Patients with chronic critical limb ischemia as defined by consensus TASC 2 and
             eligible to a revascularisation

          -  Objective evaluation of critical ischemia is based on ankle pressure < 70 mm Hg or toe
             pressure < 50 mm Hg for patients with ulcer or pressure ankle pressure < 50 mm Hg or
             toe pressure < 30 mm Hg for patients with rest pain.

          -  Patient's consent signed

        Exclusion Criteria:

          -  Patients under 18

          -  Pregnant or breast feeding woman

          -  Burger's disease

          -  Contra- indication to use of contrast

               -  Hypersensitivity to sulfurhexafluorure

               -  Unstable coronary heart disease, acute stroke, uncompensated heart failure

               -  Right to left shunt

               -  Serious pulmonary hypertension (> 90 mm Hg)

               -  Uncontroled increased blood pressure

               -  Acute respiratory distress syndrom

          -  Consent refused

          -  Patients with leg wounds preventing ultrasonography
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Christophe Seinturier, Doctor, , 

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT02128750

Organization ID

EBCS1


Responsible Party

Sponsor

Study Sponsor

University Hospital, Grenoble


Study Sponsor

Christophe Seinturier, Doctor, Principal Investigator, University Hospital Grenoble - Medecine vasculaire


Verification Date

April 2014