Functional and Mechanistic Characterization of Limb Ulcers in Patients With Sickle Cell Disease (DrepanO2)
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|ClinicalTrials.gov Identifier: NCT04983654|
Recruitment Status : Recruiting
First Posted : July 30, 2021
Last Update Posted : March 3, 2022
Sickle Cell Disease is the most frequent genetic disease in the world (representing one birth over 1900, in France). The polymerization of the abnormal hemoglobin (i.e., HbS) when deoxygenated is at the origin of a mechanical distortion of red blood cells (RBC) into a crescent-like shape. Sickled RBCs are very fragile and rigid, which lead patients to have severe anemia and to develop frequent and repeated painful vaso-occlusive crises. Furthermore, the repetition of sickling-unsickling cycles causes irreversible damages to the RBCs, which shorten their half-life. Accumulation of free hemoglobin and heme in the plasma is involved in blood vessels lesions in both the macro- and micro- circulation.
The resulting vascular dysfunction could explain why limb ulcers are 10 fold more frequent in patients with sickle cell disease compared to the general population and may happen at a younger age. Limb ulcers induce significant morbidity (delay of healing between 9 and 26 weeks in the french cohort), and are associated to significant pain (needing opioid pain-killer) and increase the risk of infection. Cost of care is also increased. Moreover, ulcers induce missed school and work days.
Data on cutaneous microcirculation and ulcers physiopathology in patients with sickle cell disease are scarce. We want to realise a microcirculatory and neurological functional study of patients with with and without ulcers and a characterization of biomarkers present in the blood or in the wound fluid which can participate to ulcers physiopathology.
To ensure healing, adapted therapeutics are essential. Several strategies are proposed such as: lifestyle measures (venous compression, lower limb elevation, rest), dressings, hyperbaric oxygenotherapy (also used in diabetic ulcers). The project is devoted to study the mechanisms involved in leg ulcers and the effects of therapeutical/behavioral strategies.
|Condition or disease||Intervention/treatment||Phase|
|Ulcer Anemia Sickle Cell Disease||Diagnostic Test: patients with limb ulcers Diagnostic Test: For patients without limb ulcers||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||70 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Primary Purpose:||Basic Science|
|Official Title:||Functional and Mechanistic Characterization of Limb Ulcers in Patients With Sickle Cell Disease|
|Actual Study Start Date :||February 9, 2022|
|Estimated Primary Completion Date :||January 1, 2024|
|Estimated Study Completion Date :||January 1, 2024|
Experimental: Patients with limb ulcer
Patients with sickle cell disease and suffering from limb ulcer
Diagnostic Test: patients with limb ulcers
For patients with limb ulcers : at inclusion visit and after healing or at 6 months if ulcer does not heal:
Experimental: Patients without limb ulcer
Patients with sickle cell disease without any limb ulcer
Diagnostic Test: For patients without limb ulcers
For patients without limb ulcers : at inclusion visit only
- Alteration of cutaneous microvascular function and peripheral sensorial neurological function in patients with limb ulcers [ Time Frame: Day 1 ]
Cutaneous microvascular function is assessed with :
- laser Doppler Including measurement of blood pressure before and after testing, heart rate before and after testing, cutaneous temperature, values of laser Doppler before and after vasodilatation with acetylcholine, deionized water, local heating (42°C)
- TcPO2 on the first intermetatarsal space and bordering ulcer Peripheral sensorial neurological function is assessed with Von Frey monofilament, hot (50°C)/cold (4°C) test, pic-touch test and pallesthesia.
- Modification of hemorheological red blood cells characteristics between patients with and without ulcers [ Time Frame: Day 1 ]Analysis of hemorheological characteristics in the 2 arms after blood test with blood viscosity and RBC rheological measurements (deformability/aggregation)
- Analysis of the composition of the wound fluid [ Time Frame: Day 1 ]Analysis of metalloproteases (MMP-8 and MMP-9) and inflammatory markers (TNF-alpha, Il-6, Il1-beta, VCAM 1, P-selectin) in the wound fluid
- Compare pro inflammatory markers in the blood between patients with and without ulcers [ Time Frame: At initial visit ]Analysis of inflammatory markers in the blood and comparison between the 2 arms
- Assessment of healing [ Time Frame: through study completion, an average of 6 months ]Delay of granulation tissue appearance, delay of healing according treatment used
- Compare microcirculation, pro inflammatory marker in the wound fluid and in the blood and hemorheological characteristics after usual treatment to obtain healing [ Time Frame: through study completion, an average of 6 months ]Compare results (previously described) in the group of patients with ulcers, between initial and second visit
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04983654
|Contact: Judith CATELLA, Dr||04 72 11 77 91 ext +firstname.lastname@example.org|
|Groupement Hospitalier Edouard Herriot||Recruiting|
|Lyon, France, 69437|
|Contact: Judith CATELLA, Dr 04 72 11 77 91 email@example.com|
|Principal Investigator:||Judith CATELLA, Dr||Service de Médecine Interne|