Functional and Mechanistic Characterization of Limb Ulcers in Patients With Sickle Cell Disease

Not Applicable

Completed

• Conditions: Anemia; Ulcer; Sickle Cell Disease
• Interventions: Diagnostic Test: patients with limb ulcers; Diagnostic Test: For patients without limb ulcers

• Registration Number: NCT04983654
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2021-07-13
• Study First Submitted QC: 2021-07-20
• Study First Posted: 2021-07-30
• Study Start: 2022-02-09
• Status Verified: 2023-10
• Primary Completion: 2023-10-03
• Study Completion: 2023-10-03
• Last Update Submitted: 2023-10-06
• Last Update Posted: 2023-10-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• Sickle Cell Disease (homozygous SS or Sb0)
• Age ≥ 18 years old
• Consent patients
• Social regimen

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Exclusion Criteria

• tutela or curatella
• Vaso occlusive crisis < 1 month

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients with limb ulcer	patients with limb ulcers	Patients with sickle cell disease and suffering from limb ulcer
Patients without limb ulcer	For patients without limb ulcers	Patients with sickle cell disease without any limb ulcer

Primary Outcome Measures

Name	Time	Method
Alteration of cutaneous microvascular function and peripheral sensorial neurological function in patients with limb ulcers	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.

Secondary Outcome Measures

Name	Time	Method
Analysis of the composition of the wound fluid	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 microcirculation, pro inflammatory marker in the wound fluid and in the blood and hemorheological characteristics after usual treatment to obtain healing	through study completion, an average of 6 months	Compare results (previously described) in the group of patients with ulcers, between initial and second visit
Modification of hemorheological red blood cells characteristics between patients with and without ulcers	Day 1	Analysis of hemorheological characteristics in the 2 arms after blood test with blood viscosity and RBC rheological measurements (deformability/aggregation)
Compare pro inflammatory markers in the blood between patients with and without ulcers	At initial visit	Analysis of inflammatory markers in the blood and comparison between the 2 arms
Assessment of healing	through study completion, an average of 6 months	Delay of granulation tissue appearance, delay of healing according treatment used

Trial Locations

Locations (1)

Groupement Hospitalier Edouard Herriot; 🇫🇷 Lyon, France