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

Anemia Clinical Trial

— DrepanO2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04983654
• Other study ID #: 69HCL21_0305
• Secondary ID: 2021-A01605-36
• Status: Completed
• Phase: N/A
• Start date: February 9, 2022
• Est. completion date: October 3, 2023

Study information

• Verified date: October 2023
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 70
• Est. completion date: October 3, 2023
• Est. primary completion date: October 3, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 130 Years

Eligibility

Inclusion Criteria:

• Sickle Cell Disease (homozygous SS or Sb0)

• Age = 18 years old

• Consent patients

• Social regimen

Exclusion Criteria:

• tutela or curatella

• Vaso occlusive crisis < 1 month

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell
• Sickle Cell Disease
• Ulcer

Intervention

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: Microvascular analysis (laser doppler, TcPO2), Neurological analysis ( sensitivity testing with thermal and mechanical test), Analysis of physical characteristics of red blood cells and inflammatory marks, Analysis of cytokine and metalloproteases in the wound fluid, Assessment of healing according usual treatment
• For patients without limb ulcers
For patients without limb ulcers : at inclusion visit only Microvascular analysis (laser doppler, TcPO2), Neurological analysis (sensitivity testing with thermal and mechanical test), Analysis of physical characteristics of red blood cells and inflammatory marks

Locations

Country	Name	City	State
France	Groupement Hospitalier Edouard Herriot	Lyon

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Alteration of cutaneous microvascular function and peripheral sensorial neurological function in patients with limb ulcers	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.	Day 1
Secondary	Modification of hemorheological red blood cells characteristics between patients with and without ulcers	Analysis of hemorheological characteristics in the 2 arms after blood test with blood viscosity and RBC rheological measurements (deformability/aggregation)	Day 1
Secondary	Analysis of the composition of the wound fluid	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	Day 1
Secondary	Compare pro inflammatory markers in the blood between patients with and without ulcers	Analysis of inflammatory markers in the blood and comparison between the 2 arms	At initial visit
Secondary	Assessment of healing	Delay of granulation tissue appearance, delay of healing according treatment used	through study completion, an average of 6 months
Secondary	Compare microcirculation, pro inflammatory marker in the wound fluid and in the blood and hemorheological characteristics after usual treatment to obtain healing	Compare results (previously described) in the group of patients with ulcers, between initial and second visit	through study completion, an average of 6 months