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

NCT ID: NCT04983654

Last Updated: 2025-12-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-09
• Study Completion Date: 2023-10-03

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.

Conditions

Ulcer; Anemia; Sickle Cell Disease

Keywords

limb ulcers; sickle cell disease; microcirculation; cytokine; wound fluid

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Patients with limb ulcer

Patients with sickle cell disease and suffering from limb ulcer

Group Type: EXPERIMENTAL

patients with limb ulcers

Intervention Type: DIAGNOSTIC_TEST

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

Patients without limb ulcer

Patients with sickle cell disease without any limb ulcer

Group Type: EXPERIMENTAL

For patients without limb ulcers

Intervention Type: DIAGNOSTIC_TEST

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

Interventions

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

Intervention Type: DIAGNOSTIC_TEST

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

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospices Civils de Lyon

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Judith CATELLA, Dr

Role: PRINCIPAL_INVESTIGATOR

Service de Médecine Interne

Locations

Groupement Hospitalier Edouard Herriot

Lyon, , France

Countries

France

References

Catella J, Turpin E, Connes P, Nader E, Carin R, Martin M, Rezigue H, Nougier C, Dargaud Y, Josset-Lamaugarny A, Dugrain J, Marano M, Leuci A, Boisson C, Renoux C, Joly P, Poutrel S, Hot A, Guillot N, Fromy B. Impaired microvascular function in patients with sickle cell anemia and leg ulcers improved with healing. Br J Haematol. 2024 Dec;205(6):2459-2469. doi: 10.1111/bjh.19785. Epub 2024 Sep 24.

Reference Type: RESULT

PMID: 39318045 (View on PubMed)

Other Identifiers

69HCL21_0305

Identifier Type: -

Identifier Source: org_study_id

2021-A01605-36

Identifier Type: OTHER

Identifier Source: secondary_id