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

NCT04983654 | Completed

• 2 other identifiers: 69HCL21_03052021-A01605-36
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Modification of hemorheological red blood cells characteristics between patients with and without ulcers

  Day 1

• Analysis of the composition of the wound fluid

  Day 1

• Compare pro inflammatory markers in the blood between patients with and without ulcers

  At initial visit

• Assessment of healing

  through study completion, an average of 6 months

• 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

Study Arms (2)

Patients with limb ulcer

EXPERIMENTAL

Patients with sickle cell disease and suffering from limb ulcer

Diagnostic Test: patients with limb ulcers

Patients without limb ulcer

EXPERIMENTAL

Patients with sickle cell disease without any limb ulcer

Diagnostic Test: For patients without limb ulcers

Interventions

patients with limb ulcers 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 with limb ulcer

For patients without limb ulcers 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

Patients without limb ulcer

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• tutela or curatella
• Vaso occlusive crisis \< 1 month

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Groupement Hospitalier Edouard Herriot

Lyon, 69437, France

Location

Related Publications (1)

• 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.

  PMID: 39318045 RESULT

MeSH Terms

Conditions

Ulcer; Anemia; Anemia, Sickle Cell

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Judith CATELLA, Dr

  Service de Médecine Interne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2021
• First Posted: July 30, 2021
• Study Start: February 9, 2022
• Primary Completion: October 3, 2023
• Study Completion: October 3, 2023
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (1)