Immune Cells in Diabetic Chronic Foot Ulcers

Karolinska Institute

Status: Enrolling

Conditions: Diabetic Foot; Immune Defect

Treatments: Other: medical treatments

Study type: Observational

Funder types: Other

Identifiers

NCT06154915

2022-01416

Details and patient eligibility

About

The goal of this observational study is to learn about the role of immune cells in patients with diabetes and chronic foot ulcers. Researchers will compare blood and tissue samples of patients with diabetes and a foot ulcer that is healing or healed compared to those diabetic patients where the foot ulcers is not healing (chronic ulcer).

Full description

Diabetic foot ulcer (DFU) requires frequent hospital visits, anti-biotic therapies, and surgical procedures. Not only this approach has debilitating consequences for patients and enormous costs for the health care system, but it is often not sufficient to prevent lower limb amputation. The immunological response in wound healing is mainly orchestrated by recruited monocytes and skin macrophages. The current hypothesis is that hyperglycaemia sustains an activated macrophages' phenotype that inhibits wound healing. However, well controlled diabetes is not associated with better healing, and not all the diabetic patients develop chronic foot ulcers. In this project, the investigators aim to characterize the immunological response of patients with DFU to discover new therapeutic targets for the treatment of chronic wounds. The investigator suggest that an altered metabolic local environment can re-program monocytes/macrophages towards dysfunctional phenotypes unable to accomplish the healing process. Here, by using a longitudinal study cohort combined with clinical information, transcriptomic and proteomic analysis at single cell level, researchers will characterize the landscape of monocytes/macrophage populations involved in healing, and non-healing, foot ulcers. Functional validation will be performed in human skin organoids. My group's unique access to patient material combined with cutting-edge methodologies provides an exceptional platform to identify genes and pathways involved in chronic DFU.

Enrollment: 40 estimated patients

Sex: All

Ages: 18 to 98 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• diabetes with diabetic foot ulcer

Exclusion criteria

• impaired cognitive function
• on-going immune suppressive treatment
• diagnosed active cancer
• cancer treatment
• known chronic inflammatory disease

Trial design

40 participants in 2 patient groups

Healing Ulcer

Description:

The patients will be recruited from the doctors and the nurses of the foot clinic of Department of Endocrinology. A complete medical history and physical parameters will be collected, moreover a peripheral circulation status will assess at the time of the enrolment. During the first visit blood samples and a biopsy from the site of foot ulcers will be taken together with a picture of the ulcer. All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding). Intervals between visits will range between 4 to 8 weeks according to the usual medical routine. During visits 1, 2 and 3 the ulcers status will be documented by pictures, physical parameter collected, biopsies, ulcer fluid and blood samples will be taken for further analysis. At visit 3 the ulcers will be classified as "healing" if completely resolved or dramatically reduced (more than 50%), otherwise will be classified as "non-healing".

Treatment:

Other: medical treatments

Non-Healing Ulcer

Description:

The patients will be recruited from the doctors and the nurses of the foot clinic of Department of Endocrinology. A complete medical history and physical parameters will be collected, moreover a peripheral circulation status will assess at the time of the enrolment. During the first visit blood samples and a biopsy from the site of foot ulcers will be taken together with a picture of the ulcer. All patients will follow the medical treatments, as recommended by the multidisciplinary clinical team (for example revascularization or ulcer debriding). Intervals between visits will range between 4 to 8 weeks according to the usual medical routine. During visits 1, 2 and 3 the ulcers status will be documented by pictures, physical parameter collected, biopsies, ulcer fluid and blood samples will be taken for further analysis. At visit 3 the ulcers will be classified as "non-healing" if not resolved or not dramatically reduced (more than 50%).

Treatment:

Other: medical treatments