NCT03433820已完成不适用

A Single-arm, Observational Study to Explore and Characterize Wound Healing After Skin Punch Biopsies in Healthy Volunteers

Centre for Human Drug Research, Netherlands2 个研究点分布在 1 个国家目标入组 18 人开始时间: 2017年10月26日最近更新: 2021年8月3日

研究概览

简要总结

The skin plays a critical role in protection where it acts as a barrier from damage and pathogens between the external and internal environments. Wounds compromise its protective role by disrupting the function and the normal structure of the skin and the underlying soft tissue. As a response to injury wound healing occurs in order to rapidly restore the defect. This process involves activation of keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets and consists of multiple phases including hemostasis, inflammation, migration and cellular proliferation, and maturation and remodeling. A simplified schematic of the course of wound healing is depicted in Figure 2. Hemostasis occurs immediately after dermal injury. The inflammation phase is characterized by cellular recruitment and increased vascular permeability. The epithelization phase is achieved by proliferation of basal cells and migration of epithelial cells. The last phase is known as the maturation and remodeling phase where collagen cross-linking and remodeling, wound contraction, and repigmentation takes place. Due to the broad involvement of various cell types, extracellular matrix and many reactive molecules each phase in wound healing produces characteristic changes within the tissue. A deficiency in any part of the process can lead to delayed wound healing, abnormal scar formation or chronic wounds.

To study wound healing in healthy volunteers a challenge model with skin punch biopsies has been described in literature previously. However, the characterization of this model was not performed comprehensively since advanced analysis of biopsies were omitted. Furthermore, analyses performed in previous studies only partially described wound healing processes either by insufficient time points for characterization or scarce simultaneous evaluations of multiple wound healing modalities.

The overall aim of this study is to develop a standardized model to temporarily and locally induce a skin trauma to investigate wound healing and monitor wound closure. This clinical model will enable future application as proof-of-pharmacology and proof-of concept studies as well as drug profiling in early drug development programs. More specifically, the objective of the trial is to explore and characterize the induction of well-defined skin trauma and natural wound healing process over the course of the different phases using a battery of dermatological assessments after skin punch biopsies in healthy volunteers. Furthermore, safety and tolerability will be assessed.

Characterization and monitoring of wound healing effects following skin punch biopsies will be performed by means of biophysical, biochemical, imaging, clinical parameters and subject reported outcomes.

详细描述

Background & Rationale The skin plays a critical role in protection where it acts as a barrier from damage and pathogens between the external and internal environments. Wounds compromise its protective role by disrupting the function and the normal structure of the skin and the underlying soft tissue. As a response to injury wound healing occurs in order to rapidly restore the defect. This process involves activation of, among others, keratinocytes, fibroblasts, endothelial cells, macrophages, and platelets and consists of multiple phases including hemostasis, inflammation, migration and cellular proliferation, and maturation and remodeling. A simplified schematic of the course of wound healing is depicted in Figure 2. Due to the broad involvement of various cell types, extracellular matrix and many reactive molecules each phase in wound healing produces characteristic changes within the tissue. A deficiency in any part of the process can lead to delayed wound healing, abnormal scar formation or chronic wounds.

To study wound healing in healthy volunteers a challenge model with skin punch biopsies has been described in literature previously. However, the characterization of this model was not performed comprehensively since advanced analysis of biopsies were omitted. Furthermore, analyses performed in previous studies only partially described wound healing processes either by insufficient time points for characterization or scarce simultaneous evaluations of multiple wound healing modalities. In addition, novel non-invasive imaging methodologies including thermography, 3D photography, multispectral imaging, enable more comprehensive profiling of the wound morphology.

The overall aim of this study is to develop a standardized model to temporarily and locally induce a skin trauma to investigate wound healing and monitor wound closure. This clinical model will enable future application as proof-of-pharmacology and proof-of concept studies as well as drug profiling in early drug development programs. More specifically, the objective of the trial is to explore and characterize the induction of well-defined skin trauma and natural wound healing process over the course of the different phases using a battery of dermatological assessments after skin punch biopsies in healthy volunteers. Furthermore, safety and tolerability will be assessed.

Characterization and monitoring of wound healing effects following skin punch biopsies will be performed by means of biophysical, biochemical, imaging, clinical parameters and subject reported outcomes.

Objective(s) Primary Objective

研究设计

研究类型: Interventional
分配方式: Randomized
干预模型: Single Group
主要目的: Diagnostic
盲法: None

入排标准

年龄范围: 18 Years 至 30 Years（Adult）
性别: All
接受健康志愿者: 是

入选标准

•Eligible subjects must meet all of the following inclusion criteria at screening:
•Healthy subjects, 18 to 30 years of age (inclusive). The health status is verified by absence of evidence of any clinical significant active or uncontrolled chronic disease following a detailed medical history, a complete physical examination including vital signs, blood sampling of hematology, chemistry, and virology, urinalysis, urine drug and cotinine testing, and alcohol breath testing. In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects.
•Body mass index (BMI) between 18 and 30 kg/m2, inclusive
•Fitzpatrick Skin type I-II (Caucasian type).
•Eligible lower back to perform biopsies (no excessive hair growth, no local skin disorder)
•Willing to give written informed consent and willing and able to comply with the study protocol.

排除标准

•Eligible subjects must meet none of the following exclusion criteria at screening:
•History of pathological scar formation (keloid, hypertrophic scars)
•Any form of body modification of the lower back hindering biopsy collection of unaltered skin (e.g. tattoos, piercings, implants)
•Any disease associated with immune system impairment, including auto-immune diseases, HIV and transplantation patients.
•Requirement of immunosuppressive or immunomodulatory medication, including glucocorticoids, non-steroid anti-inflammatory drugs (NSAIDs), and chemotherapeutic drugs within 30 days prior to enrollment or planned to use during the course of the study.
•Have any current and/or recurrent pathologically, clinical significant relevant skin condition.
•Use of topical medication (prescription or over-the-counter (OTC)) within 30 days of the start of the study.in local treatment area.
•Pregnant, a positive pregnancy test, intending to become pregnant, or breastfeeding.
•Current smoker and/or regular user of other nicotine-containing products (e.g., patches).
•Average consumption of more than 14 units of alcohol per week
•Tanning due to sunbathing, excessive sun exposure or a tanning booth within 3 weeks of enrollment or planned to do so during the course of the study
•Participation in an investigational drug or device study within 3 months prior to screening or more than 4 times a year.
•Loss or donation of blood over 500 mL within three months prior to screening.
•Any (medical) condition that would, in the opinion of the investigator, potentially compromise the safety or compliance of the subject or may preclude the subjects' successful completion of the clinical trial.