Clinical trial NCT04736251: Mechanistic Basis of Ablative Carbon Dioxide Laser in Treating Hypertrophic Scars
Official title: A Prospective Intra-patient Single-blinded Randomised Trial to Examine the Mechanistic Basis of fractiOnal Ablative carbOn Dioxide Laser Therapy in Treating Adult Burns and/or Trauma Patients With Hypertrophic Scarring
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Burn Scar
Scar
Lead sponsor: University Hospital Birmingham NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: The Scar Free Foundation Centre for Conflict Wound Research
name: University of Birmingham
name: Welsh Centre for Burns and Plastic Surgery, Morriston Hospital
First posted: 2021-02-03
Enrollment: 60
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patient with hypertrophic scarring as a result of deep dermal or full thickness burns/trauma sustained more than 12 months prior to recruitment.

Brief summary: This is an observational cohort study which will look at the biomarkers from blood and tissue sample for adult patients with hypertrophic scarring due to burns/trauma incident over 12 months from date of recruitment. The study will assess the kinetics of the response to fractionated carbon dioxide laser therapy in hypertrophic scars.

Detailed description: Research has identified a gap in the knowledge of how fractional ablative carbon dioxide laser works on hypertrophic (thickened) scars. At present there is no accurate measure of how effective the benefit is objectively (medically), subjectively (to the patient) and histologically (on a microscopic level). Recent systematic review has shown an improvement in scars following laser therapy, however it found the quality of the data to be poor, confounded by multiple bias, identifying the lack of evidence to prove the worth and effectiveness of lasers. It concluded the need for more robust studies.

The study plans to observe a group of patients with hypertrophic burn and/or trauma scars (over 1 year old) and see what happens to their scars using the fractionated carbon dioxide laser therapy. Two similar scars will be identified per patient volunteer and will randomly allocate to receive either fractionated carbon dioxide laser therapy or standard care. An independent assessor will be blinded to the intervention and control scar sites.

The trial will aim to identify any biological markers found in participants blood and scar tissue and if they change through the course of and following laser therapy. This will help with understanding the mechanism of how the carbon dioxide laser works on scars.

As part of the evaluation of the impact of laser treatment on patients' quality of life, a patient reported outcome measures (PROMS) validation study will be carried out. PROMs describe how the patient is functioning or feeling without input from clinical staff providing a unique perspective of patients' lived experience of the disease as not all symptoms or impacts are obvious to clinicians. In order for PROMs to be effective in clinical trials and practice, they have to capture information on domains that matter to the patient. These include: scarring, movement and function, scar sensation, psychological distress, body image and confidence, engagement in activities, treatment burden and impact on relationships.

The scars will be assessed in a number of different ways; scar assessment tools/questionnaires, clinical inspection, photography, use of ultrasound, probes with suction to test the elasticity and pliability of the scars and the colour, microscopic evaluation and the identification of biomarkers from blood samples and scar and normal tissue biopsy.

Eligibility criteria: Inclusion Criteria:

* Adult patients aged ≥ 16years
* Patient with hypertrophic scarring as a result of deep dermal or full thickness burns/trauma.
* Trauma or Burn sustained more than 12 months prior to recruitment.
* Treatment area to be ≥25cm2 confluent scarring with a comparable control scar on limb or trunk

General Exclusion Criteria:

* Patients under 16 years of age
* Previous laser therapy treatment to the study site
* The use of recent (within 6 months) or concurrent invasive scar treatments, including intra-lesional pharmaceuticals, micro needling or other laser modalities (e.g. Pulse-dye.)
* Known allergy or contraindication to EMLA™ 5% Cream (Lidocaine 2.5% and Prilocaine 2.5%), Dermol 500TM (Benzalkonium Chloride 0.1%; Chlorhexidine Dihydrochloride 0.1%; Liquid Paraffin 2.5%; Isopropyl Myristate 2.5%) or 50:50 ointment (White Soft Paraffin Liquid Paraffin %w/w 50 50.)
* Patients with Fitzpatrick skin type of 5-6 due to nature of the skin

Laser Treatment Exclusion Criteria

* The presence of acute infection at the proposed treatment site
* Pregnancy or lactation
* Patients with poorly controlled Diabetes mellitus HbA1C \>9% or 75mmol/mol within last 3 months)
* Patients experiencing acute exacerbation of Chronic skin diseases e.g. psoriasis or eczema
* Immunosuppression (HIV, drugs with immunosuppressive effect)
* Use of Roaccutane at any time within the last 6 months
* Autoimmune disorders in active stage (for example: 1. Localised; Type 1 Diabetes Mellitus, Addison's, Grave's and Crohn's Disease, 2. Systemic; Rheumatoid Arthritis, Multiple Sclerosis, Lups and Scleroderma).
* Known history of keloid scarring

Primary outcomes:
measure: Detect the number of senescent cells and the sub-population of fibroblasts 12 months after the last CO2 laser therapy
timeFrame: 18 months
Secondary outcomes:
measure: Vancouver Scar Scale
timeFrame: 18 months
measure: Patient and Observer Scar Assessment Scale (POSAS)
timeFrame: 18 months
measure: Brisbane Burn Scar Impact Profile (BBSIP)
timeFrame: 18 months
measure: Health status
timeFrame: 18 months
measure: Quantify scar colour
timeFrame: 18 months
measure: Quantify scar thickness
timeFrame: 18 months
measure: Quantify scar elasticity
timeFrame: 18 months
measure: Quantify scar volume
timeFrame: 18 months
measure: Novel markers associated with scar formation, wound healing and variables of scar behaviours in response to CO2 laser therapy
timeFrame: 18 months
Other outcomes:
Locations:
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
Study officials:
affiliation: University Hospital Birmingham NHS Foundation Trust
name: Naiem Moiemen, GMC
role: PRINCIPAL_INVESTIGATOR
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