FS2 Safety and Tolerability Study in Healthy Volunteers
Condition: Cicatrix; Cicatrix, Hypertrophic; Keloid
MeSH terms: Cicatrix; Cicatrix, Hypertrophic
Study type: Interventional
Phase: Phase 1

Summary: 
      Background Scarring typically occurs after trauma, burn injury or surgery. Hypertrophic
      scarring presents as raised, red and itchy lesions which variably respond to various
      treatment modalities, such as corticosteroids, pressure garments, laser therapy, the use of
      silicone sheets and radiotherapy.

      Kynurenine, or "Fibrostop 1" (FS1), and its further breakdown products, such as kynurenic
      acid, or "Fibrostop 2" (FS2), are endogenous products found in many systems and have shown
      potential in reducing scar formation in animal studies.

      The aim of study is to evaluate the safety and tolerability of FS2 cream applied to the skin
      of healthy human subjects.
    

Detailed description: 
      Scarring typically occurs after trauma, burn injury or surgery. Hypertrophic scars (scars
      with excessive amounts of a protein called collagen) and keloids (hypertrophic scars that
      grow beyond the boundaries of the original wound) are types of abnormal scarring that are
      termed "dermal fibroproliferative disorders" - disorders of abnormal growth of fibrous tissue
      in the dermis, a layer in normal skin. These disorders present as raised, red and itchy
      lesions which variably respond to various treatment modalities, such as corticosteroids,
      pressure garments, laser therapy, the use of silicone sheets and radiotherapy. Surgical
      excision of hypertrophic scars or keloids often leads to recurrence resulting in cosmetic
      deformities and contractures.

      In a previous study involving a hypertrophic scar rabbit model, it was found that collagen
      deposition could be reduced by increasing the activity of a molecule called MMP-1 (matrix
      metalloproteinase 1), an enzyme inside body cells. The investigators also know from the
      investigators previous work that a molecule called kynurenine, a breakdown product of
      amino-acids, can reduce collagen deposition and possibly stimulate MMP production.

      Kynurenine is a breakdown product (catabolite) of the essential amino acid tryptophan used in
      the production of niacin - an organic compound and essential human nutrient found in food.
      Kynurenine is made by the enzyme indoleamine 2,3-dioxygenase (IDO) which is found in many
      tissues in response to activation of the immune systen, and also by the enzyme tryptophan
      dioxygenase, which is found in the liver. Kynurenine is further converted to kynurenic acid,
      or "Fibrostop 2" (FS2), carry out many functions in the body, including dilating blood
      vessels during inflammation and regulating the immune response.

      The investigators have hypothesized that improved healing outcomes in the investigators
      rabbit model were due to kynurenine and by-products stimulating MMP, which in turn acted on
      cells (fibroblasts) to reduce collagen production. This hypothesis lead to a study
      investigating the effects of topical 0.5% kynurenine cream treatment on MMP-1 and MMP-3
      expression in fibrotic rabbit ear wound model. The results showed marked improvement in scar
      formation suggesting the possible use of kynurenine as an anti-fibrogenic treatment against
      scarring.

      Toxicity, pharmacodynamic, and pharmacokinetic data has been completed, and the investigators
      institution is now preparing to conduct its first Phase I clinical trial. The investigators
      objective is to evaluate the safety and tolerability of topically applied FS2 in healthy
      human subjects by conducting a double-blinded acute and chronic sensitivity study involving
      patch testing.
    

Intervention name(s): Acute Application of kynurenic acid cream; Chronic application of kynurenic acid cream
Intervention type(s): Drug; Drug
Intervention description(s): Pouches containing 0.00% (placebo), 0.15%, 0.25%, 0.4% and 0.5% of FS2 will be randomly applied to an occlusive, transparent dressing (Tegaderm) and applied to each test area. The pouch order will be random, generated by the www.random.org list generator each application. The study team member applying the cream will randomly choose the application sites of different concentrations of the FS2 creams and mark the corresponding cream code name on a separate sheet. This study member will not be evaluating the results and the evaluating study member will be blinded to the randomization. Patients will be evaluated at 24 hours post application for skin reactions and adverse reactions by a blinded observer recorded. Before and after photographs will be taken.; Volunteers will be educated how to apply a pouch of cream to an occlusive, transparent dressing (Tegaderm) and place it on the test site every 24 hours for 30 days. The date and time of first application will be recorded. Baseline urine and serum measurements of drug concentration (presumed absent), as well as complete blood count, liver enzymes, blood urea nitrogen, and creatinine will be taken on Day 0 (the initial enrollment of each part). The volunteers will be seen in follow-up at day 1, day 5, day 15, and day 30
Other intervention name(s): Fibrostop 2 (FS2); Fibrostop 2 (FS2)
Intervention MeSH terms: Kynurenic Acid
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment