CicatrixPhase 1NCT02340325
FS2 Safety and Tolerability Study in Healthy Volunteers
A Phase 1 study testing Acute Application of kynurenic acid cream and Chronic application of kynurenic acid cream in people with Cicatrix and Cicatrix, Hypertrophic, run by British Columbia Professional Firefighters' Burn and Wound Healing Laboratory at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cicatrix, Cicatrix, Hypertrophic, Keloid
- What is being tested?
- Acute Application of kynurenic acid cream and Chronic application of kynurenic acid cream
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteCanada
- Study dates
- May 2015to Jan 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy males or females between the ages of 18 and 65
- English as a primary language, or English as a second language (ESL) but completely fluent and do not require a translator
Who cannot join
- Pregnant, or attempting to become pregnant (NB: Pregnancy tests will be administered at the screening and baseline visit.)
- History of chronic skin conditions (e.g: eczema, psoriasis, etc.)
- Use of oral anti-histamines in the past month
- Use of systemic steroids in the past month
- Chronic use of NSAIDs or other anti-inflammatory medications
- Known immunosuppression or immunosuppressive illness
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- Known sensitivity to parabens
- Known allergy to the the bandage adhesive
- English as a second language (ESL) and require a translator.
Trial locations and contacts
1 site in 1 country.
Canada1 site
BCPFF Burn & Wound Healing Lab
Vancouver, British Columbia, V5Z1M9
About this study
Official title: The Safety of Topically Delivered FS2 in Humans. Phase 1 Clinical Trial
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.
Read the 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.
- Conditions
- Cicatrix, Cicatrix, Hypertrophic, Keloid
- Being tested
- Acute Application of kynurenic acid cream, Chronic application of kynurenic acid cream
- Medical subject headings
- Cicatrix, Cicatrix, Hypertrophic, Keloid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Application of kynurenic acid creamDrug
Also called Fibrostop 2 (FS2)
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.
Chronic application of kynurenic acid creamDrug
Also called Fibrostop 2 (FS2)
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
| Study group | Role | What they receive |
|---|---|---|
| Acute Sensitivity Test to FS2 cream | Other | Twenty (20) healthy volunteers will be assigned volunteer numbers and will have a testing areas identified by permanent marker on their backs. 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 once for 24 hours. The pouch order will be random, generated by the www.random.org list generator each application. 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. Receives: Drug: Acute Application of kynurenic acid cream |
| Chronic Sensitivity Test to FS2 cream | Other | Twenty (20) randomized healthy volunteers will be assigned numbers and will have a single testing area identified by permanent marker on either shoulder or upper back. 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. Receives: Drug: Chronic application of kynurenic acid cream |
What is being measured
The primary outcome is the main question the study is designed to answer.
Acute skin irritation or local reaction
After application of various concentrations of the active substance, patients will be evaluated at 24 hours post application for skin reactions and adverse reactions by a blinded observer
Measured: 24 hours
Secondary outcomes (2)
Chronic skin irritation or local reaction
After application of various concentrations of the active substance, patients will be evaluated post application for skin reactions and adverse reactions by a blinded observer. The volunteers will be seen in follow-up at day 1, day 5, day 15, and day 30
Measured: 1 month
Chronic exposure serum drug levels
After application of various concentrations of the active substance, patients will have blood taken and analyzed using high performance liquid chromatography. The volunteers will be seen in follow-up at day 1, day 5, day 15, and day 30
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2015 (estimated)
- Study startMay 2015
- Primary completionJan 2016
- Study completionJan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CicatrixStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- British Columbia Professional Firefighters' Burn and Wound Healing Laboratory
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anthony Papp, British Columbia Professional Firefighters' Burn and Wound Healing Laboratory
- Investigators
- Anthony Papp, MD, Principal investigator, BC Professional Fire Fighters' Burn and Wound Healing Laboratory
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02340325
- Sponsor's protocol ID
- H14-00143
- Status last verified
- Feb 2016
- First submitted
- 1 Dec 2014
- Last updated
- 2 Feb 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Safety of Topically Delivered FS2 in Humans. Phase 1 Clinical Trial
- ClinicalTrials.gov ID
- NCT02340325
- Acronym / sponsor ID
- H14-00143
- Conditions
- Cicatrix, Cicatrix, Hypertrophic, Keloid
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- British Columbia Professional Firefighters' Burn and Wound Healing LaboratoryUniversity, hospital or other
- Study start
- May 2015
- Primary completion
- Jan 2016 (actual)
- Study completion
- Jan 2016 (actual)
- First posted
- 16 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute Sensitivity Test to FS2 cream | Other | Drug: Acute Application of kynurenic acid creamTwenty (20) healthy volunteers will be assigned volunteer numbers and will have a testing areas identified by permanent marker on their backs. 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 once for 24 hours. The pouch order will be random, generated by the www.random.org list generator each application. 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. |
| Chronic Sensitivity Test to FS2 cream | Other | Drug: Chronic application of kynurenic acid creamTwenty (20) randomized healthy volunteers will be assigned numbers and will have a single testing area identified by permanent marker on either shoulder or upper back. 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy males or females between the ages of 18 and 65
- English as a primary language, or English as a second language (ESL) but completely fluent and do not require a translator
Key exclusion criteria (9 listed)
- Pregnant, or attempting to become pregnant (NB: Pregnancy tests will be administered at the screening and baseline visit.)
- History of chronic skin conditions (e.g: eczema, psoriasis, etc.)
- Use of oral anti-histamines in the past month
- Use of systemic steroids in the past month
- Chronic use of NSAIDs or other anti-inflammatory medications
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute Application of kynurenic acid creamAlso: Fibrostop 2 (FS2)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. | Drug | Acute Sensitivity Test to FS2 cream |
| Chronic application of kynurenic acid creamAlso: Fibrostop 2 (FS2)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 | Drug | Chronic Sensitivity Test to FS2 cream |
Primary outcome
Acute skin irritation or local reaction
Time frame: 24 hours
After application of various concentrations of the active substance, patients will be evaluated at 24 hours post application for skin reactions and adverse reactions by a blinded observer
2 secondary outcomes
Chronic skin irritation or local reaction
Time frame: 1 month
Chronic exposure serum drug levels
Time frame: 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Feb 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anthony Papp, MD principal investigator
BC Professional Fire Fighters' Burn and Wound Healing Laboratory
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Acute Application of kynurenic acid cream and Chronic application of kynurenic acid cream in people with Cicatrix and Cicatrix, Hypertrophic, run by British Columbia Professional Firefighters' Burn and Wound Healing Laboratory at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acute skin irritation or local reaction (time frame: 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2016.