Normal SkinPhase 4NCT04221126
TMFI Enhances Skin Surface and Epidermal PpIX Fluorescence
A Phase 4 study testing TMFI, ALA cream and ALA gel in people with Normal Skin, run by Merete Haedersdal at 1 site in Denmark.
Trial summary
This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Normal Skin
- What is being tested?
- TMFI, ALA cream and ALA gel
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteDenmark
- Study dates
- 29 Apr 2019to 9 Dec 2019
- Phase
- Phase 4
- 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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- No previous PDT or laser treatment within the past 6 months in the study areas
- Pregnant or lactating women
- Participants with known allergy to 5-ALA, lidocaine or any excipients to components in the vehicles
- Considered unable to follow the study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Thermo-mechanical Fractional Injury Enhances Skin Surface- and Epidermal- Protoporphyrin IX Fluorescence: Comparison of 5-aminolevulinic Acid in Cream and Gel Vehicles
This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle.
Read the detailed description
Topical photodynamic therapy (PDT) is a well-established treatment for dermatological pre-malignant actinic keratoses and Morbus Bowen as well as selected cases of basal cell carcinomas. PDT is exceedingly well suited for treatment of larger skin areas and provide excellent cosmetic results. PDT is based on the photosensitizing drug 5-aminolevulinic acid (5-ALA) that is metabolized into the light-sensitive Protoporphyrin IX, and activated in the skin by light in the visible spectrum. When skin incubated with 5-ALA subsequently is exposed to light, photoactivated PpIX catalyzes a photochemical reaction, which leads to cell apoptosis of the dysplastic or neoplastic tissue. The amount of PpIX fluorescence in the skin is estimated by PpIX fluorescence measurements on skin surface by fluorescence photographs and in the skin depth with fluorescence microscopy. Previous studies have suggested an association of the amount of PpIX in the skin and the clinical outcome of PDT.
The highly lipophilic nature of the stratum corneum (SC) provides the main barrier for influx of drugs and environmental chemicals into the body (6). SC is the greatest impediment for uptake of 5-ALA and the formation of PpIX can be increased by modifying the SC. Pretreatment of the skin facilitates local uptake of photosensitizing agents and is therefore recommended to obtain optimal outcomes in PDT. Recently, different energy-based devices have been introduced for PDT pretreatment to disrupt the SC barrier and effectively increase PpIX accumulation. However, current light-based treatments, such as ablative and non-ablative lasers, are painful to patients and induce thermal damage that result in oozing, crusting or peeling of the skin.
To increase cutaneous absorption with minimal damage to the skin, thermo-mechanical fractional intervention (TMFI) has been introduced as a new technology. TMFI rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates the epidermis and superficial dermis and create micropores with no coagulative damage of surrounding tissue. The amount of thermal energy delivered can be adjusted by pulse duration and by the protrusion depth of the tip that sets the thermal matching between the tip and the skin. TMFI has in one study shown to increase uptake of hydrophilic drugs compared with no skin pretreatment. As TMI dehydrates the epidermis, hydrophilic drugs dissolved in a low viscosity liquid-based vehicle may be more readily distributed within the skin compared to drugs dissolved in a high viscosity vehicle.
The investigators hypothesize that i) TMFI increases 5-ALA induced PpIX accumulation compared with no pretreatment and that ii) TMFI + 5-ALA in a low viscosity vehicle formulation enhances PpIX skin biodistribution compared with 5-ALA in a high viscosity vehicle formulation.
Potentially, TMFI pretreatment could improve PpIX biodistribution and reduce photosensitizer incubation time to obtain sufficient PpIX accumulation. This could significantly benefit thousands of patients who each year undergo PDT for dysplastic skin lesions.
- Conditions
- Normal Skin
- Being tested
- TMFI, ALA cream, ALA gel
- Keywords
- protoporphyrin ix, 5-aminolevulinic acid, thermo-mechanical intervention, normal skin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TMFIDevice
Also called Thermo-mechanical fractional injury
Tixel rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates he epidermis and superficial dermis and creates micropores with no coagulative damage of surronding tissue.
ALA creamDrug
Also called 5-aminolevulinic acid compounded in a cream
ALA compounded in a cream
ALA gelDrug
Also called 5-aminolevulinic acid compounded in a gel
ALA compounded in a gel
| Study group | Role | What they receive |
|---|---|---|
| TMFI +cream | Experimental | TMFI + ALA cream Receives: Device: TMFI; Drug: ALA cream |
| TMFI + gel | Experimental | TMFI + ALA gel Receives: Device: TMFI; Drug: ALA gel |
| ALA creAM | Active comparator | ALA cream Receives: Drug: ALA cream |
| ALA GEL | Active comparator | ALA gel Receives: Drug: ALA gel |
| Control | No intervention | Untreated control with no intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in PpIX fluorescence at skin surface following TMFI and topical 5-ALA in gel and cream vehicle
Levels of PpIX uptake at the skin surface quantitatively from PpIX imaging.
Measured: Baseline and in 30-minute intervals until 3 hours
PpIX fluorescence biodistribution inside skin
Levels of PpIX uptake inside predefined skin regions: Epidermis, superficial dermis, mid dermis and deep dermis evaluated on fluorescence microscopy images. Biopsies used for fluorescence microscopy was sampled after 3 hours.
Measured: 3 hours
Secondary outcomes (6)
Histological skin interactions after TMFI
Biopsies were stained with haematoxylin and eosin (HE) for light microscopy for histopathology analysis of TMFI effect on the skin. Depth and width of the TMFI effect on the skin was measured.
Measured: 3 hours
Severity of local skin reactions
Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters:
Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.
Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.
Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.
Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.
Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.
Measured: 5 minutes after TMFI pretreatment
Severity of local skin reactions
Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters:
Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.
Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.
Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.
Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.
Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.
Measured: 3 hours after TMFI pretreatment
Severity of local skin reactions
Local skin reaction (LSR)-grading scale. Evaluation of redness, scaling, edema, pustules, and erosion on a 5-point categorial scale of severity. Scores are 0, 1, 2, 3, and 4, for individual parameters:
Redness: None, slightly pink <50%, pink or light red >50%, red restricted to treatment area, and red extending outside treatment area.
Scaling: None, isolated scale, scaling <50%, scaling >50%, scaling extending outside treatment area.
Edema: None, slight specific edema, palpable edema beyond individual lesions, confluent and/or visible edema, and marked swelling extending outside treatment area.
Pustules: None, vesicles only, transudate or pustules <50%, transudate or pustules >50%, and transudate or pustules extending outside treatment area.
Erosion: None, lesion specific erosion, erosion extending beyond individual lesion, erosion >50%, and black eschar or ulceration.
Measured: 14 days after TMFI pretreatment
Presence of perceived pain during treatment
VAS Visual analogue scale for perceived pain. Scores are 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10, ranging from none to very severe. Higher is worse, and lower scores for treatment modalities are desirable.
Measured: During the actual TMFI pretreatment, estimated 1-2 minute per participant
Safety including wounding, scarring, hyper and hypo pigmentation
Safety concerning side-effects evaluated on a 5-point categorial scale for hyper- and hypopigmentation, erosions, and scarring. Scores are 0, 1, 2, 3, and 4, for none, mild, moderate, severe, and very severe. A lower score is desirable.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2020
- Study start29 Apr 2019
- Primary completion8 Aug 2019
- Study completion9 Dec 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Normal SkinStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Merete Haedersdal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Merete Haedersdal, Bispebjerg Hospital
- Investigators
- Merete Hædersdal, DMSc, Study director, Bispebjerg Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04221126
- Sponsor's protocol ID
- 2018-004397-96
- Other IDs
- 2018
- Status last verified
- Jan 2020
- First submitted
- 27 Dec 2019
- Last updated
- 9 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thermo-mechanical Fractional Injury Enhances Skin Surface- and Epidermal- Protoporphyrin IX Fluorescence: Comparison of 5-aminolevulinic Acid in Cream and Gel Vehicles
- ClinicalTrials.gov ID
- NCT04221126
- Acronym / sponsor ID
- 2018-004397-96
- Conditions
- Normal Skin
- Keywords
- protoporphyrin ix, 5-aminolevulinic acid, thermo-mechanical intervention, normal skin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Merete HaedersdalUniversity, hospital or other
- Study start
- 29 Apr 2019 (actual)
- Primary completion
- 8 Aug 2019 (actual)
- Study completion
- 9 Dec 2019 (actual)
- First posted
- 9 Jan 2020 (actual)
- 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.
This study investigates a relatively new device TMFI and incubation of ALA in a cream-vehicle and a gel-vehicle.
Detailed description
Topical photodynamic therapy (PDT) is a well-established treatment for dermatological pre-malignant actinic keratoses and Morbus Bowen as well as selected cases of basal cell carcinomas. PDT is exceedingly well suited for treatment of larger skin areas and provide excellent cosmetic results. PDT is based on the photosensitizing drug 5-aminolevulinic acid (5-ALA) that is metabolized into the light-sensitive Protoporphyrin IX, and activated in the skin by light in the visible spectrum. When skin incubated with 5-ALA subsequently is exposed to light, photoactivated PpIX catalyzes a photochemical reaction, which leads to cell apoptosis of the dysplastic or neoplastic tissue. The amount of PpIX fluorescence in the skin is estimated by PpIX fluorescence measurements on skin surface by fluorescence photographs and in the skin depth with fluorescence microscopy. Previous studies have suggested an association of the amount of PpIX in the skin and the clinical outcome of PDT.
The highly lipophilic nature of the stratum corneum (SC) provides the main barrier for influx of drugs and environmental chemicals into the body (6). SC is the greatest impediment for uptake of 5-ALA and the formation of PpIX can be increased by modifying the SC. Pretreatment of the skin facilitates local uptake of photosensitizing agents and is therefore recommended to obtain optimal outcomes in PDT. Recently, different energy-based devices have been introduced for PDT pretreatment to disrupt the SC barrier and effectively increase PpIX accumulation. However, current light-based treatments, such as ablative and non-ablative lasers, are painful to patients and induce thermal damage that result in oozing, crusting or peeling of the skin.
To increase cutaneous absorption with minimal damage to the skin, thermo-mechanical fractional intervention (TMFI) has been introduced as a new technology. TMFI rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates the epidermis and superficial dermis and create micropores with no coagulative damage of surrounding tissue. The amount of thermal energy delivered can be adjusted by pulse duration and by the protrusion depth of the tip that sets the thermal matching between the tip and the skin. TMFI has in one study shown to increase uptake of hydrophilic drugs compared with no skin pretreatment. As TMI dehydrates the epidermis, hydrophilic drugs dissolved in a low viscosity liquid-based vehicle may be more readily distributed within the skin compared to drugs dissolved in a high viscosity vehicle.
The investigators hypothesize that i) TMFI increases 5-ALA induced PpIX accumulation compared with no pretreatment and that ii) TMFI + 5-ALA in a low viscosity vehicle formulation enhances PpIX skin biodistribution compared with 5-ALA in a high viscosity vehicle formulation.
Potentially, TMFI pretreatment could improve PpIX biodistribution and reduce photosensitizer incubation time to obtain sufficient PpIX accumulation. This could significantly benefit thousands of patients who each year undergo PDT for dysplastic skin lesions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| TMFI +cream | Experimental | Device: TMFI, Drug: ALA creamTMFI + ALA cream |
| TMFI + gel | Experimental | Device: TMFI, Drug: ALA gelTMFI + ALA gel |
| ALA creAM | Active comparator | Drug: ALA creamALA cream |
| ALA GEL | Active comparator | Drug: ALA gelALA gel |
| Control | No intervention | –Untreated control with no intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (4 listed)
- No previous PDT or laser treatment within the past 6 months in the study areas
- Pregnant or lactating women
- Participants with known allergy to 5-ALA, lidocaine or any excipients to components in the vehicles
- Considered unable to follow the study protocol
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 |
|---|---|---|
| TMFIAlso: Thermo-mechanical fractional injuryTixel rapidly transfer thermal energy by a metallic pyramid tip that enable skin contact through integrated pulsed movements. The rapid heating dehydrates he epidermis and superficial dermis and creates micropores with no coagulative damage of surronding tissue. | Device | TMFI + gel, TMFI +cream |
| ALA creamAlso: 5-aminolevulinic acid compounded in a creamALA compounded in a cream | Drug | ALA creAM, TMFI +cream |
| ALA gelAlso: 5-aminolevulinic acid compounded in a gelALA compounded in a gel | Drug | ALA GEL, TMFI + gel |
Primary outcome
Change in PpIX fluorescence at skin surface following TMFI and topical 5-ALA in gel and cream vehicle
Time frame: Baseline and in 30-minute intervals until 3 hours
Levels of PpIX uptake at the skin surface quantitatively from PpIX imaging.
PpIX fluorescence biodistribution inside skin
Time frame: 3 hours
Levels of PpIX uptake inside predefined skin regions: Epidermis, superficial dermis, mid dermis and deep dermis evaluated on fluorescence microscopy images. Biopsies used for fluorescence microscopy was sampled after 3 hours.
6 secondary outcomes
Histological skin interactions after TMFI
Time frame: 3 hours
Severity of local skin reactions
Time frame: 5 minutes after TMFI pretreatment
Severity of local skin reactions
Time frame: 3 hours after TMFI pretreatment
Severity of local skin reactions
Time frame: 14 days after TMFI pretreatment
Presence of perceived pain during treatment
Time frame: During the actual TMFI pretreatment, estimated 1-2 minute per participant
Safety including wounding, scarring, hyper and hypo pigmentation
Time frame: 14 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 9 Jan 2020.
- Individual participant dataSharing planned: No
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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.
Merete Hædersdal, DMSc study director
Bispebjerg Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing TMFI, ALA cream and ALA gel in people with Normal Skin, run by Merete Haedersdal at 1 site in Denmark.
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 0 inclusion and 4 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 9 Jan 2020. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Change in PpIX fluorescence at skin surface following TMFI and topical 5-ALA in gel and cream vehicle (time frame: Baseline and in 30-minute intervals until 3 hours). The study lists 2 primary outcomes in all. 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 9 Jan 2020.