- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04223570
Portable Measurement of Protoporphyrin IX in the Skin
August 25, 2023 updated by: Michael S. Chapman, Dartmouth-Hitchcock Medical Center
Photodynamic therapy (PDT) is increasingly used to treat superficial skin lesions, such as actinic keratosis (AK) and non-melanoma skin cancers, and has been demonstrated to be an effective and safe alternative to surgery.
It is performed by applying a photosensitizing pro-drug, amino -levulinic acid (ALA) and then allowing the conversion to the metabolite Protoporphyrin IX (PpIX).
While attempts to measure the concentration of this drug in the skin have been performed before, there remains limited research on an individuals' baseline level of PpIX which could lead to the customization of PDT.
With the development of a new handheld, smart phone-associated device to measure red fluoresce intensity of PpIX, this measurement is now feasible.
This is an observational single center quantitative study in which the investigators will take measurements of red fluoresce intensity of PpIX at various locations.
This will then be correlated with the individuals age, oral temperature, diet, and skin type.
The investigators hypothesize that the levels of PpIX will depend on all of these factors, including anatomical location.
All data will be collected into the data collection form and then analyzed.
The investigators will assess for how anatomical location, skin pigmentation, oral temperature, and other factors influence PpIX levels.
Fitzpatrick skin type will be assessed by the provider to assess skin pigmentation.
All of these factors will be correlated to the PpIX levels in 5 anatomical locations (forehead, cheeks, forearms, hands, and bald scalp where applicable) to determine which factors most greatly influence the red fluoresce intensity of PpIX.
Study Overview
Status
Enrolling by invitation
Conditions
Intervention / Treatment
Detailed Description
Photodynamic Therapy (PDT) has gained popularity as an effective, non-scarring treatment for thin, non-hyperkeratotic actinic keratoses (AKs).
Similar to the topical agents 5-fluorouracil and imiquimod, PDT is particularly useful when utilized as a field-directed therapy for the treatment of areas with multiple AKs and extensive sun damage.
PDT consists of two steps: 1) the topical application of a photosensitizer agent aminolevulinic acid (ALA), which is preferentially converted to the photosensitive protoporphyrin IX (PpIX) in precancerous and neoplastic cells, and 2) controlled exposure to a visible wavelength light source.
Current methodologies utilize a "one-size-fits-all" approach with regard to duration of incubation with photosensitizing agents and illumination.
Moreover, patients frequently experience pain after long PDT prodrug incubation.
Better characterization of photosensitization in PDT can help tailor incubation and overall treatment time to minimize treatment duration and discomfort while maximizing clearance of the target lesions.
The direct measurement of PpIX is a promising, yet rarely performed test that may help determine the appropriate PDT treatment time, the need for re-treatment or adjuvant therapy, and potential efficacy of treatment.
Point-probe measurements have shown extreme heterogeneity between PpIX levels in different patients and among different lesions in the same patient.
However, these point-probe measurements are unable to account for the variance in PpIX production in different parts of the skin because of their relatively limited field of view.
The recent development of a low-cost, smart phone-based, wide-field fluorescence dosimetry imaging system to map PpIX levels onto a 2D image allows for handheld, real-time analysis of PpIX levels in human skin.
Initial unpublished clinical results have shown its utility in human subjects.
However, a more extensive characterization of the factors that influence baseline in PpIX has yet to be performed.
This study intends to elaborate these inter-and intra-individual variances, including analysis of changes in PpIX concentrations based on anatomical location, age, diet, temperature, pigmentation, and previous skin damage.
Study Type
Observational
Enrollment (Estimated)
218
Phase
- Early Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Keegan O'Hern, MD
- Phone Number: 6036505000
- Email: keegan.j.o'hern.med@dartmouth.edu
Study Contact Backup
- Name: Debra Rodgers
- Email: debra.j.rodgers@hitchcock.org
Study Locations
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New Hampshire
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Lebanon, New Hampshire, United States, 03766
- Dartmouth-Hitchcock Medical Center Heater Road Clinic
-
Contact:
- Debra Rodgers
- Email: debra.j.rodgers@hitchcock.org
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Contact:
- Michael S Chapman, MD MBA
- Phone Number: 603-650-3100
- Email: michael.shane.chapman@hitchcock.org
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years to 73 years (Adult, Older Adult)
Accepts Healthy Volunteers
Yes
Sampling Method
Probability Sample
Study Population
Patient subjects will be recruited at the DHMC outpatient dermatology clinic.
Patients presenting for their routine sessions or regularly scheduled follow-up dermatology appointments will be provided information about the study.
Employees at this location will also have the opportunity to participate.
Description
Inclusion Criteria:
- All patients and staff appearing at the Dartmouth-Hitchcock Medical Center Heater Road Dermatology Clinic who are aged 18 years and older
Exclusion Criteria:
- Pregnant women
- Women who are breast-feeding
- Adults unable to consent
- Individuals who are not yet adults
- Prisoners.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Active Comparator: Ameluz (amino-levulinic acid topical gel) Only
Ameluz is a topical gel approved for use in photodynamic therapy for treatment of actinic keratoses, among other skin conditions.
It is being applied to all participants in this study to measure the levels of PpIX in different areas of skin as detailed in study description.
This arm includes those participants who have not been prescribed photodynamic therapy and thus they will not receive any light treatment during this study.
|
Ameluz is a topical gel approved for use in photodynamic therapy for treatment of actinic keratoses.
Other Names:
This is a portable device that uses a camera to non-invasively and efficiently measure the level of protoporphyrin IX in various areas skin.
This camera will be used in all participants to measure the level of protoporphyrin IX in various areas of skin as detailed in the study description.
|
Active Comparator: Ameluz and Light Therapy
Ameluz is a topical gel approved for use in photodynamic therapy for treatment of actinic keratoses, among other skin conditions.
It is being applied to all participants in this study to measure the levels of PpIX in different areas of skin as detailed in study description.
For patients who have been prescribed photodynamic therapy, the investigators will perform one additional round of measurements of Protoporphyrin IX using our camera device, in addition to the other secondary outcomes including skin temperature.
|
Ameluz is a topical gel approved for use in photodynamic therapy for treatment of actinic keratoses.
Other Names:
This is a portable device that uses a camera to non-invasively and efficiently measure the level of protoporphyrin IX in various areas skin.
This camera will be used in all participants to measure the level of protoporphyrin IX in various areas of skin as detailed in the study description.
This blue light is FDA approved to work with the Ameluz gel as part of photodynamic therapy and works with the photosensitizing Ameluz gel to form reactive oxygen species that specifically target precancerous lesions, such as actinic keratoses, without damaging normal, non-cancerous skin.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in Protoporphyrin IX levels on the skin
Time Frame: At baseline
|
Measure change in protoporphyrin IX levels in the skin of the forehead, malar cheek, dorsal hand, and dorsal forearm patients, as well as the bald scalp in male patients
|
At baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Effect of oral temperature on change in protoporphyrin IX levels at baseline and at serial time points after Ameluz application (the intervention)
Time Frame: At baseline
|
Measure oral in temperature and compare it to protoporphyrin levels.
|
At baseline
|
Effect of age on change in protoporphyrin IX levels at baseline and at serial time points after Ameluz application (the intervention)
Time Frame: At baseline
|
Determine the relationship of participant age with change in protoporphyrin IX levels
|
At baseline
|
Effect of Fitzpatrick skin type (skin pigmentation) on change in protoporphyrin IX levels
Time Frame: At baseline
|
Determine the relationship of participant fitzpatrick skin type (skin pigmentation) with change in protoporphyrin IX levels
|
At baseline
|
Effect of diet on change in protoporphyrin IX levels
Time Frame: At baseline
|
Determine the relationship of participant diet with change in protoporphyrin IX levels
|
At baseline
|
Effect of history of skin cancer on change in protoporphyrin IX levels
Time Frame: At baseline
|
Determine the relationship of participant history of skin cancer with change in protoporphyrin IX levels
|
At baseline
|
Effect of sex on change in protoporphyrin IX levels
Time Frame: At baseline
|
Determine the relationship of participant sex with change in protoporphyrin IX levels
|
At baseline
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Michael S Chapman, MD, MBA, Dartmouth-Hitchcock Medical Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Landes R, Illanes A, Goeppner D, Gollnick H, Friebe M. A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy. PLoS One. 2018 Aug 31;13(8):e0202349. doi: 10.1371/journal.pone.0202349. eCollection 2018.
- Anand S, Ortel BJ, Pereira SP, Hasan T, Maytin EV. Biomodulatory approaches to photodynamic therapy for solid tumors. Cancer Lett. 2012 Dec 29;326(1):8-16. doi: 10.1016/j.canlet.2012.07.026. Epub 2012 Jul 25.
- Tyrrell JS, Morton C, Campbell SM, Curnow A. Comparison of protoporphyrin IX accumulation and destruction during methylaminolevulinate photodynamic therapy of skin tumours located at acral and nonacral sites. Br J Dermatol. 2011 Jun;164(6):1362-8. doi: 10.1111/j.1365-2133.2011.10265.x. Epub 2011 May 13.
- Kanick SC, Davis SC, Zhao Y, Hasan T, Maytin EV, Pogue BW, Chapman MS. Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis. J Biomed Opt. 2014;19(7):75002. doi: 10.1117/1.JBO.19.7.075002.
- Nissen CV, Heerfordt IM, Wiegell SR, Mikkelsen CS, Wulf HC. Increased protoporphyrin IX accumulation does not improve the effect of photodynamic therapy for actinic keratosis: a randomized controlled trial. Br J Dermatol. 2017 May;176(5):1241-1246. doi: 10.1111/bjd.15098. Epub 2017 Mar 8.
- Kanick SC, Davis SC, Zhao Y, Sheehan KL, Hasan T, Maytin EV, Pogue BW, Chapman MS. Pre-treatment protoporphyrin IX concentration in actinic keratosis lesions may be a predictive biomarker of response to aminolevulinic-acid based photodynamic therapy. Photodiagnosis Photodyn Ther. 2015 Dec;12(4):561-6. doi: 10.1016/j.pdpdt.2015.10.006. Epub 2015 Oct 22.
- Nissen CV, Philipsen PA, Wulf HC. Protoporphyrin IX formation after topical application of methyl aminolaevulinate and BF-200 aminolaevulinic acid declines with age. Br J Dermatol. 2015 Sep;173(3):760-6. doi: 10.1111/bjd.13923. Epub 2015 Aug 20.
- Zhao B, He YY. Recent advances in the prevention and treatment of skin cancer using photodynamic therapy. Expert Rev Anticancer Ther. 2010 Nov;10(11):1797-809. doi: 10.1586/era.10.154.
- Alberto J. Ruiz, Ethan P. M. LaRochelle, M. Shane Chapman, Tayyaba Hasan, Brian Pogue. Smartphone-based fluorescence imager for PpIX-based PDT treatment planning: System design and initial results. In: Vol 10860. ; 2019. https://doi.org/10.1117/12.2510403.
- Rollakanti KR, Kanick SC, Davis SC, Pogue BW, Maytin EV. Techniques for fluorescence detection of protoporphyrin IX in skin cancers associated with photodynamic therapy. Photonics Lasers Med. 2013 Nov 1;2(4):287-303. doi: 10.1515/plm-2013-0030.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 1, 2022
Primary Completion (Estimated)
March 30, 2024
Study Completion (Estimated)
March 30, 2024
Study Registration Dates
First Submitted
December 24, 2019
First Submitted That Met QC Criteria
January 8, 2020
First Posted (Actual)
January 10, 2020
Study Record Updates
Last Update Posted (Actual)
August 29, 2023
Last Update Submitted That Met QC Criteria
August 25, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- D19167
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
YES
IPD Plan Description
All of the individual participant data collected during the trial, after being de-identified
IPD Sharing Time Frame
Immediately following publication.
No end date.
IPD Sharing Access Criteria
Anyone who wishes to access these data.
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- ANALYTIC_CODE
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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