Actinic KeratosisPhase 2NCT04140292
Vitamin D Supplementation as a Neoadjuvant for Photodynamic Therapy of Actinic Keratoses
A Phase 2 study testing Photodynamic therapy (PDT) and Vitamin D3 in people with Actinic Keratosis, run by Case Comprehensive Cancer Center at 1 site in United States.
Trial summary
This study is open to individuals with Actinic Keratoses (skin lesions that have the potential to turn into skin cancer), who are receiving photodynamic therapy (PDT) as part of their clinical care. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Actinic Keratosis
- What is being tested?
- Photodynamic therapy (PDT) and Vitamin D3
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jan 2020to 27 May 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Actinic keratoses in sufficient numbers (>10) to warrant PDT therapy in the clinic
- Able to understand and willing to sign a written informed consent document
- Female subjects must not become pregnant during the study:
- The effects of 5-aminolevulinic acid (LevulanTM) on the human fetus are unknown. For this reason, women of child-bearing potential must agree to use contraception (double barrier method of birth control or abstinence) prior to study entry, and throughout study participation. Should a woman become pregnant or suspect that she is pregnant while she is participating in this study, she should inform the treating physician immediately.
Who cannot join
- Pregnant or nursing.
- At risk for hypercalcemia (renal disease, sarcoidosis, etc.)
- Using topical retinoids, since these can exacerbate the post-PDT erythema reaction.
- Using any topical treatment on their AKs; must stop at least one month prior.
- Currently undergoing treatment for other cancers with medical or radiation therapy.
- Patients with a known hypersensitivity to 5-aminolevulinic acid or any component of the study material.
- Patients with history of a photosensitivity disease, such as porphyria cutanea tarda.
- Currently participating in another clinical trial.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
This study is open to individuals with Actinic Keratoses (skin lesions that have the potential to turn into skin cancer), who are receiving photodynamic therapy (PDT) as part of their clinical care. The purpose of this study is to test and demonstrate that vitamin D pre-treatment can enhance PDT efficacy in the treatment of Actinic Keratoses.
Participants will be asked to take vitamin D supplements prior to their standard of care PDT treatment.
Participation in the research will last about 3-4 months.
Read the detailed description
The primary objective of this study is to determine whether acute supplementation (neoadjuvant Vitamin D3), adjusted according to baseline Vitamin D status, can improve the clinical PDT response relative to participants receiving PDT alone
The secondary objective of this study is to determine whether gene polymorphisms in VDR and CYP27B1 are predictive for the degree of responsiveness to Vitamin D as a neoadjuvant for PDT.
This study is a non-randomized interventional trial, in which the study group will be compared to a baseline cohort of patients from a previous study who received the same regimen of PDT, but without any Vit D. It is anticipated that 30 participants will be involved in this study.
- Conditions
- Actinic Keratosis
- Being tested
- Photodynamic therapy (PDT), Vitamin D3
- Medical subject headings
- Keratosis, Actinic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Photodynamic therapy (PDT)Drug
PDT is a technique that combines a photosensitizing drug and an intense light source to kill tumor cells
Noninvasive fluorescence dosimetry may be performed on up to 6 lesions. Levulan Kerastick will be applied to each lesion and left to incubate for 30 minutes. Blue light (Blu-U device, 20 J/cm2, 33 minutes) will be administered.
Vitamin D3Drug
D3 pills (10,000 IU each) to be taken daily at home, beginning at either day -5 or day -14, as per their assignment
Participants will receive a 5-day or 14-day supplementation of Vitamin D10,000 IU depending on their baseline Vitamin D 25 Hydroxy result
| Study group | Role | What they receive |
|---|---|---|
| Vitamin D3 + Photodynamic therapy (PDT) | Experimental | Patients receive Vitamin D3 10,000 IU daily for 5 or 14 days depending on VitD baseline level. They then undergo Photodynamic therapy (PDT) for treatment of actinic keratosis. Receives: Drug: Photodynamic therapy (PDT); Drug: Vitamin D3 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months
Clinical PDT response as measured by the percent change of AK lesions 3 months after treatment
Baseline vitamin D (calcidiol) level will be taken for each patient.
Measured: 3 months after treatment
Secondary outcomes (4)
Correlation Between Vitamin D Receptor (VDR) Polymorphisms and Percent Reduction in AK
Whether gene polymorphisms in VDR and CYP27B1 are predictive for the degree of responsiveness (as measured by percent reduction in AK) to Vitamin D as a neoadjuvant for PDT.
Measured: 3 months after treatment
Number of Participants Reporting 1 or Higher on the Pain Scale
Pain scale recorded on a 0-to-10 visual/analog scale, with higher scores mean more pain; 0 is no pain, 10 is "the worst pain imaginable". Number of participants receiving treatment that reported a pain level greater than 1.
Measured: During treatment (at the 5 min mark), and again immediately afterwards.
Tolerability as Measured by Participants' Symptom Score Sheets
Participants are asked to recall the symptoms they experienced during the week following PDT. The study physician asks them whether they had experienced each of the following 13 symptoms (YES/NO), and positive (YES) answers were summed to create a Side Effects Score (SES). The maximum and minimum possible values are 13 and 0 respectively, with a higher score correlating to poorer participant outcomes.
The 13 possible side effects were: pain, erythema, scabbing, blistering, erosions, edema, warmth, exfoliation, discharge, hemorrhage, tightness, hyperpigmentation, hypopigmentation.
Measured: 1 week after treatment
Accumulation of Protoporphyrin IX (PpIX) Within AK
Accumulation of protoporphyrin IX (PpIX) within AK
PpIX accumulation in areas of both actinic damage and normal skin will be measured with a fluorescence dosimeter. The level of calcidiol, a clinically accepted marker of vitamin D status, will be measured in each patient to see if supplementation with 10,000 IU of Vitamin D increase the accumulation
Measured: 3 months after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Oct 2019
- Study start13 Jan 2020
- Primary completion24 Nov 2020
- Study completion27 May 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Actinic KeratosisStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Study group will be compared to a baseline cohort of patients from a previous study (IRB 16-1615) who received the same regimen of PDT, but without any Vit D
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Edward V Maytin, MD, PhD, Principal investigator, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04140292
- Sponsor's protocol ID
- CASE5619
- Status last verified
- Jun 2022
- First submitted
- 24 Oct 2019
- Last updated
- 24 Jun 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All IPD that underlie results in publication
Publications
Bullock TA, Negrey J, Hu B, Warren CB, Hasan T, Maytin EV. Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. J Am Acad Dermatol. 2022 Jul;87(1):80-86. doi: 10.1016/j.jaad.2022.02.067. Epub 2022 Mar 18.
PubMed 35314199
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D Supplementation as a Neoadjuvant for Photodynamic Therapy of Actinic Keratoses
- ClinicalTrials.gov ID
- NCT04140292
- Acronym / sponsor ID
- CASE5619
- Conditions
- Actinic Keratosis
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 13 Jan 2020 (actual)
- Primary completion
- 24 Nov 2020 (actual)
- Study completion
- 27 May 2021 (actual)
- First posted
- 25 Oct 2019 (actual)
- Results
- Posted 24 Jun 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is open to individuals with Actinic Keratoses (skin lesions that have the potential to turn into skin cancer), who are receiving photodynamic therapy (PDT) as part of their clinical care. The purpose of this study is to test and demonstrate that vitamin D pre-treatment can enhance PDT efficacy in the treatment of Actinic Keratoses.
Participants will be asked to take vitamin D supplements prior to their standard of care PDT treatment.
Participation in the research will last about 3-4 months.
Detailed description
The primary objective of this study is to determine whether acute supplementation (neoadjuvant Vitamin D3), adjusted according to baseline Vitamin D status, can improve the clinical PDT response relative to participants receiving PDT alone
The secondary objective of this study is to determine whether gene polymorphisms in VDR and CYP27B1 are predictive for the degree of responsiveness to Vitamin D as a neoadjuvant for PDT.
This study is a non-randomized interventional trial, in which the study group will be compared to a baseline cohort of patients from a previous study who received the same regimen of PDT, but without any Vit D. It is anticipated that 30 participants will be involved in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Study group will be compared to a baseline cohort of patients from a previous study (IRB 16-1615) who received the same regimen of PDT, but without any Vit D
| Arm | Type | Receives |
|---|---|---|
| Vitamin D3 + Photodynamic therapy (PDT) | Experimental | Drug: Photodynamic therapy (PDT), Drug: Vitamin D3Patients receive Vitamin D3 10,000 IU daily for 5 or 14 days depending on VitD baseline level. They then undergo Photodynamic therapy (PDT) for treatment of actinic keratosis. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Actinic keratoses in sufficient numbers (>10) to warrant PDT therapy in the clinic
- Able to understand and willing to sign a written informed consent document
- Female subjects must not become pregnant during the study:
Key exclusion criteria (8 listed)
- Pregnant or nursing.
- At risk for hypercalcemia (renal disease, sarcoidosis, etc.)
- Using topical retinoids, since these can exacerbate the post-PDT erythema reaction.
- Using any topical treatment on their AKs; must stop at least one month prior.
- Currently undergoing treatment for other cancers with medical or radiation therapy.
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 |
|---|---|---|
| Photodynamic therapy (PDT)PDT is a technique that combines a photosensitizing drug and an intense light source to kill tumor cells Noninvasive fluorescence dosimetry may be performed on up to 6 lesions. Levulan Kerastick will be applied to each lesion and left to incubate for 30 minutes. Blue light (Blu-U device, 20 J/cm2, 33 minutes) will be administered. | Drug | Vitamin D3 + Photodynamic therapy (PDT) |
| Vitamin D3D3 pills (10,000 IU each) to be taken daily at home, beginning at either day -5 or day -14, as per their assignment Participants will receive a 5-day or 14-day supplementation of Vitamin D10,000 IU depending on their baseline Vitamin D 25 Hydroxy result | Drug | Vitamin D3 + Photodynamic therapy (PDT) |
Primary outcome
Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months
Time frame: 3 months after treatment
Clinical PDT response as measured by the percent change of AK lesions 3 months after treatment Baseline vitamin D (calcidiol) level will be taken for each patient.
4 secondary outcomes
Correlation Between Vitamin D Receptor (VDR) Polymorphisms and Percent Reduction in AK
Time frame: 3 months after treatment
Number of Participants Reporting 1 or Higher on the Pain Scale
Time frame: During treatment (at the 5 min mark), and again immediately afterwards.
Tolerability as Measured by Participants' Symptom Score Sheets
Time frame: 1 week after treatment
Accumulation of Protoporphyrin IX (PpIX) Within AK
Time frame: 3 months after treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35314199Bullock TA, Negrey J, Hu B, Warren CB, Hasan T, Maytin EV. Significant improvement of facial actinic keratoses after blue light photodynamic therapy with oral vitamin D pretreatment: An interventional cohort-controlled trial. J Am Acad Dermatol. 2022 Jul;87(1):80-86. doi: 10.1016/j.jaad.2022.02.067. Epub 2022 Mar 18.
- Individual participant dataSharing planned: Yes. All IPD that underlie results in publication
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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.
Edward V Maytin, MD, PhD principal investigator
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Photodynamic therapy (PDT) and Vitamin D3 in people with Actinic Keratosis, run by Case Comprehensive Cancer Center at 1 site in United States.
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 4 inclusion and 8 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 24 Jun 2022. 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 United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Jun 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months (time frame: 3 months after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04140292, which also lists 1 linked publication.
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 24 Jun 2022.