Actinic Keratosis
Conditions
Brief 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. 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.
Interventions
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.
DRUGVitamin D3
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
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention 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
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Correlation Between Vitamin D Receptor (VDR) Polymorphisms and Percent Reduction in AK | 3 months after treatment | 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. |
| Number of Participants Reporting 1 or Higher on the Pain Scale | During treatment (at the 5 min mark), and again immediately afterwards. | 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. |
| Tolerability as Measured by Participants' Symptom Score Sheets | 1 week after treatment | 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. |
| Accumulation of Protoporphyrin IX (PpIX) Within AK | 3 months after treatment | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3 + Photodynamic Therapy (PDT) 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.
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.
Vitamin D3: 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 | 29 |
| Photodynamic Therapy (PDT) Data for the participants in this arm are from a previous basic science study that looked at Vit D level that got standard of care PDT. These participants were used as a control group. | 26 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Restriction on outpatient visits due to COVID-19. | 4 | 16 |
Baseline characteristics
| Characteristic | Vitamin D3 + Photodynamic Therapy (PDT) | Photodynamic Therapy (PDT) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 17 Participants | 13 Participants | 30 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 13 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 29 Participants | 26 Participants | 55 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 29 Participants | 26 Participants | 55 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Male | 27 Participants | 23 Participants | 50 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: 3 months after treatment
Population: Participants who received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 + Photodynamic Therapy (PDT) | Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months | 59.1 Percent change of AK lesions | Standard Deviation 15.9 |
| Photodynamic Therapy (PDT) | Clinical PDT Response as Measured by Percent Change in AK Lesions From Baseline to 3 Months | 72.5 Percent change of AK lesions | Standard Deviation 13.6 |
Secondary
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
Time frame: 3 months after treatment
Population: Unable to obtain any information about the PpIX accumulation levels because fluorescence imaging dosimeter broke down and it was unable to be replaced.
Secondary
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.
Time frame: 3 months after treatment
Population: Unable to obtain any information about the PpIX accumulation levels because fluorescence imaging dosimeter broke down and it was unable to be replaced.
Secondary
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.
Time frame: During treatment (at the 5 min mark), and again immediately afterwards.
Population: Participants that received treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vitamin D3 + Photodynamic Therapy (PDT) | Number of Participants Reporting 1 or Higher on the Pain Scale | 0 Participants |
| Photodynamic Therapy (PDT) | Number of Participants Reporting 1 or Higher on the Pain Scale | 0 Participants |
Secondary
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.
Time frame: 1 week after treatment
Population: Participants who received treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 + Photodynamic Therapy (PDT) | Tolerability as Measured by Participants' Symptom Score Sheets | 3.7 score on a scale | Standard Deviation 2.2 |
| Photodynamic Therapy (PDT) | Tolerability as Measured by Participants' Symptom Score Sheets | 3.7 score on a scale | Standard Deviation 1.9 |