Actinic Porokeratosis
Conditions
Brief summary
This study will analyze the effects of topical lovastatin/cholesterol vs topical lovastatin alone in patients with disseminated superficial actinic porokeratosis. Patients will be divided into two groups, topical lovastatin/cholesterol and topical lovastatin alone. Patients will apply topical treatment twice daily to lesions over the course of 12 weeks. Follow up will occur in the virtual setting and photographs will be used to document progress.
Detailed description
The purpose of this study is to evaluate the effectiveness of cholesterol/lovastatin versus lovastatin alone to treat porokeratosis. Our working hypothesis is that both topical cholesterol/lovastatin and lovastatin alone are helpful in treating patients with disseminated superficial actinic porokeratosis (DSAP). Potential subjects will be approached by their care team member to be made aware of the study at MUSC Dermatology clinics. Subsequently, members of the study team will approach their own patients to ask for participation in this study. Pertinent project information, risks, and time commitment will be relayed to subjects. If subjects show interest in participating, they will be given consent forms to either sign or bring home for consideration. If the patient is eligible for the study, he or she will be randomly assigned to one of two groups. They will have a 50/50 chance of being in either group. You will not make the choice to which group you are assigned. The two groups are Group A (cholesterol/lovastatin) and Group B (lovastatin only). The patient will not be informed of which group they are in and will not be informed of what their study medication is, allowing single-blinding. Researchers will not be masked. Initial enrollment will occur virtually. Enrolled subjects will be followed up at monthly intervals for three months via virtual check-in. At each visit, participants will undergo brief physical examination; additionally, clinical photographs of the lesion will be obtained. Photographs will be stored in the electronic medical record and stored in a departmental secure drive for further analysis of lesion features. At each visit the novel DSAP- General Assessment Scale and RAND36 QoL scale will be administered. Patients will be contacted via virtual check-in visits at weeks 4, 8, and 12. Patients will be asked about compliance and any adverse effects experienced. Participants will also be contacted by phone by study team member to assess for any adverse effects at weeks 2 and 6 of treatment. Compounded topical medication prescribed to subjects will be self-applied twice daily. These medications will be prepared by Tide Water Pharmacy Charleston, SC and Chemistry RX Philadelphia, PA. Chemistry Rx will ship the medications to the patients. They will be prepared so the study will remain single-blinded. The associated costs will not be covered by the research budget. Dermoscopic and clinical photographs will be subsequently analyzed for the presence of cornoid lamella. The team will record any additional dermoscopic or clinicals feature that may arise during the analyses. Frequency of dermoscopic and clinical features will be analyzed against clinical involution to find possible predictors.
Interventions
DRUGLovastatin 2%, 2% Cholesterol Cream
Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm.
DRUGLovastatin 2% Cream
Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm.
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* All patients 18 years and older with the diagnosis of disseminated superficial actinic porokeratosis.
Exclusion criteria
* Patients with allergies or contraindications to lovastatin or cholesterol * Female patients currently pregnant or lactating. * Female patients with plans to become pregnant. * Patients actively taking approved forms of long-term contraception (oral contraceptives, implantable intrauterine devices, or other hormone eluting implants) will be allowed to participate as long as they have no plan to become pregnant during the course of the study. A urine pregnancy test will be administered to these patients to confirm that they can be included in the study. * Inability or unwillingness of subject or legal guardian/representative to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Measurement of Treatment Efficacy Determined by DSAP-GASI Score (Disseminated Actinic Porokeratosis General Assessment Severity Index) | 12 weeks | The primary endpoint was the percentage of lesion clearance after 12 weeks of therapy using an exploratory clinical measure modified from a validated psoriasis index. The Disseminated Actinic Porokeratosis General Assessment Severity Index (DSAP-GASI) included plaque/rim elevation, scaling, and color (0= clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe). Lesions of each patient were graded by 2 blinded physicians before and after treatment. |
| Presence of Coronoid Lamella on Dermoscopy (or Photograph). | 12 weeks | Dermoscopic and clinical photographs will be subsequently analyzed for the presence of cornoid lamella (well circumscribed, erythematous macule with a peripheral rim of hyperkeratosis). The team will record any additional dermoscopic or clinicals feature that may arise during the analyses. |
| Actinic Keratosis Field Assessment Scale | 12 weeks | The Actinic Keratosis Field Assessment Scale measures the percent area covered by actinic keratosis on a scale of 0-4 (0 being 0% and 4 being \>50% total area on face or scalp), the severity of hyperkeratosis based upon size of lesion and degree of hyperkeratosis (considered positive findings if \>1 actinic keratosis with significant hyperkeratosis and \>5mm in diameter), and sun damage severity, measured positive (moderate or severe sun damage) or negative (none or mild damage), based upon severity of erythema, telangiectasia, inflammation, atrophy, and pigmentation disorders. This will be used to determine skin changes (described above) during treatment. A higher score would indicate a worse outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in Overall Appearance of DSAP Lesions | 12 weeks | Patients were asked if their overall appearance was better, unchanged, worse. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. Better overall improvement is reported in the data table. |
| Improvement in Size of DSAP Lesions | 12 weeks | Patients were asked if their lesion size was smaller, unchanged, or larger. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. The number of participants reporting smaller lesions is reported in the data table. |
| Application Frequency Influence on Disseminated Actinic Porokeratosis General Assessment Severity Index | 12 weeks | Measure if applying once or twice a day had an affect on treatment efficacy using the DSAP-GASI described in the primary outcome. Factors included plaque/rim elevation, scaling, and color. (0= clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe). Lower score indicates better outcome. |
| Improvement in Color of DSAP Lesions | 12 weeks | Patients were asked if their color was lighter, unchanged, darker. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. Lighter coloring is reported in the data table. |
| Pain and Itch Associated With Treatment | 12 weeks | Pain and Itch were measured as increased or decreased at weeks 0, 4, 8, and 12. Week 12 findings reported. |
| Improvement in Dermatology Quality of Life Index Questionnaire | 12 weeks | The patient quality of life scale asks 10 questions gaging how the patient skin condition is currently impacting their life. This questionnaire is a common validated tool, available free online. DLQI interpretation: no effect (0-1), mild effect (2-5), moderate effect (6-10), very large effect (11-20), extreme large effect (21-30). Lower scores represent improved quality of life. This was given after every visit at weeks 0, 4, 8, and 12 to access if the cream has contributed to quality of life improvement. The mean difference between the first (week 0) and last score (week 12) was used as the final improvement score. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Statin/Cholesterol Combination Group This arm will utilize 2% cholesterol and 2% lovastatin ointment. It will be compounded by a pharmacist. Ointment will be applied on lesional skin with occlusion twice daily for 12 weeks.
Lovastatin 2%, 2% Cholesterol Cream: Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm. | 17 |
| Statin Alone Group This arm will utilize 2% lovastatin ointment. It will be compounded by a pharmacist. Ointment will be applied on lesional skin with occlusion twice daily for 12 weeks.
Lovastatin 2%: Patients selected to the study will be randomly assigned to this arm. They will have a 50% chance of being placed in this arm compared to the other arm. | 14 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Statin Alone Group | Total | Statin/Cholesterol Combination Group |
|---|---|---|---|
| Age, Continuous | 57.3 years | 58.3 years | 59.2 years |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 14 participants | 31 participants | 17 participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 14 |
| other Total, other adverse events | 3 / 17 | 0 / 14 |
| serious Total, serious adverse events | 0 / 17 | 0 / 14 |
Outcome results
Primary
Actinic Keratosis Field Assessment Scale
The Actinic Keratosis Field Assessment Scale measures the percent area covered by actinic keratosis on a scale of 0-4 (0 being 0% and 4 being \>50% total area on face or scalp), the severity of hyperkeratosis based upon size of lesion and degree of hyperkeratosis (considered positive findings if \>1 actinic keratosis with significant hyperkeratosis and \>5mm in diameter), and sun damage severity, measured positive (moderate or severe sun damage) or negative (none or mild damage), based upon severity of erythema, telangiectasia, inflammation, atrophy, and pigmentation disorders. This will be used to determine skin changes (described above) during treatment. A higher score would indicate a worse outcome.
Time frame: 12 weeks
Population: Unable to accurately assess due to lack of in person visits during the covid 19 pandemic.
Primary
Measurement of Treatment Efficacy Determined by DSAP-GASI Score (Disseminated Actinic Porokeratosis General Assessment Severity Index)
The primary endpoint was the percentage of lesion clearance after 12 weeks of therapy using an exploratory clinical measure modified from a validated psoriasis index. The Disseminated Actinic Porokeratosis General Assessment Severity Index (DSAP-GASI) included plaque/rim elevation, scaling, and color (0= clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe). Lesions of each patient were graded by 2 blinded physicians before and after treatment.
Time frame: 12 weeks
Population: Treatment efficacy was based on investigator-standardized patient-documented photographs. Repeat photo documentation was obtained if image quality was inadequate or angle, lighting or location was not standardized to prior photos. Thirty-one subjects enrolled in the study, of which 24 provided clear pictures across all four visits (i.e. \~77%) and were considered in the efficacy analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Statin/Cholesterol Combination Group | Measurement of Treatment Efficacy Determined by DSAP-GASI Score (Disseminated Actinic Porokeratosis General Assessment Severity Index) | 50.0 Percent decrease in mean DSAP-GASI score |
| Statin Alone Group | Measurement of Treatment Efficacy Determined by DSAP-GASI Score (Disseminated Actinic Porokeratosis General Assessment Severity Index) | 51.4 Percent decrease in mean DSAP-GASI score |
Primary
Presence of Coronoid Lamella on Dermoscopy (or Photograph).
Dermoscopic and clinical photographs will be subsequently analyzed for the presence of cornoid lamella (well circumscribed, erythematous macule with a peripheral rim of hyperkeratosis). The team will record any additional dermoscopic or clinicals feature that may arise during the analyses.
Time frame: 12 weeks
Population: unable to complete due to COVID 19 pandemic causing virtual visits for most patients.
Secondary
Application Frequency Influence on Disseminated Actinic Porokeratosis General Assessment Severity Index
Measure if applying once or twice a day had an affect on treatment efficacy using the DSAP-GASI described in the primary outcome. Factors included plaque/rim elevation, scaling, and color. (0= clear, 1=almost clear, 2=mild, 3=moderate, and 4=severe). Lower score indicates better outcome.
Time frame: 12 weeks
Population: Data was analyzed against DSAP-GASI scores that had n=12 for each treatment arm. Frequency was also analyzed in the 24 participants selected for the DSAP-GASI. 8 of those participants happened to be once a day and 16 twice a day.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Statin/Cholesterol Combination Group | Application Frequency Influence on Disseminated Actinic Porokeratosis General Assessment Severity Index | 1.42 score on a scale |
| Statin Alone Group | Application Frequency Influence on Disseminated Actinic Porokeratosis General Assessment Severity Index | 1.54 score on a scale |
Secondary
Improvement in Color of DSAP Lesions
Patients were asked if their color was lighter, unchanged, darker. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. Lighter coloring is reported in the data table.
Time frame: 12 weeks
Population: The numbers in each group do not equal the total number of analyzed participants because some declined to answer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Statin/Cholesterol Combination Group | Improvement in Color of DSAP Lesions | 13 participants denoting a score of lighter |
| Statin Alone Group | Improvement in Color of DSAP Lesions | 12 participants denoting a score of lighter |
Secondary
Improvement in Dermatology Quality of Life Index Questionnaire
The patient quality of life scale asks 10 questions gaging how the patient skin condition is currently impacting their life. This questionnaire is a common validated tool, available free online. DLQI interpretation: no effect (0-1), mild effect (2-5), moderate effect (6-10), very large effect (11-20), extreme large effect (21-30). Lower scores represent improved quality of life. This was given after every visit at weeks 0, 4, 8, and 12 to access if the cream has contributed to quality of life improvement. The mean difference between the first (week 0) and last score (week 12) was used as the final improvement score.
Time frame: 12 weeks
Population: 3/31 participants did not return a questionnaire at visit 1 or 4. In the statin group 12/14 returned a questionnaire and 16/17 in the combination group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Statin/Cholesterol Combination Group | Improvement in Dermatology Quality of Life Index Questionnaire | 48 Percent improvement in quality of life |
| Statin Alone Group | Improvement in Dermatology Quality of Life Index Questionnaire | 38 Percent improvement in quality of life |
Secondary
Improvement in Overall Appearance of DSAP Lesions
Patients were asked if their overall appearance was better, unchanged, worse. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. Better overall improvement is reported in the data table.
Time frame: 12 weeks
Population: The numbers in each group do not equal the total number of analyzed participants because some declined to answer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Statin/Cholesterol Combination Group | Improvement in Overall Appearance of DSAP Lesions | 14 participants denoting a score of better |
| Statin Alone Group | Improvement in Overall Appearance of DSAP Lesions | 12 participants denoting a score of better |
Secondary
Improvement in Size of DSAP Lesions
Patients were asked if their lesion size was smaller, unchanged, or larger. The responses were collected at weeks 4, 8, and 12. Only the final visit (week 12) was used in analysis. The number of participants reporting smaller lesions is reported in the data table.
Time frame: 12 weeks
Population: The numbers in each group do not equal the total number of analyzed participants because some declined to answer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Statin/Cholesterol Combination Group | Improvement in Size of DSAP Lesions | 12 participants denoting smaller size |
| Statin Alone Group | Improvement in Size of DSAP Lesions | 11 participants denoting smaller size |
Secondary
Pain and Itch Associated With Treatment
Pain and Itch were measured as increased or decreased at weeks 0, 4, 8, and 12. Week 12 findings reported.
Time frame: 12 weeks
Population: Two participants did not complete the study from the statin group, thus were not allowed in final analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Statin/Cholesterol Combination Group | Pain and Itch Associated With Treatment | 5 Participants |
| Statin Alone Group | Pain and Itch Associated With Treatment | 1 Participants |
| Statin Alone Group Itch Decrease | Pain and Itch Associated With Treatment | 1 Participants |
| Statin Alone Group Itch Increase | Pain and Itch Associated With Treatment | 1 Participants |
| Statin/Cholesterol Combination Group Pain Decrease | Pain and Itch Associated With Treatment | 2 Participants |
| Statin/Cholesterol Combination Group Pain Increase | Pain and Itch Associated With Treatment | 0 Participants |
| Statin Alone Group Pain Decrease | Pain and Itch Associated With Treatment | 0 Participants |
| Statin Alone Group Pain Increase | Pain and Itch Associated With Treatment | 0 Participants |