Potential Impact of Patient Vitamin D Status in AK Response to MAL-PDT (PDT)

July 31, 2020 updated by: Luis Antonio Torezan, University of Sao Paulo

Efficacy of Calcipotriol Assisted MAL-PDT Versus Conventional MAL-PDT for Actinic Keratosis: a Randomized and Controlled Study

In topical photodynamic therapy (PDT) for non-melanoma skin cancers, a photosensitizing prodrug, 5-aminolaevulinic acid (ALA) or its methylated ester, methyl aminolevulinate (MAL), is converted to the endogenous photosensitizer protoporphyrinIX (PpIX).

Reduced response rates are observed in thicker skin lesions, which may be due to insufficient PpIX accumulation within the target tissue.

To enhance PpIX production,several physical and chemical pretreatments have been suggested. One of the chemical substances proposed to stimulate PpIX production is vitamin D because of its ability of being a keratinocyte pro-differentiating hormone.

Based on in vitro and in animal model studies, we propose to study the potential impact of patient vitamin D pre-treatment in AK response to MAL-PDT.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

A randomized, controlled Split -scalp study with Calcipotriol Assisted MAL-PDT versus conventional MAL-PDT for actinic keratosis (AK) is proposed.

Twenty patients ( male gender only) with symmetrically distributed multiple AK lesions on the scalp will be included. Patients must have at least five AKs per field to be eligible.

After simple randomization, one half of the scalp will be treated with Calcipotriol ointment 50 mcg/g (Daivonex, Leo Pharma, Denmark) for 15 consecutive days.

After this period, the entire scalp will be submitted to topical PDT with Methylaminolevulinate 16% (Metvix, Galderma France) under occlusion for 90 minutes and then, illuminated with a light source consisting of a Light Emitting Diode device (LED) at 635 nm ( Aktilite - Photocure, Norway). The total light dose will be 37J/cm2.

Immediately before and after illumination with LED, measurements of the fluorescence intensity will be taken in 3 isolated spots in both sides of the scalp with a spectroscopy deviceUSB 2000+ ( Ocean Optics ® - Dunedin, Fl, USA).

AK lesions will be counted and mapped by a dermatologist not involved in the study before and after 3 months.

All patients will be advised to apply sunscreens 50 + 3x/day for the following 7 days after the procedure.

A 0-10 Visual Analogue Scale (VAS) will be used to measure the pain intensity during the illumination.

Records will be taken after 90 days and compared between sides: side effects, AK lesion response and pain level intensity. Also, a long term follow up will be provided at 6 and 12 months after.

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Brazil
    • SP
      • Sao Paulo, SP, Brazil, 04543120
        • Universidade de São Paulo
      • Sao Paulo, SP, Brazil
        • Hospital das Clinicas Universidade Sao Paulo

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

50 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • male gender
  • at least six AKs per field

Exclusion Criteria:

  • history of photosensitivity related disorders
  • active infectious disease,
  • immunosuppression
  • laser or any cosmetic treatment in the previous 6 months
  • other topical agents in the treatment area such as retinoids, 5-fluorouracil,imiquimod or diclofenac sodium in the previous 3 months
  • allergy to MAL or excipients of the cream
  • poor patient compliance.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Conventional MAL-PDT
Conventional topical PDT with Methylaminolevulinate 16% in one half of the scalp with multiple AKs.
Other: Conventional MAL-PDT
Curettage of lesions and application of MAl cream 16% for 90 minutes under occlusion followed by LED 635 nm illumination at 37 J/cm2 total dose
Other: Calcipotriol assisted MAL-PDT
Calcipotriol ointment 50 mcg/g applied once a day for 15 consecutive days in one half of the scalp, before Conventional topical PDT
Other: Calcipotriol assisted MAL-PDT
Calcipotriol 50 mcg/g for 15 days prior to PDT. Curettage of lesions and application of MAl cream 16% for 90 minutes under occlusion followed by LED 635 nm illumination at 37 J/cm2 total dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes From Baseline in Actinic Keratosis - Lesion Base Count.
Time Frame: Change from baseline, 90 days, 180 days and 12 months after the PDT

To compare the efficacy of topical PDT alone versus Calcipotriol assisted PDT for AKs on the scalp.

The values in the data table represent the mean (+sd) number of lesions on each side at 3, 6 and 12 months post intervention.

Lesion counts include lesions that have not been cleared and also newly emerged lesions ( if new lesions emerge on the treated field) At baseline: number of AKs was 290 on the CAL-PDT side and 284 on the conventional side.
Change from baseline, 90 days, 180 days and 12 months after the PDT
Percentage of Actinic Keratosis (AK) Lesions Cleared
Time Frame: Change from baseline, 90 days, 6 months and 12 months after PDT

AK clearance after PDT and comparison between the sides The values in the data table represent the percentage of AK clearance on each side at 3, 6 and 12 months post intervention.

At baseline: 290 on the CAL-PDT side and 284 on the conventional side.
Change from baseline, 90 days, 6 months and 12 months after PDT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pain Scores Immediately Post Illumination
Time Frame: immediately after intervention

Measurement of pain during LED illumination and comparison between the sides with a visual analogue scale (VAS), considering 0 as absence of pain and 10 as the most severe pain.

At baseline, before the illumination, there is an absence of pain, which means Score 0 (zero) for all participants before the procedure.

Pain is reffered during and after the illumination and measured with the VAS scale, reported by each patient.
immediately after intervention
Change From Baseline in Fluorescence Intensity of PPIX
Time Frame: Baseline and 10 minutes after illumination

Measurement of PPIX fluorescence on both sides of the scalp before and immediately after LED illumination PpIX fluorescence was measured in three different spot areas on the scalp before and immediately after PDT on each side.

The measurements were taken noninvasively in the areas where PpIX fluorescence was more intense, with a handheld fluorescence photometer (USB 2000+ spectroscopy device; Ocean Optics, Dunedin, FL, U.S.A.). The photometer illuminates a circular skin area with a diameter of 1 cm with blue light (400-420 nm), matching the Soret band of PpIX at 405-420 nm. By measuring excitation wavelengths at 600- 700 nm, the corresponding red PpIX fluorescence intensity at 633 nm is detected. Measurements were taken in arbitrary units. The mean PpIX fluorescence value for each side was calculated before and after the treatment.
Baseline and 10 minutes after illumination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo

Investigators

  • Principal Investigator: Luis A Torezan, MD, Hospital das Clinicas FMUSP Sao Paulo

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

October 1, 2016

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

April 1, 2020

Study Registration Dates

First Submitted

August 10, 2016

First Submitted That Met QC Criteria

August 24, 2016

First Posted (Estimate)

August 25, 2016

Study Record Updates

Last Update Posted (Actual)

August 4, 2020

Last Update Submitted That Met QC Criteria

July 31, 2020

Last Verified

July 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 08/2016

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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.

Clinical Trials on Actinic Keratosis

Clinical Trials on Conventional MAL-PDT

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Angola

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe