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Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL) (2013-002108-15)

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ClinicalTrials.gov Identifier: NCT01893203
Recruitment Status : Completed
First Posted : July 8, 2013
Results First Posted : July 11, 2016
Last Update Posted : July 11, 2016
Sponsor:
Information provided by (Responsible Party):
Joint Authority for Päijät-Häme Social and Health Care

Tracking Information
First Submitted Date  ICMJE July 2, 2013
First Posted Date  ICMJE July 8, 2013
Results First Submitted Date  ICMJE December 23, 2015
Results First Posted Date  ICMJE July 11, 2016
Last Update Posted Date July 11, 2016
Study Start Date  ICMJE August 2013
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 29, 2016)
Histological Lesion Clearance [ Time Frame: 0 (baseline) and 3 months ]
Punch biopsies were taken symmetrically on both treatment fields from equally graded >6 mm AKs prior to treatment and again at 3 months, blinded observer (pathologist). HE- and p53-stainings. Samples not fulfilling the criteria of an AK were defined as healthy or completely cleared. The p53 reactivity expressed as average percentage of positive nuclei in three consecutive high power fields from the region of highest reactivity (<10 % normal)
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2013)
Histopathological healing of actinic keratoses [ Time Frame: 3 months ]
We will take 3mm punch biopsies of similar looking AKs from both sides of the face or scalp before the treatment and 3 months after the treatment to assess the histopathological healing of actinic keratoses. We will also make immunohistochemical analyses of P53 chromosome mutations from the taken biopsies.
Change History Complete list of historical versions of study NCT01893203 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 29, 2016)
  • Pain [ Time Frame: 12 hours ]
    Pain using visual analog scale (VAS 0-10, where 0 is no pain and 10 is the worst pain imaginable) on both treatment sides is assessed in every 30 minutes during 2-hour sun-exposure and afterwards once in two hours until 9 p.m. (treatment day). Of these values, the mean maximal pain is assessed.
  • Clinical Lesion Clearance [ Time Frame: 3 months ]
    Clinical lesion clearance is observed by a blinded observer
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2013)
Difference between pain experienced by the patient: comparing symmetrical areas of face or scalp [ Time Frame: 1 day ]
Patients will be asked to fill visual analogue scales about pain experienced by the patients on each sides of the face or scalp. Pain is assessed after the treatment until the evening.
Current Other Pre-specified Outcome Measures
 (submitted: May 29, 2016)
Adverse Reactions [ Time Frame: 1 week ]
Adverse reactions are evaluated by blinded observer at one week after treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction.
Original Other Pre-specified Outcome Measures
 (submitted: July 2, 2013)
  • Primary treatment reaction [ Time Frame: 1 week ]
    The primary treatment reaction will be single-blindedly assessed one week after the treatment. A dermatologist will assess which side of the face or scalp presents a stronger reaction.
  • Dermatoecological analyses of the treatment costs [ Time Frame: 3 months ]
    Researchers will analyze the cost-efficacy of the treatments using decision tree, sensitivity analysis, ICER and QALY-analyses to decide with treatment modality is more preferrable. The differences in cost-efficacy will most likely depend on the light sensitizer costs and their efficacy on the treated lesions.
  • Hyper spectrum imaging [ Time Frame: 3 months ]
    Hyper spectrum camera images will be taken before treatment and 3 months after the treatment to assess the healing of field cancerization and actinic keratoses areas.
 
Descriptive Information
Brief Title  ICMJE Daylight-PDT for AKs: Comparing Two Photosensitizers (BF-200 ALA and MAL)
Official Title  ICMJE Treatment of AKs With Daylight-PDT: Comparing Two Photosensitizers (BF-200 ALA and MAL)
Brief Summary The aim of the study is to compare the efficacy of two photosensitizers, methyl-aminolaevulinate (MAL) and 5-aminolaevulinic nanoemulsion (BF-200 ALA) in the treatment of facial actinic keratosis. We use randomized, double-blinded prospective study design. The efficacy will be assessed clinically, histopathologically and immunohistochemically.
Detailed Description

Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metastatic squamous cell carcinoma. AKs can be treated with photodynamic therapy (PDT), of which cure rate compares to cryo surgery with an excellent cosmesis. In PDT the AK lesions are first curettaged, then a photosensitizer is applied on the skin and let to absorb for 3 hours. The skin is illuminated using a blue or red light source light source depending on the photosensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells.

The approved photosensitizers in Europe are methyl-aminolevulinic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulinic acid (5-ALA, Alacare®, Spirig AG) and 5-aminolevulinic acid gel (BF-200 ALA, Ameluz®, Biofrontera AG) to be used with a red LED light (630-635 nm). In North America a 5-aminolevulinic acid stick (5-ALA, Levulan® Kerastick) can also be used with a blue light source (417 nm).

PpIX absorption peaks are within the visual spectrum of light, which allows PpIX daylight activation. During natural daylight PDT (NDL-PDT) protocol, PpIX is continuously activated during its development, whereas in conventional PDT (LED-PDT) using red LED lamps, large amounts of accumulated PpIX are momentarily activated.

Since skin field cancerization refers to presence of different degrees of visible and invisible dysplastic changes, the whole area should be treated to prevent the development of non-melanoma skin cancers (NMSCs). NDL-PDT enables treatment of field cancerization in one sitting whereas LED-PDT may need repeated illuminations to cover the whole area. NDL-PDT results in enhanced cost-efficacy due to reduced staff expenses, since there's no need for sensitizer absorption and illumination.

At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). We are piloting a study comparing the efficacy of these two light sensitizers in NDL-PDT. The efficacy of the treatments will be assessed clinically, histopathologically and immunohistochemically.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Multiple Actinic Keratoses
Intervention  ICMJE
  • Drug: BF-200 ALA cream
    The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then sun protection factor (SPF) 20 cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz cream on the area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.
    Other Names:
    • 5-aminolaevulenic acid nanoemulsion
    • Ameluz
  • Drug: MAL cream
    The symmetrical treatment areas will be randomized for treatments. First the treatment area will be wiped ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Metvix cream on the area. After appropriate absorption time of 30 minutes, the patientswill be taken to the hospital balcony for 2 hour illumination with daylight to accomplish the phototoxic reaction. Maximum dosage will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.
    Other Names:
    • methylaminolevulinic acid
    • Metvix
Study Arms  ICMJE BF-200 ALA vs MAL
BF-200 ALA cream and MAL (Metvix, Galderma) used in a randomized split-face design
Interventions:
  • Drug: BF-200 ALA cream
  • Drug: MAL cream
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 29, 2016)
14
Original Estimated Enrollment  ICMJE
 (submitted: July 2, 2013)
20
Actual Study Completion Date  ICMJE December 2014
Actual Primary Completion Date December 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • actinic keratoses symmetrically on face or scalp
  • age over 18 years
  • there must be at minumum one ak sized 6mm2 symmetrically on both sides
  • patients must be able to make the decision to attend independently

Exclusion Criteria:

  • pregnancy
  • lactation
  • lack of compliance
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01893203
Other Study ID Numbers  ICMJE R13073 / Q257
2013-002108-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Joint Authority for Päijät-Häme Social and Health Care
Study Sponsor  ICMJE Joint Authority for Päijät-Häme Social and Health Care
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Noora E Neittaanmäki-Perttu, MD Helsinki University Central Hospital
Principal Investigator: Toni T Karppinen, MD Päijänne Tavastia Central Hospital
Study Chair: Taneli Tani, PhD Päijänne Tavastia Central Hospital
PRS Account Joint Authority for Päijät-Häme Social and Health Care
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP