Treating Actinic Keratoses With Natural Daylight PDT: Comparing Two Light Sensitizers (ALA and MAL) (2013-002108-15)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Joint Authority for Päijät-Häme Social and Health Care
Sponsor:
Information provided by (Responsible Party):
Joint Authority for Päijät-Häme Social and Health Care
ClinicalTrials.gov Identifier:
NCT01893203
First received: July 2, 2013
Last updated: April 22, 2014
Last verified: April 2014
  Purpose

Actinic keratoses (AKs) are superficial premalignant skin lesions that can progress into an invasive or metasthatic 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 sensitizer, which induces activation of protoporphyrin IX (PpIX) and phototoxic reaction destroying the cancer cells.

The approved photosensitizers in Europe are methylaminolevulenic acid cream, (MAL, Metvix™, Galderma), a patch containing 5-aminolevulenic acid (5-ALA, Alacare®, Spirig AG) and aminolevulenic 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 policlinical sensitizer absorption and illumination.

At the moment two photosensitizers have marketing authorization in Finland, ALA (Ameluz®) and MAL (Metvix™). Ameluz® holds a lower unit price and it's clearance rate compares to Metvix™ in LED-PDT. We are piloting a study comparing the cost-efficacy of these two light sensitizers in NDL-PDT. Our hypothesis is that there will be at least 0,30 difference in the histopathological curing of the lesions. Our other hypothesis is that Ameluz® with it's lower unit price results in reduced treatment costs and better cost-efficacy compared to Metvix™. The efficacy of the treatments will be assessed clinically, histopathologically, immunohistochemically and by hyper spectrum camera imaging.


Condition Intervention Phase
Actinic Keratoses (gr I-III)
Drug: ALA sensitizer
Drug: MAL sensitizer
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treating Actinic Keratoses With Natural Daylight PDT: Comparing Two Light Sensitizers (ALA and MAL)

Resource links provided by NLM:


Further study details as provided by Joint Authority for Päijät-Häme Social and Health Care:

Primary Outcome Measures:
  • Histopathological healing of actinic keratoses [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Difference between pain experienced by the patient: comparing symmetrical areas of face or scalp [ Time Frame: 1 day ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Primary treatment reaction [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 20
Study Start Date: August 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Actinic keratoses patients
First the anticipated treatment area will be degreased using ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz-light sensitizer on the field cancerized area on the other side of the face and Metvix-light sensitizer on the other. The sides will be randomized in blocks of two. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony or yard for 2 hour illumination with natural daylight to accomplish the phototoxic reaction. Maximum dosage of light sensitizer will be 2 grams. The treatment will be repeated after 2 weeks for thicker gr II-III lesions with the same protocol.
Drug: ALA sensitizer
First the anticipated treatment area will be degreased using ethanol. Then SPF20 sun protection cream will be applied on all sun-exposed areas of the skin. Then a 0,25mm layer application of Ameluz-light sensitizer on the field cancerized area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony or yard for 2 hour illumination with natural 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:
  • aminolevulenic acid
  • Ameluz
Drug: MAL sensitizer
First the anticipated treatment area will be degreased using 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-light sensitizer on the field cancerized area. After appropriate absorption time of 30 minutes, the patients will be taken to the hospital balcony or yard for 2 hour illumination with natural 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:
  • methylaminolevulenic acid
  • Metvix

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • actinic keratoses on boths sides of the face or scalp
  • age over 18 years
  • there must be atleast one ak of over 6mm on both sides
  • patients must be able to make the decision to attend independently

Exclusion Criteria:

  • pregnancy
  • lactation
  • lack of compliance
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01893203

Contacts
Contact: Mari Grönroos, PhD +358503708881 mari.gronroos@co.inet.fi

Locations
Finland
Päijät-Häme Central Hospital Recruiting
Lahti, Finland, 15850
Contact: Mari Grönroos, PhD    +358503708881    mari.gronroos@co.inet.fi   
Sponsors and Collaborators
Joint Authority for Päijät-Häme Social and Health Care
Investigators
Principal Investigator: Noora E Neittaanmäki-Perttu, MD Helsinki University Hospital
Principal Investigator: Toni T Karppinen, MD Päijät-Häme Central Hospital
Study Chair: Taneli Tani, PhD Päijät-Häme Central Hospital
Study Chair: Ilkka Pölönen, MSc Jyväskylä University
  More Information

No publications provided

Responsible Party: Joint Authority for Päijät-Häme Social and Health Care
ClinicalTrials.gov Identifier: NCT01893203     History of Changes
Other Study ID Numbers: R13073 / Q257, 2013-002108-15
Study First Received: July 2, 2013
Last Updated: April 22, 2014
Health Authority: Finland: Finnish Medical Agency

Additional relevant MeSH terms:
Keratosis
Keratosis, Actinic
Skin Diseases
Precancerous Conditions
Neoplasms
Methyl 5-aminolevulinate
Photosensitizing Agents
Dermatologic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 26, 2014