Primary: to evaluate and compare the efficacy of:1) PDL treatment followed by topical sirolimus application after Er:Yag laser ablation of the stratum corneum in PWS 2) PDL treatment followed by topical sirolimus application without Er:Yag laser…
ID
Source
Brief title
Verkorte titel: New treatment for port wine stains
Condition
- Skin vascular abnormalities
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Percentage clearance of the treated area assessed colorimetrically (Minolta
colorimeter).
Secondary outcome
- Percentage clearance of the treated area assessed by standardized digital
colour image analysis.
- Percentage clearance of the treated area assessed by photographic evaluation
by an expert panel.
- To evaluate the improvement in quality of life;
- Patient discomfort and pain experienced during and following treatment;
- Patient-reported symptoms and side-effects;
- Systemic sirolimus exposure;
- Treatment satisfaction.
Background summary
Pulsed Dye Laser (PDL) treatment is currently the gold standard for the
treatment of Port Wine Stains (PWS). However, a protracted course of treatments
is usually necessary to obtain a clinically significant degree of lesion
blanching. This appears to be (partly) due to neo-angiogenesis. We hypothesize
that the efficacy of standard PDL treatment can be greatly enhanced by
subsequent application of topical sirolimus (Rapamycin or RPM). The rationale
for this combined treatment is that by application of sirolimus after PDL,
neo-angiogenesis will be inhibited, which may attenuate the reformation and
reperfusion of PWS blood vessels disrupted by laser photothermolysis. By using
the Erbium Yag (Er:Yag) laser for ablation of the stratum corneum in addition,
we could facilitate superior penetration and local skin distribution of
sirolimus and possibly inhibit neo-angiogenesis in deeper parts of the dermis.
This combined treatment may result in a higher therapeutic efficacy in terms of
PWS blanching.
Study objective
Primary: to evaluate and compare the efficacy of:
1) PDL treatment followed by topical sirolimus application after Er:Yag laser
ablation of the stratum corneum in PWS
2) PDL treatment followed by topical sirolimus application without Er:Yag laser
ablation of the stratum corneum
3) PDL treatment only
4) Sirolimus application only
Secondary:
- To evaluate the improvement in quality of life;
- To evaluate patient discomfort and pain experienced during and following
treatment;
- To evaluate patient-reported symptoms and side-effects;
- To assess systemic sirolimus exposure after local application by measuring
serum concentrations;
- To evaluate treatment satisfaction.
Study design
Open label pilot study.
Intervention
In the first treatment period all patients will receive a total of five
treatments with two week intervals. Every patient will receive the following
four treatments (utilizing a template with separate squares of 1cm2): 1) PDL
treatment followed by topical sirolimus application after Er:Yag laser ablation
of the stratum corneum compared with 2) PDL treatment followed by topical
sirolimus application without Er:Yag laser ablation of the stratum corneum, 3)
PDL treatment only and 4) sirolimus application only. After the six months
follow-up period, during the second treatment period, patients will receive an
additional five treatments of the adjacent cosmetic unit of the treated part of
the PWS, employing the most successful of the four treatment modalities as
evaluated after the first treatment period.
Study burden and risks
The whole treatment period will entail 16 visits to the outpatient department.
Percentage clearence will be assesed colormetrically by using a Minolta
Colorimeter. Digital photographs will be assessed by colour image analysis and
by an expert panel. Patients will be asked to fill in questionnaires about
discomfort and pain experienced during and following treatment (VAS scores).
Patient satisfaction (0-100 scale) and quality of life (DLQI) will be
evaluated. Blood samples will be taken regularly to assess safety. Also serum
concentrations of sirolimus will be assessed in order to evaluate potential
systemic exposure. We propose the use of a topical formulation of sirolimus
(Rapamune®) to minimize the risks associated with systemic sirolimus exposure.
Burg. sJacobplein 51
Rotterdam 3015 CA
NL
Burg. sJacobplein 51
Rotterdam 3015 CA
NL
Listed location countries
Age
Inclusion criteria
• Subject has provided informed consent;
• Subject is >= 18 years of age at time of screening;
• Subject has an extra-facial homogenous PWS;
• The PWS is large enough in size to fit one of the templates (at least 11 cm x 3 cm or 7 cm x 5 cm);
• Subject has not received any laser treatment of the PWS in the last 3 months (in the treatment area);
• The PWS has a minimal erythema grading score of 3 (on a 4 point scale) in the opinion of the investigator;
• Screening blood safety values are within normal parameters or regarded as not clinically significant in the opinion of the investigator.
Exclusion criteria
• PWS with a nodular/hypertrophic component in the treatment area;
• PWS on cosmetically unacceptable locations in the opinion of the investigator;
• For women: pregnant or breast feeding during the treatment period;
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using adequate contraceptive measures; Effective contraception is defined as either:
o Barrier method of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicide.
The following methods are considered more effective than the barrier method and are also acceptable:
o Total abstinence (when this is in line with the preferred and usual lifestyle of the subject).
o Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before participating in the study.
o Male sterilization (at least 6 months prior to screening). For female subjects on the study, the vasectomized male partner should be the sole partner for that subject.
o Use of oral, injected or implanted hormonal methods of contraception or other forms, intrauterine device (IUD) or intrauterine system (IUS)
NOTE: Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago.
• Subject is known to have immune deficiency, or is immune compromised (including immunosuppression induced by medication);
• Known allergy to sirolimus or other constituents of the study medication;
• Incapacitated subjects;
• Any medical or psychiatric condition which, in the investigator*s opinion, would preclude the participant from adhering to the protocol or completing the study per protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-004834-14-NL |
| CCMO | NL47292.078.13 |