In this phase-1 trial, most parents applied the ceramide-dominant triple lipid mixture to the skin of their child on most days during the study period, and there were no major adverse reactions attributable to the intervention. Parents were also willing to start applying the cream within the first 2-3 weeks of life, when the skin barrier is most compromised even in health infants . Due to the lack of a control group, no conclusions can be made concerning the effect of the intervention on skin barrier, although the obtained TEWL values appear to be substantially lower than those reported previously in this age group (mean = 9.3 g/m2/hr, range = 7.2-10.5 for forearm for the current study compared with mean = 26 g/m2/hr for infants aged 3-6 months in a prior publication ). Adverse events that occurred were common conditions in this age group and did not appear to be related to the study treatment.
There are a number of other phase 1 and 2 trials currently being conducted to evaluate various topical interventions for improving the skin barrier function of infants at increased of developing eczema. One similar study is evaluating the effects of a standard emollients (Cetaphil, an oil-in-water cream) . We have chosen an emollient that contains ceramides, cholesterol and free fatty acids at a 3:1:1 ratio (which also contains 2% petrolatum) and has been formulated to correct the underlying lipid defects in eczematous stratum corneum . There is limited data available at this time [9, 13] comparing EpiCeram with cheaper emollients. A recent study has found that the efficacy of EpiCeram was no-greater than an over the counter petrolatum-based moisturiser (Aquaphor) for the management of mild-to-moderate atopic dermatitis, and that the cost effectiveness was far greater for the over the counter formulation . It should be noted that the previous study assessed the effects of these treatments for the management of symptoms for existing eczema, rather using it as a preventive strategy. Secondly, the observed results were obtained by applying the treatments three times per day . It would appear unlikely that parents would be able, or willing, to undertake such an intensive skin care regime for the prevention of eczema.
A potential role for EpiCeram in eczema prevention is supported by findings that: ceramide profile correlates with eczema , and applied ceramides rapidly incorporate into the nucleated layers of the epidermis . Furthermore, EpiCeram is formulated at an acidic pH (5.0), as lamellar body production and secretion of ceramides is impaired at the high pH of eczematous skin . Also, EpiCeram contains 2% petrolatum, which provides similar benefits of pure petrolatum, but without the greasiness , which is an important consideration for an eczema prevention strategy.
No adverse reactions to the study cream occurred in this small sample of infants. Although concerns have been raised about the toxic potential of excess ceramides, the pseudo-ceramide used in EpiCeram™ do not share these properties . There have been no reported events of toxicity caused by EpiCeram™ in the three years of marketing this product as a treatment for eczema. One of our institutional ethics committees questioned the application of this intervention to the face and hands of infants, due to the risk of ingestion of the cream. However, given that eczema generally commences on the scalp, face and neck , and that two of the infants developed symptoms of facial eczema, it will be important to apply the cream to the full body surface, including the face and hands, in future studies. Although the small amount of cream that can be ingested is unlikely to cause adverse events, given the novelty of this intervention and the vulnerability of the participant population, we will continue to monitor the safety of this intervention, including systemic and gastrointestinal reactions.
Importantly, this study provided useful information on recruitment strategy. Recruitment into this trial proved surprisingly difficult, as demonstrated by the high number of mothers approached to achieve 10 children completing this study. We also found a reasonably high rate (3/13 parents) who initially consented for their child to be enrolled in the study, but soon after decided to withdraw from the study, which indicates that "over recruitment" will need to be used in similar future studies. We trailed a range of potential recruitment strategies, finding that a post-natal approach was most efficient, due to the higher rate of recruitment, and minimising the delay from the expression of interest to the initiation of treatment. Anecdotally, we also observed that parents of children with the strongest family history of allergic disease, particularly those who had an older child with moderate to severe eczema, were most interested in being involved in this type of study.
This study has two important limitations. Firstly, although we did not observe any adverse skin effects of the study treatment, the relatively sample size means that we cannot exclude the possibility that this treatment may cause rarer adverse effects. Secondly, the lack of a control group precludes us from assessing if this treatment may help improve skin barrier function and reduce the risk of eczema. We are currently developing further trials to address these limitations.