The study was a prospective, randomised, double blind, placebo controlled trial of parallel group design, done in a single centre. We assessed participants at baseline and at 2, 4, 8, and 12 weeks.
We recruited male and female patients aged over 2 years attending our department for treatment of atopic dermatitis. To ensure that the age structure of the treatment groups was reasonably balanced, we stratified participants into two groups of equal size: those aged up to 12 and those aged over 12. We based the diagnosis of atopic dermatitis on the criteria of Hanifin and Rajka.13
We excluded pregnant and lactating women, and fertile women were required to use effective contraception. All volunteers (or parents for those under 16 years) provided written informed consent to participation in the study. We obtained verbal or written agreement from all children considered by the investigators and their parents to be old enough to understand the issues.
Essential Nutrition allocated borage oil or placebo treatment by using computer generated random numbers. Treatments were supplied in containers labelled with randomisation numbers in separate sequences for adults and children. These were allocated to patients in strict numerical sequence. Borage oil (Ropufa 25 N6, Roche Lipids Ltd) and placebo treatments were provided in matching capsules; placebo capsules contained liquid paraffin for adults and olive oil for children. Adults received four 500 mg capsules twice daily, providing 920 mg of γ linolenic acid for those receiving borage oil. Children received half this dose. We used liquid paraffin as placebo in adults, as this is considered to be the most inert placebo available and the dose was not large enough to act as a laxative. In children we used olive oil instead, to avoid any laxative effect of liquid paraffin. Neither placebo is considered likely to exert any beneficial or adverse effect on atopic dermatitis. To facilitate recruitment, we reduced the proportion of participants receiving placebo to 40%, and 60% received borage oil. We retained the treatment code in individual sealed envelopes for each patient. We did not break the blinding for any patient until the trial and all data entry were completed.
We allowed patients to use conventional treatment for atopic eczema throughout the study. We permitted no changes in concomitant treatment for two weeks before the study or for the duration of the study, except in the quantity and frequency of topical steroid application, which could be adjusted as needed in relation to the severity of the disease. We encouraged patients to apply the topical steroids only when needed. Permitted concomitant medications included emollient creams, bath oils, soap substitutes, and topical steroids classified in the British National Formulary as “mild,” “moderately potent,” or “potent” (but not “very potent” topical steroids). “Potent” topical steroids were prohibited for children. We allowed systemic antihistamines, but no other systemic treatment or ultraviolet light treatment was permitted. A minimum four week washout period was needed for patients who had received systemic steroids, psoralen plus ultraviolet A (PUVA), or other oral immunosuppressive treatment.
We assessed disease activity objectively at each visit by using the six area, six sign, atopic dermatitis (SASSAD) score.14
This well validated scoring system, which has been used in many trials on atopic dermatitis, involves assessment of six signs (erythema, exudation, excoriation, dryness, cracking, and lichenification) at six sites (hands, feet, arms, legs, head and neck, and trunk). Each sign is graded at each site on a four point scale (0-3, representing grades of none, mild, moderate, and severe). The maximum score theoretically possible is therefore 108.
To assess the severity of symptoms, patients used horizontal 10 cm visual analogue scales marked none at the left hand end and worst ever at the right. We assessed itching, sleep disturbance, and irritability in this way. We measured scores in millimetres from the left hand end, so that the maximum severity was 100. Participants made an overall assessment of response to treatment at the end of the treatment relative to the baseline, on a five point scale: worse, same, improved, much improved, or cleared. These assessments were also done on discontinuation of treatment in patients who were withdrawn. We recorded the need for topical steroid at each visit by using a five point scale: 1 = none, 2 = occasionally, 3 = alternate days, 4 = once daily, 5 = twice daily.
Participants assessed overall tolerability of the treatment on a four point scale: very good, good, fair, or poor. We elicited information on adverse events by using non-leading questions at each visit. In adults, we obtained blood samples for haematology, biochemistry (urea, electrolytes, and liver function tests), fasting serum cholesterol, and triglycerides on screening, at week 2, and the end of treatment.
We defined the primary response criterion prospectively as the mean change in total sign score at the end of treatment. We compared mean changes in score between baseline and end of treatment for each treatment arm by using a two tailed t test. Although these data are approximately normally distributed, we corroborated results with non-parametric methods (the Wilcoxon rank sum test).
The study was designed to have 80% power to detect a treatment response of 20% (that is, above the response to placebo), with a standard deviation (derived from existing data) of 35%, at a significance level of 0.05. We estimated that 120 participants would be needed. We anticipated that around 20% of participants would be withdrawn and therefore aimed to recruit 152 participants, comprising 76 adults and 76 children.
We did the analysis with the last available data for each participant who returned at least once after randomisation. We also did identical analyses on the protocol correct population comprising those participants who completed the trial. In figures and the last observations have been carried forward for patients who withdrew.
Six area, six sign, atopic dermatitis (SASSAD) scores throughout the trial (n=140; error bars show SE)
Use of topical corticosteroids assessed at each visit on a five point scale (n=140)