DOI: 10.1111/jdv.

14095 JEADV

ORIGINAL ARTICLE

Efcacy of an emollient cream in the treatment of xerosis in

diabetic foot: a double-blind, randomized, vehicle-
controlled clinical trial
J. Martini,1 C. Huertas,2 V. Turlier,3 C. Saint-Martory,3 A. Delarue4,*
1
Endocrinology Department, Rangueil University Hospital, Toulouse, France
2
Podology Unit, Purpan University Hospital, Toulouse, France
3
Pierre Fabre Dermo-Cosme
tique, Centre de Recherche sur la Peau, Ho
^tel-Dieu, Toulouse, France
4
Pierre Fabre Dermatologie, Lavaur, France
*Correspondence: A. Delarue. E-mail: alain.delarue@pierre-fabre.com

Abstract
Background Peripheral neuronal impairment compromises foot health in patients with diabetes. Clinically, xerosis is
the most common mild complication, but it should not be underestimated. An effective treatment must be able to restore
the cutaneous barrier and prevent water loss, to maintain adequate hydration and protection.
Objective This study aimed to assess the efcacy of an emollient cream on foot xerosis in patients with diabetes.
Methods This is a prospective, multicenter, randomized, double-blind contralateral vehicle-controlled study in 57
patients with diabetes. Patients were treated twice daily for 27  2 days with the study emollient containing glycerol
15%, liquid and soft parafn 10%, glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol
600, trolamine, propyl parahydroxybenzoate and puried water (Dexeryl; Pierre Fabre Medicament, Boulogne, France)
or its vehicle (glycerol monostearate, stearic acid, polydimethylcyclosiloxane, silicone oil, macrogol 600, trolamine, pro-
pyl parahydroxybenzoate and puried water). Efcacy was assessed after a 28-day treatment period using a validated
score [Xerosis Assessment Scale (XAS) score], instrumental measurements and subjective assessment.
Results The XAS score decreased to 3.2  2.6 points with the emollient and 4.1  2.3 with the vehicle (P = 0.001).
Improvement was observed from day 14 (P = 0.012). Compared with the vehicle, the emollient also signicantly
improved the overall skin score, hydration index, D-Squame (CuDerm Corporation, Dallas, TX, USA) test, skin rough-
ness and patients opinions.
Conclusion Treatment with an emollient is effective for improving foot xerosis in patients with diabetes.
Received: 25 September 2016; Accepted: 9 November 2016

Conicts of interest
JM has no conicts of interest. CH is a consultant for Pierre Fabre Consumer Healthcare. VT, CSM and AD are
Pierre Fabre employees.

Funding sources
This clinical trial was funded by Pierre Fabre.

Introduction from peripheral neuronal impairment. However, these com-

Patients with diabetes frequently present skin changes result-
ing from chronic hyperglycaemia. Demirseren and col-
leagues1 reported a 79.3% prevalence of skin diseases among
a group of 750 patients with diabetes, with xerosis being the
most common complication related to diabetes mellitus.1
Fifty per cent of all reasons for hospitalization among
patients with diabetes are foot-related problems.2 Xerosis,
hyperkeratosis and fissures are mild complications resulting
plications are risk factors for infections and ulcers, the most
serious disorders affecting diabetic feet which can lead to
amputation.3
The use of an emollient is part of recommended foot hygiene
to prevent diabetic foot complications.2,4 Moreover, the effec-
tiveness of skin hydration with moisturizers should be evaluated
in this special population. A few studies have shown an improve-
ment in diabetic foot xerosis with the use of moisturizers;

JEADV 2016 2016 European Academy of Dermatology and Venereology

2 Martini et al.
however, improvements were mainly evaluated through subjec-
tive assessment.3,5,6
We evaluated the use of an emollient cream in the treatment
of xerosis in diabetic foot. This study aimed to demonstrate the
efficacy of the emollient cream through objective and subjective
assessments using a validated score, instrumental measures and
patients opinions.
Methods
Study design
This was a prospective, multicenter, randomized, double-blind,
contralateral vehicle-controlled study to assess the efficacy of an
emollient cream in the treatment of xerosis in diabetic foot.
Ethics
The study was carried out in accordance with the Declaration of
Helsinki, the International Committee for Harmonization
(ICH) Guidelines for Good Clinical Practice (GCP) and French
law in force. Patients provided written informed consent before
the beginning of the study.
Study population
Eligible subjects were aged 1870 years, presenting with type 1
or 2 diabetes, dry skin on the feet and not having applied topical
emollients or keratolytic products for the previous 2 weeks. At
inclusion, the nine-point Xerosis Assessment Scale (XAS) score3
had to be between 4 and 6 (Table 1), with a maximum differ-
ence of one point between the two feet. The main non-inclusion
criteria were foot injury (except uncomplicated fissure), threat-
ening hyperkeratosis, hyperkeratotic disease unrelated to dia-
betes, significant disturbances of static feet or arterial
insufficiency.
Table 1 Xerosis Assessment Scale3
Grade Description
0 Normal skin
1 Few minute akes
Skin with few minute akes
2 Many undifferentiated skin akes
Skin with many undifferentiated skin akes
3 Some polygonal scales
Skin with some polygonal scales
4 Moderate number of polygonal scales
Skin with moderate amount of polygonal scales
5 Large number of polygonal scales
Skin with large number of polygonal scales
6 Fissuring between scales
Skin with small, supercial ssures between polygonal scales
7 Moderate deep ssuring between scales
Skin with moderate deep ssures
8 Deep ssuring
Skin with deep ssures
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Study treatment
Patients were treated twice a day for 27  2 days with the study
emollient containing glycerol 15%, liquid and soft paraffin 10%,
glycerol monostearate, stearic acid, polydimethylcyclosiloxane,
silicone oil, macrogol 600, trolamine, propyl parahydroxyben-
zoate and purified water (Dexeryl; Pierre Fabre Medicament,
Boulogne, France), or its vehicle (glycerol monostearate, stearic
acid, polydimethylcyclosiloxane, silicone oil, macrogol 600,
trolamine, propyl parahydroxybenzoate and purified water).
Emollient treatment was randomly allocated to the right or left
foot, with the other foot treated with the vehicle. The random-
ization list with parallel groups and a block size of four was gen-
erated by the Clinical Pharmacy Department using proprietary
software, and the list was previously validated by the Biometry
Department. Treatments were provided in identical, sequentially
numbered containers, and investigators assigned treatments to
patients on the basis of the sequence number. Thus, patients,
investigators and pharmacists remained blinded to which treat-
ment (emollient or vehicle) was supplied.
Careful cleaning of the hands was performed before each
application, and A-Derma dermatological soap (A-Derma,
Lavaur, France) was provided for foot hygiene.
Assessments
Qualitative assessments were performed through clinical assess-
ment of xerosis using the validated XAS score,3 an overall skin
score [sum of XAS (rated 08), skin roughness (rated 02), and
hyperkeratosis (rated 02)], the number of feet presenting fis-
sures, deep fissures, hyperkeratosis, threatening hyperkeratosis
and xerosis, and the subjects opinion using a 100-mm visual
analog scale [VAS; rated from 0 (not effective/not pleasant) to
100 (very effective/very nice)].
Quantitative assessments consisted of the skin hydration
index (HI) by Corneometry (Corneometer; Courage+ Khazaka,
Cologne, Germany), desquamation by D-Squame instant tester
with image analysis, which provides information on the quantity
and quality of skin scaliness or flakiness,7 and skin relief by sili-
con replicas with image analysis (Dermatop and Toposurf,
Eotech, Marcoussis, France).8 The latter assessment characterizes
the skin surface with the following topographic parameters: Spa
(arithmetic mean of roughness), Sdev or developed area (pro-
portion of relief contained in an image), SPtm (mean difference
between peaks and troughs).
End points
After one screening visit, investigators evaluated each patient at
inclusion [day 0 (D0)], then at D14 and D28 visits.
The primary objective was assessed by the change in XAS
score between baseline and D28. Secondary end points were the
evolution of XAS score at D14 and the overall skin score, the
number of feet presenting fissures, deep fissures, hyperkeratosis,
threatening hyperkeratosis and xerosis at D14 and D28,
2016 European Academy of Dermatology and Venereology
Emollient cream improves xerosis in diabetic foot 3

instrumental evaluation of the HI by corneometry and xerosis Results

by image analysis on D-Squame test at D14 and D28, measure- Investigators planned the inclusion of 56 evaluable patients. A
ment of skin relief at D14 and D28, and subjects opinions total of 65 patients were selected and, of these, 57 patients were
regarding treatment. randomized. Figure 1 shows a flow chart of the study popula-
Treatment-emergent adverse events (TEAEs) and serious tion. Patient characteristics at baseline are described in Table 2.
adverse events (SAEs) were recorded by investigators up to D28 The study population (mean age: 58.3  9.8 years) presented
and defined according to ICH Guidelines for GCP. slightly more females (51.8%) than males. The mean duration of
diabetes was 11.63  8.19 years, and 27 of 57 patients presented
Statistical analysis a peripheral neuropathy.
Demographics and other characteristics were described at base-
line. All statistical tests were bilateral, with a significance level of Efcacy outcomes
0.05. At baseline, feet characteristics were similar for both treatment
The Wilcoxon rank-signed test was used for the analysis of groups. After 27  2 days of treatment, mean XAS scores (pri-
the primary end point, foot xerosis at D14 and the overall skin mary end point) were 3.2  2.6 and 4.1  2.3 in the emollient
score.
Values of corneometry, D-Squame test and patients opinion
were analysed using the paired Students t-test or the Wilcoxon Table 2 Patient characteristics at baseline (data are presented as
rank-signed test. Analyses for the number of feet with fissures, mean  SD unless stated otherwise)
deep fissures, hyperkeratosis, threatening hyperkeratosis and Characteristic Value
xerosis, and for skin relief parameters, were descriptive. Gender (%) Female: 51.8%; male: 48.2%
Sample size estimation was based on the primary criterion for Age (years) 58.3  9.8
paired data (skin dryness on the foot evaluated by XAS after Weight (kg) 81.6  16.2
27  2 days of treatment), according to the following hypothe- Height(cm) 166.1  11.4
ses: an expected 0.8 point difference (XAS) between Dexeryl Body mass index (kg/m2) 29.69  5.75
cream and its vehicle this was based on the results published in Blood pressure (mmHg) 139.4  17.2 and 79.1  9.9
Pham et al.3, where a 1.2-point difference was observed between Heart rate (bpm) 70.4  7.4
an emollient containing keratolytics (urea 10%, lactic acid 4%) History of diabetes (years) 11.63  8.19
and its vehicle, an estimated standard deviation of 2.5, an a risk Feet with neuropathy (n) 27

of 0.05, a b risk of 0.1 (= power 90%) and a correlation coeffi-

cient of 0.5 for the right foot/left foot for the same subject. With
P = 0.012 P = 0.001
these hypotheses and taking into account premature with-
drawals, it was calculated that 65 patients would need to be
Xerosis Assessment Score

Dexeryl
included in order to obtain 56 evaluable patients. Vehicle
5.0

2.5
Selected
n = 65 Not included, not randomized, n = 8
Not meeting selection criteria, n = 2 0.0
Baseline D14 D28
Not meeting inclusion criteria, n = 4
Assessment time
Not attending inclusion visit, n = 1
Included and randomized Serious adverse event, n = 1
Figure 2 Xerosis Assessment Scale (XAS) score at baseline and
n = 57
at day 14 (D14) and day 28 (D28) after treatment with emollient and
vehicle.
Withdrawal of consent, n = 1

Safety population
n = 56 Table 3 Overall skin score at baseline and at day 14 (D14) and
day 28 (D28) after treatment with emollient (Dexeryl) and vehicle
Personal reasons, n = 1
Serious adverse event, n = 1 Dexeryl Vehicle P-value

Efficacy population Baseline 7.6  1.4 7.6  1.4 NS

n = 54 D14 5.1  2.9 5.9  2.8 0.0023
D28 3.7  3.0 5.0  2.9 0.0002
Figure 1 Study ow diagram.
NS, non-signicant.

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4 Martini et al.

Table 4 Results of the D-Squame test at baseline and at day 14 Baseline Day 14 Day 28
(D14) and day 28 (D28) after treatment with emollient (Dexeryl) and
vehicle

Dexeryl
Dexeryl Vehicle P-value
At baseline: mean (SD)
SURFT 87 237.6 (87 807.0) 84 447.8 (81 900.5) NS
SMOD 51.44 (24.57) 48.24 (18.69) NS
MOD 25.81 (33.91) 22.59 (26.61) NS

Vehicle
HI 8.97 (7.12) 7.55 (4.47) NS
At D14: mean (SD)
SURFT 64 596.2 (84 304.9) 70 397.1 (85 279.1) NS
SMOD 34.97 (15.07) 37.23 (14.66) 0.043 Protocol V00034CR303- Patient SeqID407

MOD 14.83 (20.52) 16.29 (21.93) NS

Figure 3 Example of skin relief and ssures in a patient with xero-
HI 4.72 (3.92) 4.71 (2.97) NS
sis in diabetic foot. Photographs were taken at baseline and at day
At D28: mean (SD)
14 and day 28 after treatment. The patient received emollient on
SURFT 50 068.4 (75 579.5) 60 586.4 (76 508.3) <0.001 one foot (top panel) and vehicle on the other foot (lower panel).
SMOD 30.95 (11.03) 36.80 (13.09) 0.004
MOD 10.70 (15.34) 14.21 (18.86) <0.001
HI 3.72 (3.33) 5.07 (4.05) 0.0015

More patients wanted to continue treatment with the emol-
NS, not signicant; SURFT, Total Surface Area of squames (mm ); MOD,
Mean Optical Density of squames; SMOD, Mean Optical Density of squames
lient only (44.4%) than with the vehicle only (29.6%). No
over threshold; HI, Heterogeneity Index. patient refused both treatments.

and vehicle groups, respectively (P = 0.001) (Fig. 2). The XAS
score decreased after 14  2 days of treatment in both groups
( 1.3 vs. 0.9) (Fig. 2).
As shown in Table 3, the overall skin score was superior in
the emollient group (P < 0.01). No differences were observed in
the number of feet presenting fissures, deep fissures, hyperker-
atosis, threatening hyperkeratosis and xerosis.
Skin hydration on the back of the foot improved during treat-
ment, with a mean HI increase at D14 of 9.52  8.71 with the
emollient and 6.61  7.03 with the vehicle (P = 0.029), and
10.46  8.30 vs. 6.86  8.08, respectively, at D28 (P = 0.005).
All parameters of the D-Squame test improved to a greater
extent with the emollient than with the vehicle: the amount of
squamous material was lower, with thinner and smaller scales,
spread more regularly over the sample. All differences were sta-
tistically significant at D28 (Table 4).
Skin relief measurements showed a greater reduction in the
emollient group compared to the vehicle group. For the ampli-
tude parameters, SPa and SPtm, respective changes were 34.4
vs. 25.2 lm and 70.5 vs. 117.1 lm; for the area parameter,
Sdev, the change was 5.4 vs. 3.3%, reflecting a decrease in
the roughness of the skin (Fig. 3).
Patients assessments (by VAS) at the end of the study showed
significantly greater satisfaction for treatment efficacy for the
foot treated with the emollient (73.2  25.3 mm) than for the
foot treated with vehicle (61.9  29.7 mm; P = 0.022). Subjects
confirmed their preference for using the emollient rather than
the vehicle, both at D14 (VAS: 74.7  27.0 mm vs.
63.1  34.5 mm; P = 0.049) and at D28 (72.6  26.4 mm vs.
59.4  32.0 mm; P = 0.015).
Safety
Seventeen adverse events (11 mild, three moderate, three severe)
were reported by 23.2% of the study population, including two
local-regional adverse events reported by two subjects: mild
intensity cracks on the foot treated with the emollient cream.
One case of interdigital maceration and crack was judged by the
investigator as being probably related to the study treatment.
For the other 16 adverse events, there was no relationship to
study treatment. Three serious adverse events occurred before
the initiation of study treatment.
Discussion
Foot care in diabetic patients is challenging to prevent complica-
tions. The first step is to maintain good skin hydration and to
reduce xerosis and hyperkeratosis.14
Symptoms in diabetic foot can be graded from xerosis with
flakes, to scales and then fissures, with the latter being a key
symptom before major complications. Pham et al.3 specifically
developed the XAS score, a nine-grade scoring system, for evalu-
ating cutaneous symptoms in diabetic foot.
The current randomized, vehicle-controlled study shows that
the regular use of an emollient significantly improves xerosis
after 28 days of treatment. The emollient group showed a better
improvement in xerosis (mean XAS score 3.2  2.6, corre-
sponding to a limited number of scales) than the vehicle group
(mean XAS score: 4.1  2.3, corresponding to a moderate num-
ber of scales). The 0.9-point difference in XAS score with the
emollient versus the vehicle (P = 0.001) surpassed the planned
0.8-point difference and was of clinical relevance considering
that patients were required to present with an XAS score of 46

JEADV 2016 2016 European Academy of Dermatology and Venereology

Emollient cream improves xerosis in diabetic foot
at baseline. The clinical improvement was also confirmed by
instrumental measurements (D-Squame, corneometer and skin
relief), with a hydration effect that was significantly better for
the emollient compared to the vehicle from D14, a regularization
of the desquamation process and a decrease in skin roughness
over time (Fig. 3). These outcomes demonstrate the effectiveness
of the moisturizing activity of the test product and its properties
to improve skin hydration.
The use of a true placebo in clinical studies with topical
treatment can be challenging, especially for cutaneous xero-
sis, because any cream applied to the skin can show some
moisturizing action. As we used the emollient vehicle as the
control (which itself could have some emollient and hydrat-
ing effects), this study highlights the specific effect of the
active compounds (glycerol, paraffin) included in the test
emollient to promote and restore skin hydration. However,
these results observed at 4 weeks of treatment do not pre-
dict the efficacy of the emollient cream over a longer treat-
ment duration, particularly when hyperkeratosis becomes
important again and, as such, study duration represents a
potential limitation.
In summary, the objective of this study was to evaluate
the effectiveness and safety of an emollient cream versus its
vehicle on foot xerosis after 27  2 days of treatment in a
diabetic population. Compared with the vehicle, the emol-
lient significantly decreased foot skin dryness, according to
subjective (XAS and overall skin scores) and instrumental
(corneometer, D-Squame, skin relief) measurements. More-
over, the emollient demonstrated a good safety profile. In
conclusion, emollients are an effective treatment for xerosis
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5
of the foot in patients with diabetes and can, therefore, be
considered as part of the therapeutic management of such
disorders.
Acknowledgements
The authors thank David P. Figgitt PhD, Content Ed Net, for
providing editorial assistance in the preparation of the manu-
script, with funding from Pierre Fabre Dermatology, Lavaur,
France.
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2016 European Academy of Dermatology and Venereology