Piroctone Olamine 0.8% Shampoo
Piroctone Olamine 0.8% Shampoo
Piroctone Olamine 0.8% Shampoo
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DOI: 10.1111/ics.12737
ORIGINAL ARTICLE
1
The Procter & Gamble Company,
Mason, Ohio, USA Abstract
2
Department of Dermatology, Objective: Increasing scalp hair fullness is a global unmet consumer need. An
Cleveland Clinic, Cleveland, Ohio, USA approach to decrease hair shedding by reducing scalp stratum corneum oxidation
3
Department of Pathology, Cleveland via a combination of antioxidant and barrier-enhancing technologies has been
Clinic, Cleveland, Ohio, USA
4
previously demonstrated. The purpose of this study was to test the effectiveness
The Procter & Gamble Company,
Singapore, Singapore of the individual antioxidant piroctone olamine in two different product forms
Correspondence
(shampoo or leave-on product) for activity to improve hair retention.
Michael G. Davis, The Procter & Methods: Female subjects with self-perceived hair thinning participated in an
Gamble Company, Mason, Ohio, USA. 8-week, double-blind, placebo-controlled, randomized clinical study to evaluate
Email: [email protected]
either a piroctone olamine (PO) containing shampoo or a PO containing leave on
Funding information treatment, each relative to their corresponding placebo formulation Too many
P&G Beauty
periods. Results for phototrichograms, TEWL, and biomarker analysis of scalp
condition for the shampoo treatments are discussed. Phototrichogram results are
shared for the assessment of the leave on treatment.
Results: Statistically significant increases in hair amount were observed by pho-
totrichogram after use of both PO-containing products versus placebo formula-
tions. The PO shampoo treatment also significantly decreased oxidative stress on
the hair and scalp, and improved scalp condition as assessed by TEWL and scalp
biomarker values.
Conclusion: These results illustrate the effectiveness of a cosmetic antioxidant
to improve scalp condition thereby improving hair retention. The observed im-
provements in scalp condition are consistent with previous reports with other
antioxidant technologies and suggest that the hair retention effect was achieved
by preventing oxidative damage to the scalp.
KEYWORDS
antioxidant, hair growth, hair loss, hair shedding, hair treatment, scalp, skin barrier
26 | wileyonlinelibrary.com/journal/ics
Int J Cosmet Sci. 2021;43(Suppl. 1):26–33.
DAVIS et al. | 27
T A B L E 1 Compositions of treatment
Treatment Leave-on
formulations
Function Materials (all USP grade) shampoo treatment
Surfactants Sodium laureth sulphate Xa
Sodium C10-15 pareth sulphate X
Cocamide MEA X
Hair/skin Bis-aminopropyl dimethicone X
conditioners Glycerine X
Bis-PEG / PPG-16/16 PEG / X
PPG16/16 dimethicone
Thickeners Acrylates/C10-30 alkyl acrylate X
crosspolymer X
Acrylates copolymer
Stabilizer Glycol distearate X
Solvents Water X X
SD alcohol 40-B X
Deposition aid Guar hydroxypropyltrimonium X
chloride
Cosmetic Piroctone olamineb 0.8% 0.45%
functional
ingredient
a
X denotes present in the formulation; specific levels are proprietary.
b
Not included in placebo control products.
28 | PIROCTONE OLAMINE DECREASES HAIR SHEDDING
the Cleveland Clinic visited the test facility to observe all hundred and forty-four subjects finished the study (71 in
study procedures to verify adherence to the protocol. The the placebo group and 73 in the treatment group). Subjects
studies were conducted from April to June 2019. were also resupplied with a commercial conditioner along
with test formulations with instructions to apply only to
the last few inches of hair and avoid direct application to
Study design and subjects the scalp. Subjects were instructed to use only the supplied
products provided for the entire study period: shampoo 4
These were randomized, double- blind studies among times per week and conditioner ad lib only at the tips of the
healthy female subjects (ages 25–65) with Fitzpatrick skin hair. Subjects were provided enough products and formula-
type I-IV [8] who had self-perceived thinning hair to eval- tions for 2 months of typical usage. All products and for-
uate the effectiveness of either a shampoo treatment or a mulations were stored at room temperature. Measurements
leave-on treatment relative to their corresponding placebo were taken at baseline and after 8 weeks of treatment.
formulations. Scalp redness was evaluated by a trained
grader at baseline. Any subject with a grade of 2.0 or
higher (on a 6-point scale) was dismissed from participa- Study design and sample size for
tion in the study. Protocol deviations were recorded to de- assessment of the leave-on treatments
termine which subjects, endpoints and timepoints should
be excluded from subsequent data analysis. This was a left-right, split-scalp comparison of a leave-on
Subjects were instructed (verbally and in writing) re- 0.45% piroctone olamine treatment formulation applied
garding proper use of the test products and formulations. to one side of the scalp vs. a placebo leave-on formula-
Subjects also kept a diary of their product usage. Product tion without cosmetic functional ingredients applied to
containers were weighed as a measure of product usage. the other side of the scalp (Table 1). The remaining 43 of
All subjects were supplied the same commercial sham- the enrolled subjects were placed in this treatment study.
poo and conditioner products to use 4 times per week in a That number was determined to provide 80% power to
2-week washout phase. After the washout phase, 189 sub- detect differences in the phototrichogram measurement.
jects were enrolled into the studies. Since this was a split-scalp design, the side of the scalp
During the treatment phase, subjects were permitted to receiving treatment was randomized. All enrolled subjects
colour or trim their hair within one week after a clinical were supplied a commercial shampoo and conditioner to
site visit, but they could not change hair style for the dura- use during the treatment phase and were coached in 1-
tion of study, nor have any salon procedures such as per- on-1 supervised sessions on proper procedure for formula-
manent waves, chemical relaxing or straightening. They tion application at baseline and at a 4-week return visit to
were instructed to avoid sun exposure on the scalp and the clinical site. Subjects applied 7 pumps (~1.5 g) of prod-
could not use other leave-on hair treatments. No other re- uct from the supplied pump container and rubbed it into
strictions were applied. the entire half scalp once per day. Measurements were
taken at baseline and after 8 weeks of treatment. Forty-
two subjects completed the study.
Study design and sample size for
assessment of the shampoo treatments
Study procedures
Assuming 80% power to detect a statistically significant
difference in hair count by phototrichogram and allow- The study procedures are described in the companion
ing for drop rate, 146 of the enrolled subjects were rand- manuscript [2] and are summarized here. Hair measure-
omized to either the treatment shampoo or a placebo ments were done at baseline and after 8 weeks of test for-
shampoo. Randomization balanced for the following hair mulation usage. Measurements for subjects treated with
loss and scalp health baseline factors: number of shed hairs shampoo included phototrichogram, trans- epidermal
collected during screening (low, medium, high), a derma- water loss (TEWL) measurements and tape strips for
tologist assessment of hair loss (Ludwig grade I-1, I-2, I-3), biomarker assessments. For the subjects on the leave-on
Adherent Scalp Flaking Score [9] as judged by a qualified treatment, phototrichogram assessment was performed.
grader on 8 regions of the scalp and age (25–40, 41–49, 50– All phototrichogram analysis was performed using the
65). Subjects were randomized to one of two groups: whole automated AI algorithm previously described [2, 10]. The
head treatment shampoo formulation containing 0.8% pi- details of the measurements follow.
roctone olamine or identical whole head placebo shampoo Two days prior to each clinical site visit and evaluation,
formulation that lacked piroctone olamine (Table 1). One subjects were instructed to shampoo their hair with the
DAVIS et al. | 29
provided shampoo, apply conditioner ad lib only to the the remaining short hairs within the clipped areas were
tips of their hair, rinse off the conditioner and refrain from cut to approximately 0.5 mm in length using a #2041
using any hair care or styling implements until after their Doodle Blade® attached to a corded Wahl® hair clipper
clinical site visit. Subjects were also instructed to refrain (Wahl Home Products) in preparation for imaging. At
from consuming any foods or beverages containing caf- subsequent visits, short regrowth hairs in the clipped
feine or to use nicotine products for 2 h prior to a clinical areas were cut from the scalp with scissors before being
site visit. trimmed as above before imaging.
For biomarker analysis, the skin samples on tape strips A Canfield VEOS Macro Imaging System (Canfield
were analysed as reported previously [11]. Scientific) was used to capture images of the left and
Hair measurements were done at baseline and site right scalp clipped areas, using the scalp tattoos and
visits after 8 weeks of product. At all timepoints, visits the imaging system contact plate to reposition the cam-
were comprised of 2 sequential days in order to prop- era to the same scalp area, angle and distance for each
erly sequence the measurements to minimize manipula- time point. A trained operator used the imaging sys-
tions for the subjects and undue measurement artefacts. tem. Hair counts were analysed with a novel machine-
Measurements included Canfield macro imaging, self- learning algorithm for counting hairs [10]. This method
assessment questionnaire, TEWL in a controlled tem- was qualified with data from previous hair quantifica-
perature and controlled humidity (CTCH room) and tape tion studies.
strips. The details of those measurements follow. Outside of the clipped areas, 5 tape strip locations were
Hair baseline shedding quantitation: A novel method selected on either side of the head corresponding to the
for hair shedding analysis was developed for this study treatment site for each side. The first started 1” from the
and was executed as follows: in a controlled temperature frontal hairline, and each successive tape strip location
and controlled humidity, a study Cosmetologist removed was next to the prior tape strip location moving towards
the hair from the ponytail, while the subject was seated in the back of the head. The adjacent, non-overlapping tape
a massage chair, with the subject's head positioned over a strip sites did not extend into the clipped areas. Two strips
collection box to capture any loosened hairs from the po- with D-Squame® tape (CuDerm Corp., 22-mm discs, D-
nytail fall. Using the coarse teeth of a Conair Detangle & 100) were done at each of the five sites. Any adhering
Style comb (Style Comb #935022, Conair Corp.), hair was hairs were removed with tweezers. The strips were frozen
gently detangled. Then, the hair was combed with the fine until assayed for skin biomarkers.
teeth for 100 strokes downwards into the collection box,
combing all hairs on the entire scalp. Shed hairs were col-
lected on Cling VinylTM sheets (Creative-Coldsnow.com), Statistics
which were subsequently stained with rhodamine B dye
(Sigma-Aldrich) to highlight the shed telogen hair bulbs All statistical analysis followed ICH- E9 Statistical
[12]. The hairs were counted manually, twice by each Principles for Clinical Trials. For all endpoints, treat-
of 3 separate qualified graders. Each grading session in- ment effects were assessed for the measured response (or
cluded control standards inserted randomly for validating a transformation of it) with the analysis of covariance to
the grading accuracy. Broken hair fibres were not counted adjust for the baseline response level. For the split-scalp
in the hair shedding analysis. portion, a mixed model was used since the subject is the
For relocating the same sites on the scalp for each experimental/statistical unit.
visit, a small site (1.9 × 1.9 cm) to be clipped was se-
lected on the left and right sides of the centre of the
scalp (directly above the ears) by a licensed cosmetolo- RESULTS
gist. A licensed tattoo artist then made a small tattoo dot
to mark each site. At baseline, there were no significant differences between
Within the clipped areas, the hairs were drawn into control and treatment groups. At baseline, the average
a bundle and secured with tape. The bundled hairs were total Adherent Scalp Flaking Score (ASFS) was 7.2, con-
then clipped with scissors as close as possible to the sidered asymptomatic/non-flaking scalp [9]. All subjects
scalp. The long hairs were pinned away from the clipped were classified as having minimal clinical signs of hair
sites to expose the scalp to ambient conditions during loss.
the 20-min acclimation period in a CTCH room prior Biomarker analysis after 8 weeks of shampoo treat-
to taking trans-epidermal water loss (TEWL) measure- ment is summarized in Figure 1a-e. S100A12 is a common
ments of the clipped sites (AquaFluxTM AF-200 TEWL biomarker of many non- optimal skin conditions [13].
Towson). Following completion of TEWL measurements, Treatment with the PO shampoo significantly reduced
30 | PIROCTONE OLAMINE DECREASES HAIR SHEDDING
the level of S100A12 in tape strips versus the placebo shampoo (Figure 1e). A lower TEWL indicates improved
shampoo (p = 0.0013) (Figure 1a). The PO shampoo also barrier and better scalp condition.
significantly reduced oxidative stress biomarker myelop- Analysis of hydroxyoctadecadienoic acid (HODE), an
eroxidase (MPO) (p = 0.0082; Figure 1b). HODE (hy- oxidation product of linoleic acid and marker of hair shaft
droxyoctadecadienoic acid) is an oxidation product of oxidative damage, showed a significant reduction for the
linoleic acid and is thus a marker of scalp oxidative stress PO shampoo versus the placebo shampoo (p = 0.0136) at
status. HODE measured from scalp tape strips was statis- week 8 (Figure 2).
tically significantly reduced (p ≤ 0.0025) in subjects using
the hair treatment regimen versus the placebo shampoo
after 8 weeks of treatment (Figure 1c). For human serum Total hair counts
albumin (HSA), a marker of skin barrier function, the PO
shampoo showed a directional effect (p = 0.0822) versus Phototrichogram images within the scalp hair- clipped
the placebo shampoo (Figure 1d). While this observation areas were analysed by an in- house automated algo-
is not statistically significant, the numerical effect is con- rithm [1, 10]. Total hair counts were greater in sub-
sistent with the TEWL data (i.e. improved barrier func- jects using the piroctone olamine (PO) shampoo versus
tion). The PO shampoo showed a statistically significant those using the placebo shampoo (Figure 3a). After only
(p = 0.0477) decrease in scalp TEWL versus the placebo 8 weeks of product usage, the PO shampoo showed a
DAVIS et al. | 31
DI S C US S I O N
F I G U R E 3 Quantification of hair counts by the
As mentioned in the introduction, once hair is lost, there phototrichogram machine learning algorithm method after 8 weeks
are few non-surgical reliable options to re-grow it [1]. Our of the PO test product usage versus the corresponding placebo
hypothesis [2, 3] is that premature hair loss is due to non- product. The specific p value is indicated in the text. (# significant
optimal scalp condition resulting in an environment that is from placebo). (a) Phototrichogram hair counts after 8 weeks of
not maximally supportive of normal hair fibre maturation PO shampoo (SH) usage. (b) Phototrichogram hair counts after
and retention. The cause-and-effect association between 8 weeks of PO containing leave-on treatment (LOT) usage
scalp condition and maturation of pre-emergent hair fibre
is well established based on epidemiological and treat-
ment studies of compromised scalp conditions with spe- Piroctone olamine (PO) is a well-known treatment for
cific symptomologies [3]. It is likely that these disturbed improving scalp condition (reduction of dandruff) [20].
scalp conditions create an environment that perturbs nor- Additionally, previous reports demonstrate that (PO) is
mal fibre maturation during the near two-week transit to also a metal chelator [21]. Metals, such as iron, can con-
the scalp surface impairing optimal fibre anchorage. tribute to the progression of adverse reactions such as the
The means of transmission of a compromised scalp to formation of hydroxyl radicals and metal chelators have
the nascent hair fibre are likely oxidative stress. All the been shown to prevent iron-catalysed oxidative damage
disrupted scalp conditions studied that have shown detri- [22–25]. As discussed in the companion work to this
mental impacts to the associated hair have oxidative stress manuscript [2], oxidation of stratum corneum can result
as a common etiological element [14]. Additionally, it is in damage to the scalp skin barrier via multiple mech-
widely accepted that normal human ageing is also a con- anisms and thus lead to more complex problems that
sequence of a progression of oxidative stress [15, 16]. The can result in premature hair loss and shedding. Since PO
sources and consequences of oxidative stress with respect was effective in improving the measures of these prob-
to the hair are well documented [11, 17–19]. lems (i.e. TEWL and skin biomarkers), this antioxidant
32 | PIROCTONE OLAMINE DECREASES HAIR SHEDDING
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expression by iron chelators in neuroblastoma cells. Mol.
Pharmacol. 87, 513–524 (2015).
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Photobiol. 64, 918–922 (1996). piroctone olamine reduces hair shedding in an
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