Clln Drug Invest 2009; 29 (5); 283-292
117 3-2563/09/0C05-0283/S49.95/0

ORIGINAL RESEARCH ARTICLE© 2CXJ9 Adls Data Information BV. All rights reserved.

HairMax LaserComb® Laser
Phototherapy Device in the Treatmentof Male Androgenetic Alopecia
A Randomized, Double-Blind, Sham Device-Controlled,
Multicentre Trial
Matt Leavitt} Glenn Charles/ Eugene Heyman 3 and David Michaels 4
1 Private Dermatology Practice, Maitland, Florida, USA
2 Private Hair Transplantation and Restoration Practice, Boca Raton, Florida, USA
3 Biostatistician, Montgomery Village, Maryland, USA
4 Lexington International, LLC, Boca Raton, Florida, USA

Abstract

Background and objective: The use of low levels of visible or near infrared lightfor reducing pain, inflammation and oedema, promoting healing of wounds,
deeper tissue and nerves, and preventing tissue damage has been known foralmost 40 years since the invention of lasers. The Hair Max LaserComb® is a
hand-held Class 3R lower level laser therapy device that contains a single laser
module that emulates 9 beams at a wavelength of 655 nm (±5%). The device uses
a technique of parting the user's hair by combs that are attached to the device. This
improves delivery of distributed laser light to the scalp . The comb are designedo that each of the teeth on the combs aligns with a laser beam. By aligning theteeth with the laser beams, the hair can be parted and the laser energy delivered tothe calp of the user without obstruction by the individual hairs on the scalp. The
primary aim of the tudy was to asses the afety and effectiveness of the HairMax
La erComb® laser phototherapy device in the promotion of hair growth and in the
cessation of hair loss in males diagnosed with androgenetic alopecia (AGA).
Methods: This double-blind , sham device-controlled, multicentre, 26-week trial
randomized male patients with Norwood-Hamilton classes Ila-V AGA to treatment with the HairMax LaserComb® or the sham device (2: 1). The sham deviceu ed in the study was identical to the active device except that the laser light was
replaced by a non-active incandescent light source.
Results: Of the 110 patients who completed the study, subjects in the HairMax
LaserComb® treatment group exhibited a signilicantly greater increase in meanterminal hair density than subjects in the sham device group (p < 0.0001).
Consi tent with this evidence for primary effectiveness, ignificant improvementsin overall hair regrowth were demon trated in terms of patients' subjective
as essment (p < 0.015) at 26 week over ba eline. The HairMax LaserComb® waswell tolerated with no serious adverse events reported a nd no tati tical differencein adverse effects between the study groups.

284

Leavitt et al.

Conclusions: The results of this study suggest that the HairMax LaserComb® isan effective, well tolerated and safe laser phototherapy device for the treatment of
AGA in males.

Background
Laser phototherapy i a popular therapeutic modality that relies on exposure of biological tissues tolow power coherent monochromatic light;Pl this induce a variety of positive therapeutic benefits associated with a range of wavelengths from red throughto infrared. Pioneer studies on laser biostimulation
performed more than 40 years ago reported a prominent hair growth stimulatory effect in mice.l21 In
recent years, considerable attention has been given
to establishing a regeneration-promoting effect oflaser phototherapy in wound healing and tendon,muscle,[31fractured bone[4 ,5J and skin.l6l Most prominently, several recent studies have confirmed thetimulatory effect of laser phototherapy on cutaneous wound regeneration (i.e. wound healing)_(6-IOJ
Stimulation of proliferation was found to be at least
one of the mechanisms underlying the pro-regenerative effect of laser phototherapy[ 11 - 131Because both
reparative regeneration, which occurs during woundhealing, and physiological regeneration, which occurs during the hair cycle, rely heavily on cell proliferation, it is plausible to suggest that the hair
growth stimulatory effect of laser phototherapy isalso mediated through either a direct or an indirect
increase in proliferative activity within the hair follicle epithelial matrix.
The basis of the biostimulatory effect of laser
phototherapy during wound healing is not fully understood. As noted a bove, at the cellular level, laser
phototherapy has been shown to increase proliferation of fibroblastsP 1- 131 including fibroblasts derived from streptozotocin-diabetic rats that otherwise exhibit impaired proliferative activity.l 141 Several intracellular proce ses are believed to underlie
this pro-proliferative effect, including short-term activation of the mitochondrial electron-transport
chain, accumulation of intracellular adenosine triphosphate and alkalization of the cytoplasm.PI ,IS]
Because laser phototherapy-promoted wound healtel 2009 Adis Data Information BV. All rights reserved .

ing is also characterized by faster wound re-epithelialization and neovascularization,[ 141direct enhancement of epidermal and endothelial proliferation in
wound sites is plausible. In addition, the proproliferative action of laser phototherapy can be
attributed to other indirect effects, one of which is a'metabolic boost' of the regenerating ti ues
through increased cutaneous microcirculation that
occurs upon laser irradiation.P 61Another effect islinked to stimulated secretion of endogenous growth
factors, such as basic fibroblast growth factor andinsulin-like growth factor-!, by fibrobla ts exposedto laser phototherapy.[I7J Both of these growth factors are potent natural stimulators of proliferation
for a variety of cell types.P71
Hair is one of the fastest growing tissues of thehuman body. Hair follicles undergo repetitive physiological regenerative cycles,P 81 and each such cycle
consists of three principal phases: telogen (resting
phase), anagen (active phase) and catagen (physiological involution phase). At the basis of this hair
growth cycle are two major processes. The first
represents tightly controlled activation of epithelial
bulge stem cells and econdary hair germ cells thatgive rise to transient amplifying (TA) progeny cells
during telogen-to-anagen transition.P 91 The second
process constitutes robust proliferation of the e T A
cells within the epithelial matrix of the hair follicle
throughout the entire length of anagen. Proliferation
trichocytes terminally differentiate to form the bulkof the hair filament- the final product of the haircycle. The dermal papilla of the hair follicle isbelieved to play a key regulatory role in orchestrating the above described processes of progenitor cell
activation, hair matrix cell proliferation and terminal
differentiation of trichocytes_[201Androgenetic alopecia (AGA) is one of the mostcommon forms of hair loss in males and females.[2 11In genetically predisposed scalp hair follicles,
dihydrotestosterone- a potent derivative of the maleClin Drug Inve st 2009; '29 (5)285HairMax LaserComb® Laser Phototherapy in Male Androgenetic Alopecia

sex hormone testosterone - initiates the cascade ofdownstream signalling changes beginning in thedermal papillae fibroblasts that ultimately disturb
normal metabolic and cellular dynamics of the entire
follicle. [22l As a result, a marked reduction inproliferative activity in the hair follicle epithelium
leads to morphological miniaturization of terminal
scalp hairs into vellus-like hairs.l23l Furthermore, abroken mechanism of bulge stern cell and secondary
hair germ cell activation prevents new anagen reentry, converting cycling hair follicles into quiescent telogen follicles. Thus, while the aetiologicalbasis of AGA is clearly in abnormal androgen signalling, disruption of epithelial progenitor cell activation and T A cell proliferation forms an essential
pathophysiological component of this conditionP3l
Since laser phototherapy has pro-proliferative effects in a variety of tissues and cell types, we hypothesized that it might have similar pro-proliferative activity in hair follicles and might normalize
physiological regeneration of scalp hair follicles
affected in AGA. The phenomenon of so-called'terminalization' of vellus human hair follicles (i.e.
when small vellus hairs transform into larger, terminal hairs) upon low fluence diode laser treatment has
been independently reported by two researchers. [24,251
To further evaluate the validity of our as urnptions, we measured the hair growth-promoting efficacy of the HairMax LaserComb® laser phototherapy device in a randomized, double-blind, sham device-controlled, rnulticentre trial in male patientswith AGA. The HairMax LaserCornb® is a handheld Class 3R lower level Ia er therapy device that
contains a single laser module that emulates 9 beams
at a wavelength of 655 nrn (±5%). From past 'inuse' experience with the first devices it was foundthat there is a so-called 'optical window' for lower
level light (LLL) in skin. LLL in skin appears to beeffective in red and near-infared spectrum (600-950nm) and the Hair Max LaserComb® was found to be
optimally effective at a wavelength of 655 nm(±5%).[261 The device uses a technique of parting theuser's hair by combs that are attached to the device.
This improves delivery of distributed laser light to© 2009 Adis Data Info rmation BV. All rights reserved.

the scalp. The combs are designed o that each of theteeth on the combs aligns with a laser beam. Byaligning the teeth with the laser beams, the hair canbe parted and the laser energy delivered to the scalpof the user without obstruction by the individual
hairs on the scalp. Here we report on the outcome ofthis trial.
Methods
This clinical study was performed in accordancewith Good Clinical Practice. The protocol was approved by the Investigational Review Board, Research Testing Laboratories Inc., Great Neck, NY,
USA, and written informed consent was obtained
from each patient in the study before study procedures were conducted.
Study Objectives

The primary aim of the study was to assess
the safety and effectiveness of the HairMax
LaserCornb® laser phototherapy device in the promotion of hair growth and in the cessation of hairloss in males diagnosed with AGA. Nter the study
began it was amended to include only males at thesuggestion of the US FDA; female subjects will
form the basis of a similar study.
Study Inclusion/Exclusion Criteria

For inclusion in the study, subjects must not haveused or taken any of the following medications for6 months prior to initiation of the study: rninoxidil,
finasteride (or any other Sex-reductase inhibitor
medications), medications with anti-androgenic
properties (e.g. cyproterone, spironolactone, ketoconazole, flutarnide and bicalutarnide), topical estrogens, progesterone, tarnoxifen, anabolic steroids,
medications that can potentially cause hypertrichosis (e.g. ciclosporin, diazoxide, phenytoin andpsoralens), oral glucocorticoids (inhaled glucocorticoids were permitted), lithium, phenothiazines orother medications at the discretion of the investigator. Subjects were excluded if they had had hairtransplantation, scalp reduction, current hair weave
or tattooing of the alopecic area, which would havemade for difficulties in performing objective hair
Clin Drug Invest 2009; 29 (5)286

Leavitt et al.

density asses ments. Subjects were also excluded ifthey had any known underlying medical conditions
that could adversely affect hair growth, such as HIV
infection, connective tissue disease, inflammatory
bowel disease, or other pathologies at the discretionof the investigator.
Patient Population

The study population included males between theages of 30 and 60 years with a diagnosis of AGA
who had been experiencing progre sive hair loss
within the last 12 months. Subjects were also required to have a Norwood-Hamilton male patternhair loss classification of IIa to V and to have skin
type I to IV on the Fitzpatrick Skin Type Scale.
Study Design

The study was designed as a randomized, doubleblind, sham device-controlled, multicentre trial conducted at four sites in the US. Subjects who met
all entry criteria received either the HairMax
LaserComb®, which emitted laser light, or a shamdevice, which was identical to the active device inappearance but emitted incandescent light instead.
Screened subjects who fulfilled study entry criteria attended a ba eline visit. At this visit, medical
personnel assessed the subject's scalp for any signsof irritation or dermatological conditions that would
disqualify the subject from participation. All subjects had systolic and diastolic blood pressure(mmHg) and heart rate (beats/min) vital signs recorded. Scalp macroimages utilizing dot mappingand computer-aided hair counts (see Evaluation ofClinical Efficacy section) were taken to document
hair loss progression since the screening visit. Eachtarget site for investigation was chosen by the clinical investigator based on the appearance of miniaturized hairs, which are the hallmark of AGA. Target scalp areas were identified and tattooed, thenclipped to determine baseline hair density. Subjects
were then provided with their randomized HairMax
LaserComb® or sham device (see Statistical Analysis section for randomization scheme). In previous'in-use' studies utilizing various application regimens to find the effective minimum dose of the© 2009 Ad is Data Information BV. All rights reserved.

HairMax LaserComb®, it was found that applicationof the device three times a week was sufficient to
induce hair growth.[26l Therefore, subjects wereasked in the current study to use the device assigned
three times per week for 15 minutes on non-concurrent days for a total of26 weeks/6 months. Subjects
were given diaries to document use of the device.
Subjects returned to the clinic at 8 and 16 weeks
to undergo assessment for adverse events and concomitant medications, collection of vital signs, scalp
evaluation for local dermatitis and other pathological conditions, and completion of an 11-item questionnaire. Clinical assessment of treated scalp sites
was carried out objectively at 26 weeks/6 months
utilizing macroimaging techniques, hair clippings,
computer-aided hair counts (see Evaluation of Clinical Efficacy section) and global assessment of
new hair growth (i.e. without referring to any
macroimages) by subjects and the investigator. Subjects who terminated prematurely had their hair density measured at their termination visit.
The evaluator of the baseline and endpoint analyses of the macroimages used blinded patient files
and was not involved in patient selection or distribution of either device. The cut-off time for use of thedevice was 6 months. At the completion of thestudy, all subjects in each arm of the study were
offered a HairMax LaserComb® for their personaluse.
No post-study follow-up was conducted.
Evaluation of Clinical Efficacy
Hair Clipping

A circle of approximately 2.96cm diameter,
positioned in the vertex portion of the scalp, wasidentified as the site for hair clipping. This site
contained some miniaturized hairs and was the target area for the hair density evaluation. A template
was provided to the investigator for identifying thearea for hair clipping. Once the hair had beenclipped, trained study personnel used a professional
tattooing machine to apply a permanent ink dot,
approximately the size of a full stop/period(.), in thecentre of the circle. The tattoo was used as a guidefor placing the template on the scalp surface atClin Drug Invest 2009: 29 (5)HairMax LaserComb® Laser Phototherapy in Male Androgenetic Alopecia

ubsequent visits for the hair clipping andmacroimages for hair density evaluation.
Macroimaging and Hair Density
Evaluation Procedures

Macroimage Acquisition

The subject sat in a chair and was correctly
placed in the stereotactic apparatus. The digital
images were standardized for lighting, camera angle
and po ition of the subject's head in each digital
image to achieve a similar camera angle and relative
image size. For macrodigital images a template as
described in the previous section was placed on thelenses for precise and consistent alignment on the
tattoo. A I 0 mm scale divided into 0.1 mm increments was etched into the template for calibration
purposes during the hair density evaluations. The
images were recorded on compact flash cards.
During the subject's visit, the images werepreviewed to ee if they were acceptable; unacceptable images were retaken. After the subject's visit
had been completed, the images were printed andsigned by the investigator and uploaded to a de ignated ite for image archiving.
Image Analysis and Management

A state-of-the art software system was utilized
for image management Macroimage were imported into a blinded subject file labelled by subject
number. The images displayed included a means ofmarking each individual hair. Each hair was 'clicked' and a running count was displayed at the bottomof the software window. Only terminal hairs werecounted. Archives of the counted hairs were maintained in the subject file. Images could be displayedside by ide.
The database software functionality also allowed
subjects to be identified by number while the advanced multiple criteria searches facilitated quick
retrieval of information. In addition, the ubject's
chart view allowed all of a subject's images to beviewed on one screen with scalable thumbnails.
Blinded ubject record containing hair density
measurement were forwarded to data management
for inclusion in the tudy data base.
@ 2009 Adis Data Informa tion BY. All rights reserved.

287

Study Endpoints

The primary efficacy endpoint was change in
non-vellus terminal hair density (hairs/cm 2) in thetarget region between baseline and endpoint (26weeks/6 months or the earlier termination visit), as
assessed by scalp macroimaging using dot mappingand computer-aided hair counts (see Evaluation ofClinical Efficacy section). The techniques used werecomparable to those used in the protocols for minoxidil.
Secondary effectiveness endpoints were subjective global assessment of hair regrowth by subjects
and the investigator at week 26. Patients were a ked
to complete the !!-question proprietary Subject
Questionnaire without assistance, aimed at evaluating perception of overall hair regrowth characteristics. These questions encompassed overall re ults,
rate of hair loss, assessment of dandruff, scalp
health, hair health, hair thickness, hair shine, hair
growth rate, manageability and hair colour change .
Investigators were asked to evaluate the ubject's
hair growth looking at the baseline and week 26/6
months (or early termination) visit global images(without reference to macroimages) and graded thehair growth on a 4-point scale.
The safety endpoints for the study were adverse
events of any nature and vital signs.
Statistical Analysis

Based on prior data for the HairMax
LaserComb®[26l and the drug minoxidil (NDA20-834, Pharmacia and Upjohn Consumer Healthcare, November 14, 1999) the standard deviation ofchange from baseline in terminal hair density was
assumed to be 30 hairs/cm2 . Based on this estimate,
93 subjects randomized 2: I (62 in the HairMax
LaserComb® group and 31 in the sham device
group) would provide 85% power to detect a difference of 20 hairs/cm 2 To allow for a 20% dropout
rate, 123 subject needed to be enrolled. Stati ticalcomparisons were made between treatment groupfor all baseline demographic variables. Continuous
variable were compared using two-sample t-tests:
dichotomou variables were compared using Pearson's chi- quared test (x 2) and ordinal variables by
Clin Drug Invest 2009: 2Q (5)286

Leavitt et a/.

density assessments. Subjects were also excluded ifthey had any known underlying medical conditions
that could adversely affect hair growth, such as HIV
infection, connective tissue di ease, inflammatory
bowel disease, or other pathologies at the discretionof the investigator.
Patient Population

The study population included males between theages of 30 and 60 years with a diagnosis of AGA
who had been experiencing progressive hair loss
within the last 12 months. Subjects were also required to have a Norwood-Hamilton male patternhair loss classification of Ila to V and to have skin
type I to IV on the Fitzpatrick Skin Type Scale.
Study Design

The study was designed as a randomized, doubleblind, sham device-controlled, multicentre trial conducted at four sites in the US. Subjects who met
all entry criteria received either the HairMax
LaserComb®, which emitted laser light, or a shamdevice, which was identical to the active device inappearance but emitted incandescent light instead.
Screened subjects who fulfilled study entry criteria attended a ba eline visit. At this visit, medical
personnel assessed the subject's scalp for any signsof irritation or dermatological conditions that would
disqualify the subject from participation. All subjects had systolic and diastolic blood pressure(mmHg) and heart rate (beats/min) vital signs recorded. Scalp macroirnages utilizing dot mappingand computer-aided hair counts (see Evaluation ofClinical Efficacy section) were taken to document
hair loss progression since the screening visit. Eachtarget site for investigation was chosen by the clinical investigator based on the appearance of miniaturized hairs, which are the hallmark of AGA. Target scalp areas were identified and tattooed, thenclipped to determine baseline hair density. Subjects
were then provided with their randomized Hair Max
LaserComb® or sham device (see Statistical Analysis section for randomization scheme). In previous'in-use' studies utilizing various application regimens to find the effective minimum dose of the@ 2fXfl Adis Data Info rmation BV. All rights reseNed .

HairMax LaserComb®, it was found that applicationof the device three times a week was sufficient to
induce hair growth.l26l Therefore, subjects wereasked in the current study to use the device assigned
three times per week for 15 minutes on non-concurrent days for a total of26 weeks/6 months. Subjects
were given diaries to document use of the device.
Subjects returned to the clinic at 8 and 16 weeks
to undergo assessment for adverse events and concomitant medications, collection of vital signs, scalp
evaluation for local dermatitis and other pathological conditions, and completion of an 11-item quetionnaire. Clinical assessment of treated scalp sites
was carried out objectively at 26 weeks/6 months
utilizing macroirnaging techniques, hair clippings,
computer-aided hair counts (see Evaluation of Clinical Efficacy section) and global assessment of
new hair growth (i.e. without referring to any
macroimages) by subjects and the investigator. Subjects who terminated prematurely had their hair density measured at their termination visit.
The evaluator of the baseline and endpoint analyses of the macroirnages used blinded patient files
and was not involved in patient selection or distribution of either device. The cut-off time for use of thedevice was 6 months. At the completion of thestudy, all subjects in each arm of the study were
offered a HairMax LaserComb® for their personaluse.
No post-study follow-up was conducted.
Evaluation of Clinical Efficacy
Hair Clipping

A circle of approximately 2.96cm diameter,
positioned in the vertex portion of the scalp, wasidentified as the site for hair clipping. This site
contained some miniaturized hairs and was the target area for the hair density evaluation. A template
was provided to the investigator for identifying thearea for hair clipping. Once the hair had beenclipped, trained study personnel used a professional
tattooing machine to apply a permanent ink dot,
approximately the size of a full stop/period(.), in thecentre of the circle. The tattoo was used as a guidefor placing the template on the scalp surface atClin Drug Inve st 2009; 29 (5)HairMax LaserComb® Laser Phototherapy in Male Androgenetic Alopecia

subsequent VISitS for the hair clipping andmacroimages for hair density evaluation.
Macroimaging and Hair Oensity
Evaluation Procedures

Mocroimoge Acquisition

The subject sat in a chair and was correctly
placed in the stereotactic apparatus. The digital
image were standardized for lighting, camera angle
and position of the subject's head in each digital
image to achieve a similar camera angle and relative
image size. For macrodigital images a template as
described in the previous section was placed on thelenses for precise and consistent alignment on the
tattoo. A lOmm scale divided into 0.1 mm increments was etched into the template for calibration
purpo es during the hair density evaluations. The
images were recorded on compact flash cards.
During the subject's visit, the images werepreviewed to see if they were acceptable; unacceptable images were retaken. After the subject's visit
had been completed, the images were printed andsigned by the investigator and uploaded to a designated site for image archiving.
Image Analysis and Management

A state-of-the art software ystem was utilized
for image management. Macroimages were imported into a blinded subject file labelled by subject
number. The images displayed included a means ofmarking each individual hair. Each hair was 'clicked' and a running count was displayed at the bottomof the software window. Only terminal hairs werecounted. Archives of the counted hairs were maintained in the subject file. Images could be displayedside by side.
The database software functionality also allowed
subjects to be identified by number while the advanced multiple criteria searches facilitated quick
retrieval of information. In addition, the subject's
chart view allowed all of a subject's image to beviewed on one screen with scalable thumbnails.
Blinded subject record containing hair density
measurements were forwarded to data management
for inclusion in the study data ba e.
© 2009 Ad is Do l o Information BV. All rights reserved .

287

Study Endpoints

The primary efficacy endpoint was change in
non-vellus terminal hair density (hairs/cm 2) in thetarget region between baseline and endpoint (26weeks/6 months or the earlier termination visit), as
asses ed by scalp macroimaging using dot mappingand computer-aided hair counts (see Evaluation ofClinical Efficacy section). The techniques used werecomparable to those used in the protocol for minoxidil.
Secondary effectiveness endpoints were subjective global assessment of hair regrowth by subjects
and the investigator at week 26. Patients were asked
to complete the !!-question proprietary Subject
Questionnaire without assistance, aimed at evaluating perception of overall hair regrowth characteristics. These questions encompassed overall results,
rate of hair loss, assessment of dandruff, scalp
health, hair health, hair thickness, hair shine, hair
growth rate, manageability and hair colour changes.
Investigators were asked to evaluate the subject's
hair growth looking at the baseline and week 26/6
months (or early termination) visit global images(without reference to macroimages) and graded thehair growth on a 4-point scale.
The safety endpoints for the study were adverse
events of any nature and vital signs.
Statistical Analysis

Based on prior data for the HairMax
LaserComb®( 26l and the drug minoxidil (NDA20-834, Pharmacia and Upjohn Consumer Healthcare, November 14, 1999) the standard deviation ofchange from baseline in terminal hair density was
assumed to be 30 hairs/cm 2 . Based on this estimate,
93 subjects randomized 2: I (62 in the HairMax
LaserComb® group and 31 in the sham device
group) would provide 85% power to detect a difference of 20 hairs/cm 2 To allow for a 20% dropout
rate, 123 subject needed to be enrolled. Stati ticalcomparisons were made between treatment groups
for all baseline demographic variables. Continuous
variables were compared using two-sample t-tests:
dichotomous variables were compared u ing Pearson's chi- quared test (x 2 ) and ordinal variables by
Clin Drug Invest 2009: 29 (5)Leavitt et al.

288

the Cochran-Mantel-Haen zel procedure after a ignation of uniform cores (I, 2, 3, etc.) to the fourordered categorie of respon e.
The primary analy is of effectivene s wa performed on all randomized ubjects who had a po tba eline hair den ity measurement. The Ia t value
was carried forward for subjects who terminatedprematurely. All randomized ubject who u ed thetudy device at least once were included in analy es
of afety. The primary analy i of effectivenes wa
an analy i of covariance (A COY A), which included the effects of treatment group, tudy centre,age (a a continuou variable), and Fitzpatrick Skin
Type Scale cia ification (a a categorical variablewith four level ).
Adver e events were ummarized as the number
and percentage of subjects reporting each event.
Stati tical compari on were made between treatment group u ing Fi her' exact te t.
All tati tical analy e were two- ided at a 5%
level of ignificance.

Results
Study Population

A total of 123 ubject were enrolled at four
tudy ite . Table I hows the mean age, race andFitzpatrick Skin Type Scale cia sification of subTable I. Baseline demographics of the study population (males,n = 123)
Characteristic

Value

Age (y)Mean ± SD

47.9±8.7

Range

30-60

Race [n (%)]
White, non-Hispanic

111 (90.2)

Hispanic

9 (7.3)

Black

0 (0)

Other

3 (2.4)

Fitzpatrick Skin Type Scaleclassification [n (%)]
I

4 (3.3)II

17 (13.8)

Ill

65 (52.9)

IV

37 (30.1)

C 20CF/ Adis Data Information BV. All rights reseNed.

ject entered into the tudy . Seven ubject were
di continued from the study by the ponsor becau eof deviation from ba eline entry criteria. Thi wa
becau e the ite location cho en for the target areafor hair den ity evaluation wa found to be out ide
the zone of miniaturized hair . The tudy de ign
required tha t chosen sights for evaluation had tohave miniaturized hairs. One subject wa di continued becau e of noncompliance with tudy vi its.
One subject wa lo t to follow-up . Four ubjects
withdrew con ent for other reasons. Of the e fourubject , two ubject in the ham device group had
early termination vi it (at 71 and 11 2 day ) at
which hair den ity mea urement were completed.
Ten subject in the HairMax La erComb® group
who terminated prematurely were not included in
the primary analy i of effectivene , and one of thethree ubjects in the ham device group who terminated prematurely wa not included.
Primary Efficacy

As noted previously, hair count were performed
utilizing macroirnage imported into blinded patient
files by an evaluator who was not connected with theclinical trial. The two ubjects with the greate t
decrease in hair den ity ( ubject 04-039 in the ham
device group with -145 hairs/cm 2 and subject
01-039 with -56 hairs/cm 2) appeared to be outlier
in the stati tical analysi . The re idual standard
deviation wa u ed a an e tirnate of the accuracy ofthe dependent variable being mea ured, hair den ity.
The A COYA wa 18.6 hair /cm 2 and thee subjects had residuals of -128 .0 (subject 04-039) and-75.8 ( ubject 01-039). To a es the impact of
the e ubjects on analysis, they were removed andthe resu lt are shown in table II. Removal of the eubjects reduced the re idual standard deviationfrom 18.6 to 11 .2 hairs/cm 2 ; however, the impact of
the removal of the e two outlier subjects on the final
re ults wa negligible.
When the two outliers were excluded from theanaly i , ubjects treated with the H a irMax
La erComb® had a mean increa e in terminal hair
den ity of + 19. hair /cm 2 , while subjects in theham device group had a mean decrea e of -7.6
Clin Drug Invest 20CF/; 29 (5)289

HairMax LaserComb® Laser Phototherapy in Male Androgenetic Alopecia

Table II. Mean baseline and change from baseline to 26 weeks in terminal hair density" (hairs/cm 2 ) -two outliers excluded
Time

HairMax LaserComb®
(n = 71)

Sham device(n = 39)

Baselinemean ± SD

122.9 ± 51.4

120.7 ± 48.6

range

21 .6, 252.1

25.5, 225.4

Change from baselinemean ± SD

17.3 ± 11 .9- 8.9 ± 11 .7

range- 6.4 , 52.2

- 54 .7 , 7.6

Adjusted meanb

19.8

- 7.6

Difference (95% Cl)

27.4 (22.9 , 31 .9)

p-Value<0.0001a

Last value carried forward for subjects who terminated prematurely .

bAdjusted for study centre , subject's age and skin type .

hairs/cm 2 at the completion of the study (table II).
This difference wa significant (p < 0.000 l ). An
example of terminal hair regrowth in the non-vellus
hair density macroimages of one patient in the
HairMax LaserComb® group is hown in figure l.
Table III hows individual subject changes fromba eline in terminal hair density, divided into six
categorie . Only two subjects in the HairMax
La erComb® group (2.8%) had a decrease in hairdensity ~5 hair /cm2 , whereas 26 ubject in thesham device group (65 .0%) had a similar decrea e.
Furthermore, 62 subjects in the HairMax
La erComb® group (86 .1%) had an increa e in hairdensity >5 hairs/cm 2 , while only two subjects in theham device (5 .0%) group had such an increa e.

Significant improvements in overall hair regrowth
were demonstrated in terms of patients' subjective
a se sment (p < 0.0 I) at 26 weeks over ba eline.

Secondary Efficacy Analyses

Secondary effectiveness endpoints included subjects' asse ment of overall hair growth (table IV),
the investigator's global assessment of overall hair
growth (table IV), and re ponse to ten additionalquestions in the Subject Questionnaire. In each of
the following analyses, subjects who terminated prematurely had their last value carried forward to each
sub equent vi it.

Fig. 1. Non-vellus hair density macroimages at baseline and 6 months in one patient in the HairMax LaserComb<~> group (6-month image
shows evidence of ink spread) .

<C 2009 Adis Data Information BV. All rig hts reserved .

Clin Drug Invest 2009; 2Q (5)290Leav itt et al.

Table Il L Categorical changes from baseline to 26 weeks in terminal hair density•
Change in hair density/cm 2

HairMax LaserComb"' (n = 72)[n(%))

Sham device (n = 40)[n(%))S-20

1 (1.4)7 (17.5)~-20 to - 5

1 (1.4)19 (47 .5)~-5 too

3 (4 .2)

9 (22.5)>0 to 55 (6.9)3 (7.5)>5 to 2034 (47.2)2 (5.0)>2028 (38.9)

0 (0)

a

Last value carried forward for subjects who terminated prematurely.

As seen in table TV bowing subject ' asse smentof overall hair growth, the p-value for the comparison between treatment groups achieved stati ticalsignificance (p = O.Ol) at the last visit. Thus, subjects in the HairMax La erComb® group perceived
significantly greater improvement in hair regrowththan those in the sham device group at the end of thestudy.
The result of the investigator's global assessments of hair growth are also shown in table TV. No
substantial differences were seen between treatmentgroups within each assessment category (p = 0.45).
The discordant results between the investigator's
subjective global assessment shown in this table andthe objective hair density measurements shown intable II were assessed by comparing the medianchanges from baseline in terminal hair density within each treatment group and category of re ponse.
Medians are u ed rather than means to lessen theimpact of large decrea es. This assessment showedthat there was no correlation between medianchanges from baseline in actual terminal hair density
shown in table II and investigator subjective global
asse sment shown in table TV among subjects in the
HairMax LaserComb® group. These results question the validity of the investigator's subjective
global assessment because of their lack of any
agreement with actual terminal hair growth shownin table II. It also brings into question the validity of
global photography of hair due to the nwnerous
inherent variables that effect the appearance of hairat each evaluation point.
Of the ten additional questions remaining in the
end-of-study Subject Questionnaire after subjects'
assessment of overall hair regrowth (table TV), answers to seven were analysed statistically (threequestions- reduced dandruff, return to natural colour, and scalp irritation- were excluded because ofhigh proportions of 'not applicable' answers). For
the remaining seven question , the responses to five(slower hair loss, better calp health, thicker feeling
hair, more hine to hair and overall hair improve-

Table IV. Subjects' and investigator's assessment of overall hair regrow1h at week 26
Assessment

HairMax LaserComb"'[n(%)]

Sham device[n(%)]

Subjects' assessment at week 26

n = 76n = 39No grow1h

28 (36.8)

21 (53.9)

Minimal grow1h

30 (39.5)

16 (41 .0)

Moderate grow1h

17 (22.4)

2 (5 .1)

Dense grow1h

1 (1 .3)0 (0)Investigator' s assessment at week 26

n = 72n = 38No growth

46 (63.9)

22 (57.9)

Minimal grow1h

18 (25.0)

10 (26.3)

Moderate growth

7 (9 .7)

5 (13 .2)

Dense grow1h

1 (1.4)1 (2.6)ap-Value•

0.01

0.45

HairMax LaserComb"' vs sham device .

© 2009 Adis Data Informa tion BV. All rights reserved.

Clin Drug Invest 200Q; 2</ (5)HairMax LaserComb® Laser Phototherapy in Male Androgenetic Alopeciament) were statistically significantly different (p <0.05) between the groups, i.e. the assessments weresignificantly better ifl subjects in the HairMax
LaserComb® group compared with those in thesham device group. Although between-group differences in responses to the last two questions (fastergrowing hair, more manageable hair) did notachieve statistical significance (p < 0.05), a morefavourable overall assessment was observed for subjects in the HairMax LaserComb® group comparedwith those in the sham device group.
Safety and Tolerability

The HairMax LaserComb® device was found tobe well tolerated. No serious adverse effects werereported. The only adverse events considered to bepossibly device related were four cases of mild
paraesthesia and four cases of mild urticaria. These
showed no statistical difference between study
groups. Changes in vital signs from baseline werevery small in both treatment groups and similar
between both groups.
Discussion

While many unknowns remain , an importantcomponent of the treatment of AGA is to provide
non-biased demonstration of laser phototherapy effectiveness in hair growth stimulation in humans.
Here we report on the first known double-blind,
controlled trial of laser phototherapy for the treatment of AGA, that is, sex hormone-dependent malepattern hair loss. Overall, the results of the trial
demonstrate significantly greater increase in meanterminal hair density (primary effectiveness) in subjects treated with the HairMax LaserComb® device
over the sham device (p<O.OOOI). Consistent withthis evidence for primary effectiveness, significant
improvements in overall hair regrowth were demonstrated in terms of patients' subjective assessment(p < 0.0 I) at 26 weeks over baseline. Subjects in the
Hair Max LaserComb® group perceived significantly greater improvement (p < 0.05) regarding overall
hair improvement, slowing of hair loss, thicker feeling hair, better scalp health and hair shine.
@ 2009 Adis Data Info rmation BV. All rights reserved .

291

This study was a pivotol part of the Premarket
Notification 510(k) submission in February 2006
and subsequent clearance for marketing by the FDA
in January 2007. To date, no other laser therapy
device has been cleared by the FDA for marketing
and all other imilar products on the market are soldas cosmetic devices. This clearance means that the
HairMax LaserComb® has been the subject of arigorous review and clearance process, which differentiates it from other marketed devices that have noclinical proof of efficacy. Thus, it is impossible tocompare the HairMax LaserComb® with other devices marketed without clinical studies or FDA
clearance.
Conclusions

The current study has accomplished an importantgoal. This is the first study demonstrating efficacy inhair growth with a laser phototherapy device, theHairMax La erComb®. This randomized, doubleblind, sham device-controlled, multicentre efficacy
trial indicates that the HairMax LaserComb® laser
phototherapy device with its patented hair-parting
teeth mechanism is an effective, well tolerated treatment for hair loss of androgenetic aetiology. Indeed,the HairMax LaserComb® is currently the only laser
therapy device that has been clinically studied andproven to grow hair in males with certain cia es of
A GA.

In the future , the efficacy of HairMax
LaserComb® should also be evaluated in subjects
with hair loss of non-androgenetic aetiology. It will
also be very important to establish the cellular andmolecular mechanisms behind the hair growth-promoting effect oflaser phototherapy. Future researchshould help us to differentiate if laser phototherapy
predominantly: (i) stimulates anagen re-entry bytelogen hair follicles; (ii) increases rates of proliferation in active anagen hair follicles; (iii) prevents
premature catagen development; or (iv) extends theduration of the anagen phase. Cellular events, suchas activation of dormant hair follicle stem cells, orincrease in proliferation of hair matrix trichocytes,
should be investigated. In addition, subcellular andmolecular signalling events, such as direct shortClin Drug Invest 2009; ~ (5)Leavitt et al.

292

term activation of the mitochondrial electron-transport chain, or long-term up-regulation of growth
factors, should be evaluated.
Acknowledgements
This study was sponsored by Lexington International ,LLC. Mr D . Michaels is an employee of Lexington International, LLC. Dr M . Leavitt is a retained consultant andmedical advisor and Dr G . Charles is a non-retained medical
advisor to Lexington In ternational , LLC. Dr Eugene Heyman
has no conflicts of interest that are directly relevant to thecontent of this study. The authors would like to gratefully
acknowledge Dr Maksim Plikus for assistance with the compilation of this article.

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Correspondence: Dr Matt Leavitt, 2600 Lake Lucien Drive,
Ste 180, Matiland, FL 32751, USA.
E-mail: mlleavitt@aol.com

Clin Drug Invest 2009; 29 (5)