hydeal-d

Acido ialuronico e salute della donna:
Nuove prospettive di ricerca clinica
Paolo Sala
UO Ostetricia e Ginecologia
IRCCS AOU San Martino IST - Istituto Nazionale per la Ricerca sul Cancro
Nuove prospettive di ricerca clinica
Ginecologia e Uroginecologia
Ortopedia
Dermatologia
Medicina Estetica
Odontoiatria
Oftalmologia
Neurologia
Acido ialuronico
Molecola dalle molteplici proprietà e
applicazioni cliniche
Gynecological Service, Department of Surgery
Memorial Sloan Kettering Cancer Center
New York, USA
Protocol Information:
Activation Date: Nov. 2012
Date 1st Enrollment: June 2013
Date Last Enrollment: April 2015
Accrual:
Target: 60
#Enrolled-to-Date: 35
#Eligible: 35
#Evaluable (for at least 1 study objective): 35
# Actively Undergoing Protocol Treatment: 4
# Off-Study: 31
Gynecological Service, Department of Surgery
Memorial Sloan Kettering Cancer Center
New York, USA
Eligible participants included those with a
history of breast cancer receiving treatment
with an aromatase inhibitor (AI) at the time
of enrollment
INTERVENTION
to use HLA daily for 2 weeks, then 3 times per week for 12‐14 weeks
STUDY OUTCOMES
Vaginal Assessment Scale (VAS)
Patient‐reported outcomes (PROs) of the Sexual Activity Questionnaire (SAQ)
Sexual Self‐Schema Scale
Female Sexual Function Index (FSFI)
PROMIS sexual function items
RESULTS
29 patients enrolled at baseline and 22 at 4‐6 weeks
55% (n=16/29) reported sexual activity at baseline, which increased to 64% (n=14/22) at 4‐6
weeks
On the VAS, 59% (n=17/29) reported symptoms of severe dryness at baseline and 48%
(14/29) reported severe dyspareunia; these symptoms decreased to 5% (n=1/22) and 5%
(n=1/22), respectively, at 4‐6 weeks
Vaginal pH scores were greater than 6.5 in 24% (n=7/29) at baseline; by 4‐6 weeks, only 18%
(n=4/22) had a pH in this elevated range
83% (n=24/29) had pain with pelvic exams at baseline (24%, n=7/29 severe) and 73%
(n=16/22) had pain at 4‐6 weeks (none severe)
HLA vaginal gel may improve vaginal/sexual health issues and concerns of
breast cancer survivors both in their perceived symptoms
and on clinical exam
University of Texas
MD Anderson Cancer Center
(UTMDACC)
• Prospective, Randomized clinical study
Study Center: University of Texas MD Anderson Cancer Center
• 168 women in adjuvant therapy with AIs
• Investigate if intervention with combined behavioral sex therapy
and non hormonal vaginal moisturizers (HYALOgyn®/Luvena)
can reduce both dyspareunia rates and early discontinuation of
AIs
• Primary endpoint: to reduce rates of sexual dysfunction associated with
adjuvant therapy with Ais
• Secondary endpoints:
 to test whether preventing sexual dysfunction can decrease rates of early
discontinuation of AIs
 to compare efficacy of two new types of non-hormonal vaginal moisturizer
(HyaloGyn Luvena) in preventing dyspareunia
•58 women completed baseline (4 have dropped out of the
study)
•34 completed both baseline and 6-month follow-up
questionnaires.
Preliminary results:
•The 3 groups have disparate scores at baseline on the
Menopausal Sexual Interest Questionnaire (total score is a
combination of desire, responsiveness, and satisfaction)
Even in a small group of women, HYALOgyn continues to produce
the largest, positive change.
Repeated-measures ANOVA, just between-group analyses at
baseline and 6-months:
Between groups one-way ANOVA, baseline: P<0.069
Between groups one-way ANOVA, 6-month: P<0.042
GROUP
N
BASELINE MSIQ MEAN
(SD)
6-MO FOLLOW-UP MSIQ
MEAN (SD)
Mean within-group
change
USUAL CARE
12
34.09 (13.05)
LUVENA
11
23.73 (12.14)
HYALO-GYN
11
37.00 (15.36)
31.91 (13.52)
27.55 (16.16)
43.00 (12.41)
-2.18
3.82
6.00
Benchmark survey mean for women on AIs 18-24 months: 22.6 (11.6)
Tendrils web intervention study: Group exposed to web site + 3 counselling
sessions: Baseline 18.0 to post-treatment 31.22
Randomized multicenter spontaneous prospective clinical
trial to assess the efficacy and safety of Hydeal-D versus
usual care on promoting the restoration of sexual function
in the postpartum period
Primary outcome measures
FSFI questionnaire score
Secondary outcome measures
− Evaluation of sexual function through three items of
FSFI questionnaire (lubrication-pain-arousal)
− Vaginal pH (using a pH indicator dipstick)
− Interval time between the delivery and the restart of
sexual intercourses (in weeks)
− Edinburgh Postnatal Depression Scale (EPDS)
− PC Test for the pubococcygeus muscle contractility
− Vaginal perineal pain determined using a VAS scale
− Coinvestigator global assessment (COG)
(tolerability, vaginal dryness, satisfaction, perineal
pain)
Randomized multicenter spontaneous prospective clinical
trial to assess the efficacy and safety of Hydeal-D versus
usual care on promoting the restoration of sexual function
in the postpartum period
STUDIO CLINICO DI FASE IV POSTMARKETING
DESCRIZIONE DELL’INTERVENTO
− Gruppo di studio
1 applicazione vaginale di Hydeal-D ogni 3 giorni per
12 settimane consecutive dal 40° giorno postparto
− Gruppo di controllo
usual care (detergente neutro)
Randomized multicenter spontaneous prospective clinical
trial to assess the efficacy and safety of Hydeal-D versus
usual care on promoting the restoration of sexual function
in the postpartum period
Backgroung information and scientific rationale
Hames CT. Sexual needs and interests of postpartum couples. JOGN Nurs. 1980 Sep-Oct;9(5):313-5
von Sydow K. Sexuality during pregnancy and after childbirth: a metacontent analysis of 59 studies. J Psychosom Res. 1999
Jul;47(1):27-49
Bitzer J, Alder J. Sexuality during pregnancy and the postpartum period. J Sex Educ Ther 2000; 25: 49-58
Randomized multicenter spontaneous prospective clinical
trial to assess the efficacy and safety of Hydeal-D versus
usual care on promoting the restoration of sexual function
in the postpartum period
Razionale dello studio
Efficacy
Safety
Hydeal-D
Vaginal
tissue
repair
Sexual
function
restoration
Randomized multicenter spontaneous prospective clinical
trial to assess the efficacy and safety of Hydeal-D versus
usual care on promoting the restoration of sexual function
in the postpartum period
Razionale dello studio
Chemiotassi
cellule per la
riparazione
tissutale
Ristabilimento
della funzione
sessuale
Trattamento
dell’atrofia
vaginale
Tempera, G. Evaluation of the tolerability and efficacy of Hyalgel Vaginal Gel for the
treatment of vaginal dryness and irritation, 1998
Grimaldi EF et al. Role of high molecular weight hyaluronic acid in postmenopausal vaginal discomfort. Minerva Ginecol. 2012 Aug;64(4):321-9
Il concetto di Peso Molecolare (HA)
CH2OH
OH
OH
O
O
OH
O
NHCOCH3
O
O
O
HA monomero
n = 4 apoptosi
…
…
n = 12 neo-angiogenesi
n = 150-800 antimicrobico/
modulatore infiammazione
…
n = <1500 assemblaggio ECM
…
n = >2000 idratazione/viscoelastico
Acido ialuronico e turgore cutaneo
potente idratante naturale
L’ acido ialuronico (HA) è conosciuto come “idratante
naturale” poichè UNA molecola di HA può legare fino
a 109 molecole di H2O
1 g di HA può legare fino a
3 litri di H2O
1 molecola di HA può legare fino
109 molecole di H2O
Acido ialuronico
ruolo fisiologico cutaneo
L’ acido ialuronico presente nella matrice extracellulare consente un ″alto
grado di idratazione″
TURGORE CUTANEO
Mediante il legame con specifici recettori cellulari l’ HA influenza la
proliferazione e la motilità delle cellule, l’ angiogenesi ecc.
TROFISMO CUTANEO
L’ acido ialuronico è un potente scavenger dei radicali liberi
PROTEZIONE DELLA BARRIERA CUTANEA
Acido ialuronico
ruolo biologico
LEGAME A RECETTORI SPECIFICI
cheratinociti
CD44
Il legame recettoriale
consente
AZIONI BIOLOGICHE
SPECIFICHE
RHAMM
fibroblasti
ICAM-1
cellule endoteliali
Proliferation
Angiogenesis
Macrophage
Endothelial cell
RUOLO ATTIVO
Product
Manufacturer or
Ingredients
Indications/Claims
Posology
Condom
Compatibility a
Distributor
Hyalo Gyn® gel
Fidia Farmaceutici,
Water, Hydeal-D® (hyaluronic acid derivative),
propylene glycol, carbomer 974P, methylparaben,
propylparaben, sodium hydroxide
Hydration and lubrication to
enhance the ease and comfort
of intimate sexual activity
Recommended:
1application
every 3 days for
30 days
Yes (lubricated/
non-lubricated latex,
lubricated polyurethane,
and l bricated natural skin
condoms)
Replens® gel
Sandoz - Novartis
Water, polycarbophil, mineral oil, glycerin,
hydrogenated palm oil glyceride, carbomer
homoploymer type B, sorbic acid, sodium hydroxide
Long-lasting vaginal
moisturizer, for routine use and
as a sexual lubricant
Recommended:
1application
every 3 days,
Yes
Vidermina® gel
Istituto Ganassini
Water, glycerin, propylene glycol, sorbitol, carbomer,
sodium hyaluronate, hydrolyzed glycosaminoglycans,
panthenol, Chamomilla recutita extract, arginine, PEG40 hydrogenated castor oil, imidazolidinyl urea,
methylparaben, propylparaben, disodium EDTA
Genital lubricant (external
use recommended)
1application/day
for 6 days
Yes
Finderm forte®
ovuli
Finderm
lalophil 10 mg (sodio ialuronico e policarbophil);
acido 18beta glicirretico 25 mg; vitamina A 6000 UI (da
vitamina A polmitato 10 UI/g); olio disemi di soia;
glicerilmonosterarato; involucro: gelatina; glicerina;
titaniobiossido.
Indicato nei casi di ectopia e
comunque, come coadiuvante
nei processi riparativi negli
stati atrofici e distrofici della
mucosa vaginale
1 ovulo/die
Filme Gyno®
ovuli
Hulka
Tocoferolo acetato 500 mg. Involucro: gelatina,
glicerolo
Ripristino dell’idratazione della
superficie vaginale in donne
con sensazione di fastidio,
bruciore, prurito, arrossamento,
irritazione, disagio nei rapporti
sessuali, non patologica.
Favorisce i fisiologici processi
trofici e riparativi della mucosa
vaginale.
1 ovulo/die
Hyalo Gyn gel vaginale

Gel vaginale a base di HYDEAL-D

Medical Device (510K, CE 0459)

1 Applicazione ogni 3 giorni (elevata compliance)

Capace di reidratare la mucosa incrementando la naturale attività
riparativa dell’epitelio

Coadiuvante del naturale processo di guarigione delle microlesioni da
attrito della mucosa vaginale

Biocompatibile con il microambiente vaginale

Incolore, non unge, non profumato
HYDEAL-D® technology
RILASCIO GRADUALE DI HY NATIVO
HY-COOH
R = alcool benzilico
+
R-OH
HY-COOR + H2O
HYDEAL-D® MECCANISMO DI DEGRADAZIONE
In contatto con le esterasi cutanee, HYDEAL-D è degradato in HY nativo
1)Idrolisi del legame estere
2) Rilascio di HY e alcool
benzilico
3) L’ HY e l’ alcool vengono
eliminati attraverso vie
metaboliche note
OH
+
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
Campoccia et al. Biomaterials. Vol 19, 2101-2127; 1998
HYDEAL-D®
PROPRIETA’ MUCO-ADESIVE
HYDEAL-D sembra rimanere maggiormente adeso alla superficie della mucosa per più tempo.
Dopo l'ultimo ciclo di lavaggio (soluzione fisiologica) la quantità di campione HYDEAL-D ancora
aderente alla mucosa è circa 30% maggiore rispetto a acido ialuronico non modificato.
HYDEAL-D ® è in grado di aderire alle superficie della mucosa, rilasciando
gradualmente il suo contenuto di acqua e quindi agisce come un agente
idratante.
Prospective multicenter randomized placebo controlled
clinical study to assess the effectiveness and the safety of
a hyaluronic based product, HYALOGYN ovules on
the treatment of vaginal atrophy in postmenopause
Primary Endpoint
To evaluate the efficacy of HYALOGYN ovules versus Placebo in the
treatment of vaginal symptoms associated with vulvovaginal atrophy
−Atrophy Symptoms Questionnaire (ASQ)
−Vaginal Health Assessment (VHA)
Prospective multicenter randomized placebo controlled
clinical study to assess the effectiveness and the safety of
a hyaluronic based product, HYALOGYN ovules on
the treatment of vaginal atrophy in postmenopause
Secondary Endpoint
− Evaluation of symptoms associated with atrophy (itching, burning and dyspareunia)
through VAS
− Vaginal pH (using a pH indicator dipstick)
− Evaluation of the presence of perineal pain through VAS
− Assessment of sexual function through questionnaires
Female Sexual Function Index (FSFI)
Female Sexual Distress Scale-Revised (FSDS-R)
− Subjective evaluation by the examiner regarding vulvovaginal atrophy through VAS
− PC Test for the pubococcygeus muscle contractility
− Evaluation of the patient’s perception on global improvement and efficacy index
Clinical Global Impressions (CGI)
− Adverse events (AEs) recording
Perspectives
Azione sinergica con gli ESTROGENI LOCALI
Azione sinergica con il LASER
Applicazioni sulla paziente radiotrattata
Trattamento dell’incontinenza urinaria femminile
Grazie per l’attenzione