Clinical trial NCT01871883: TRPV Expression in Subjects With Sensitive Skin
Official title: Distribution and Expression of Non-neuronal Transient Receptor Potential (TRPV) Ion Channels in Sensitive Skin Syndrome.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Sensitive Skin
Keywords: Sensitive skin
Transient potential receptor vanilloid 1
TRPV1
Transepidermal water loss
Skin Phototype
Lactic acid test
Skin irritancy tests
Lead sponsor: Universidad Autonoma de San Luis Potosí
Sponsor class: OTHER
Collaborators: name: Hospital Central "Dr. Ignacio Morones Prieto"
First posted: 2013-06-07
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: Sensitive skin syndrome is defined as the presence of burning, itching or any other unpleasant sensation on the skin, due to physical, chemical or psychological factors. It is frequently a self-diagnosed condition, and there are no accurate tests to recognize or quantify it because of the individual variations in perception and intensity of the related symptoms. The most accepted physiopathogenic theory is the presence of an altered barrier function of epidermis. Also, changes in the pH of the stratum corneum have been found to induce skin sensitivity through the activation of the transient potential receptor vanilloid (TRPV) neuronal receptors.

TRPV1 has been found in human keratinocytes, although its physiologic role in the skin is not yet established. Their presence in keratinocytes and cutaneous nervous fibers suggests a role in the sensitive function of the epidermis. Since this receptors can be activated by low pH (\< 5.9), which is also important for the development of sensitive skin, we hypothesized that an increase in the expression of these receptors can be the responsible for the syndrome.

Detailed description: Sensitive skin syndrome is defined as the presence of burning, itching or any other unpleasant sensation on the skin, due to physical, chemical or psychological factors. It is frequently a self-diagnosed condition, and there are no accurate tests to recognize or quantify it because of the individual variations in perception and intensity of the related symptoms.

Although the pathogenesis of sensitive skin syndrome is not completely understood, the most accepted theory is the presence of an altered barrier function. Irritation results from the abnormal penetration of substances to deeper layers of the skin, where they can induce vasodilation and stimulate c-type neuronal fibers. Also, changes in the pH of the stratum corneum have been found to induce skin sensitivity through the activation of the transient potential receptor vanilloid (TRPV) neuronal receptors.

TRPV1 was first discovered in 1997, when it was identified as the specific receptor for capsaicin in a subgroup of nociceptors. It is a non-selective thermo-sensitive cationic channel that can be found in nerves from the central and peripheral nervous system, fibroblasts, smooth muscle, mast cells, endothelial cells, gastrointestinal, respiratory and urinary epithelial cells. TRPV1 can be activated by excessive heat (\>42ºC), acidic pH (\< 5.9), and also by endogenous substances such as N- arachidonoyl dopamine, leucotriene B, phospholipase C, and many others.

In 2001, the functional expression of TRPV1 was identified in human keratinocytes. Their physiologic role in the skin has not been completely understood, but they have been related to differentiation, proliferation, inflammation and homeostasis of the epidermal barrier. Their presence in keratinocytes and cutaneous nervous fibers suggests a role in the sensitive function of the epidermis. It has been proved that the stimulation of TRPV1 in neuronal cells can induce pruritus and burning sensation. In vitro studies have demonstrated that the exogenous stimulation of TRPV1 in keratinocytes induces the release of nitric oxide, ATP, dopamine, prostaglandins, and other pro-inflammatory substances that can act as paracrine mediators between keratinocytes and cutaneous nerve fibers. Therefore, there are scientific bases to hypothesize that an increase in the expression of these receptors can be the responsible for the sensitive skin syndrome.

Eligibility criteria: Inclusion Criteria:

* Age \> 18 years old
* Known response to the lactic acid stinging test
* Informed signed consent

Exclusion Criteria:

* Any dermatoses in the test area
* Use of topical medications in the test area
* Personal history of keloid or hypertrophic scarring
* Known allergy to lidocaine
* Know heart disease
* Pregnancy
* Breastfeeding

Primary outcomes:
measure: Expression of TRPV1
timeFrame: Up to 1 year
Secondary outcomes:
measure: TRPV1 and Sensitive Skin
timeFrame: Up to 1 year
measure: TRPV1 and skin phototype
timeFrame: Up to 1 year
measure: TRPV1 and barrier function
timeFrame: Up to 1 year
Other outcomes:
measure: TRPV1 mRNA in biopsies
timeFrame: Up to 1 year
measure: TRPV1 in biopsies by immunohistochemistry
timeFrame: Up to 1 year
measure: mRNA1 of TRPV1 in oral keratinocytes
timeFrame: Up to 1 year
measure: TRPV1 in oral keratinocytes by immunohistochemistry
timeFrame: Up to 1 year
Locations:
city: San Luis Potosí
country: Mexico
facility: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
Study officials:
affiliation: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
name: Adriana Ehnis-Pérez, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
name: Juan P Castanedo-Cázares, MD
role: STUDY_DIRECTOR
affiliation: Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"
name: Bertha Torres-Álvarez, MD
role: STUDY_CHAIR
References:
citation: Hernández-Blanco D, Castanedo-Cázares JP, Ehnis-Pérez A, Jasso-Ávila I, Conde-Salazar L, Torres-Álvarez B. Prevalence of sensitive skin and its biophysical response in a Mexican population. World J Dermatol 2013;2:1-7. doi:10.5314/wjd.v2.i1.1.
citation: Escalas-Taberner J, Gonzalez-Guerra E, Guerra-Tapia A. [Sensitive skin: a complex syndrome]. Actas Dermosifiliogr. 2011 Oct;102(8):563-71. doi: 10.1016/j.ad.2011.04.011. Epub 2011 Jul 14. Spanish.
citation: Kueper T, Krohn M, Haustedt LO, Hatt H, Schmaus G, Vielhaber G. Inhibition of TRPV1 for the treatment of sensitive skin. Exp Dermatol. 2010 Nov;19(11):980-6. doi: 10.1111/j.1600-0625.2010.01122.x.
citation: Stander S, Schneider SW, Weishaupt C, Luger TA, Misery L. Putative neuronal mechanisms of sensitive skin. Exp Dermatol. 2009 May;18(5):417-23. doi: 10.1111/j.1600-0625.2009.00861.x.