TRPV Expression in Subjects With Sensitive Skin

Sensitive Skin Clinical Trial

Official title:

Distribution and Expression of Non-neuronal Transient Receptor Potential (TRPV) Ion Channels in Sensitive Skin Syndrome.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT01871883
• Other study ID #: TRPV1SenSk
• Status: Enrolling by invitation
• Phase: Phase 4
• First received: May 27, 2013
• Last updated: November 30, 2015
• Start date: May 2013
• Est. completion date: September 2016

Study information

• Verified date: November 2015
• Source: Universidad Autonoma de San Luis Potosí
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 30
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Sensitive Skin

Intervention

Procedure:
• Skin biopsy
Two skin biopsies will be taken with a 3 mm punch in the retroauricular area. The procedure will be done by an investigator, under aseptic and antiseptic conditions and under local anesthesia with lidocaine and epinephrine. The incision will be sutured with 6-0 Nylon, and the stitches will be removed after 5 days. One biopsy will be processed for immunohistochemistry, the other for RNA extraction and analysis.
• Oral mucosa specimen
The sample for keratinocytes from oral mucosa will be taken with a Foam knife, which is a non-invasive procedure. It does not need anesthesia, and it does not leave scars. The procedure consists in gently brush the oral mucosa with the knife five times, and the material that will be obtained will be fixed in a PBS solution for RNA analysis.

Locations

Country	Name	City	State
Mexico	Dermatology Department. Hospital Central "Dr. Ignacio Morones Prieto"	San Luis Potosí

Sponsors (2)

Lead Sponsor	Collaborator
Universidad Autonoma de San Luis Potosí	Hospital Central "Dr. Ignacio Morones Prieto"

Country where clinical trial is conducted

Mexico, 

References & Publications (4)

Escalas-Taberner J, González-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. Review. Spanish. — View 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.

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. — View Citation

Ständer S, Schneider SW, Weishaupt C, Luger TA, Misery L. Putative neuronal mechanisms of sensitive skin. Exp Dermatol. 2009 May;18(5):417-23. Review. Erratum in: Exp Dermatol. 2009 Dec;18(12):1096. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	TRPV1 mRNA in biopsies	Quantify the expression of mRNA of TRPV1 in epidermal keratinocytes obtained by skin biopsies through RT-PCR	Up to 1 year	No
Other	TRPV1 in biopsies by immunohistochemistry	Quantify the expression of TRPV1 in epidermal keratinocytes obtained by skin biopsies through immunohistochemistry	Up to 1 year	No
Other	mRNA1 of TRPV1 in oral keratinocytes	Quantify the expression of mRNA of TRPV1 in epidermal keratinocytes obtained from oral mucosa through RT-PCR	Up to 1 year	No
Other	TRPV1 in oral keratinocytes by immunohistochemistry	Quantify the expression of TRPV1 in epidermal keratinocytes obtained from oral mucosa through immunohistochemistry.	Up to 1 year	No
Primary	Expression of TRPV1	Determine the expression of TRPV1 in patients with sensitive skin	Up to 1 year	No
Secondary	TRPV1 and Sensitive Skin	Correlate the expression of TRVP1 with the presence of sensitive skin syndrome	Up to 1 year	No
Secondary	TRPV1 and skin phototype	Identify variations in the expression of TRPV1 according to skin phototype	Up to 1 year	No
Secondary	TRPV1 and barrier function	Correlate the expression of TRPV1 with the transepidermal water loss as an indirect measure of barrier function.	Up to 1 year	No