Effects of Hypericum Perforatum Oil on Promoting Skin Recovery in Different Human Skin Damage Models

• ClinicalTrials.gov Identifier: NCT03783819
• Recruitment Status: Completed
• First Posted: December 21, 2018
• Last Update Posted: February 21, 2020
• Sponsor: University of Split, School of Medicine
• Information provided by (Responsible Party): University of Split, School of Medicine

Study Description

Brief Summary:

Saint John's wort (Hypericum perforatum) was recognised as a traditional, folk medicine used topically for the treatment of wounds, abrasions, burns, sunburns and inflammatory skin disorders.

Its use in wound healing could be justified with its anti-inflammatory, antimicrobial and astringent effects. It also stimulated tissue growth and cell differentiation, as one of Hypericum perforatum's main ingredients, hyperforin, was shown to activate TRPC6 channel which had been recognised as an activator of keratinocyte differentiation. Another potentially useful activities could be its inhibitory effects on epidermal Langerhans cells.

Furthermore, in vivo research showed its potential with improved wound healing in different rat models. Finally, several clinical studies were performed testing its effects in atopic dermatitis treatment, wound healing after caesarean section and episiotomy, as well as healing of post-surgical scalp wounds, bed sores and venous ulcers.

The aim of the study will be to determine the effectiveness of ointment containing Hypericum perforatum oil on promoting skin recovery in different human skin damage models on healthy volunteers, in comparison to placebo.

Chosen test sites will be the forearms. One forearm will be treated will the formulation containing Hypericum perforatum oil while the other will be treated with the placebo formulation. Four test sites will be marked on each forearm with skin barrier damage induced on three areas while the fourth will be left intact. Treated forearm and test sites sequence on forearms will be prospectively randomized (double randomization).

First skin damage model used in the trial will be sodium lauryl sulphate (SLS) induced irritation. The SLS solution will be placed on the skin of participants under the occlusion for 24 hours. Second model will be the tape-stripping procedure with defined TEWL value set as an endpoint. The final model will be damage by the UV radiation. UV irradiation will be performed under strict conditions with use of the necessary safety equipment. Only the defined test areas will be irradiated with the defined dose of radiation.

Condition or disease	Intervention/treatment	Phase
Skin Recovery in Different Human Skin Damage Models	Other: Hypericum perforatum oil; Other: Placebo; Procedure: SLS induced irritation; Procedure: Tape-stripping; Procedure: UV radiation; Procedure: Intact skin	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Hypericum Perforatum Oil on Promoting Skin Recovery in Different Human Skin Damage Models, Randomized Controlled Trial
• Actual Study Start Date: February 4, 2019
• Actual Primary Completion Date: March 29, 2019
• Actual Study Completion Date: March 29, 2019

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Active treatment; One forearm will be treated with ointment containing Hypericum perforatum oil. Forearm (left or right) will be chosen according to randomization protocol.	Other: Hypericum perforatum oil; Ointment containing Hypericum perforatum oil; Procedure: SLS induced irritation; 60 uL of 1% w/v sodium lauryl sulphate (SLS) will be applied to skin under occlusion by large Finn chamber for 24 hours as described in the guidelines by Standardization group of European Society of Contact Dermatitis. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: Tape-stripping; Skin barrier disruption will be induced by tape-stripping. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: UV radiation; UV radiation will be used to induce skin erythema and damage. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: Intact skin; Healthy, intact skin. Procedure will be performed to specified skin sites, according to randomization protocol.
Placebo Comparator: Placebo treatment; Other forearm will be treated with placebo ointment. Forearm (left or right) will be chosen according to randomization protocol.	Other: Placebo; Ointment containing plant oils used in Hypericum perforatum oil production and dye; Procedure: SLS induced irritation; 60 uL of 1% w/v sodium lauryl sulphate (SLS) will be applied to skin under occlusion by large Finn chamber for 24 hours as described in the guidelines by Standardization group of European Society of Contact Dermatitis. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: Tape-stripping; Skin barrier disruption will be induced by tape-stripping. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: UV radiation; UV radiation will be used to induce skin erythema and damage. Procedure will be performed to specified skin sites, according to randomization protocol.; Procedure: Intact skin; Healthy, intact skin. Procedure will be performed to specified skin sites, according to randomization protocol.

Outcome Measures

Primary Outcome Measures :

1. Transepidermal water loss change [ Time Frame: Assessments will be performed on 1st, 2nd, 3rd, 4th, 5th, 8th and 11th day of the trial (baseline measurements and change from baseline assessment). ]
   Tewameter will be used to assess skin barrier function as a measurement of the water loss (g/hm2).
2. Stratum corneum hydration change [ Time Frame: Assessments will be performed on 1st, 2nd, 3rd, 4th, 5th, 8th and 11th day of the trial (baseline measurements and change from baseline assessment). ]
   Corneometer will be used to estimate skin dryness. It is a relative measurement and uses arbitrary units (AU).
3. Erythema change [ Time Frame: Assessments will be performed on 1st, 2nd, 3rd, 4th, 5th, 8th and 11th day of the trial (baseline measurements and change from baseline assessment). ]
   Mexameter will be used to assess erythema. It is a relative measurement and uses arbitrary units (AU).
4. Melanin content change [ Time Frame: Assessments will be performed on 1st, 2nd, 3rd, 4th, 5th, 8th and 11th day of the trial (baseline measurements and change from baseline assessment). ]
   Mexameter will be used to assess skin melanin content. It is a relative measurement and uses arbitrary units (AU).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

- young, healthy volunteers who gave written informed consent

Exclusion Criteria:

• skin disease, skin damage on measurement sites
• use of corticosteroids, antihistamines and immunomodulators a month prior the inclusion and during the trial
• use of drugs that may cause photosensitivity
• use of emollients three days prior the inclusion in the trial
• non-adherence to the trial protocol
• exposure to artificial and excessive natural UV radiation
• pregnancy and lactation
• skin cancer
• history of vitiligo, melasma and other pigmentation and photosensitivity disorders
• immunosuppression
• allergic or irritant reactions to the constituents of the two ointments (active and placebo) and similar chemicals (e.g. salicylic and benzoic acid)

Contacts and Locations

Locations

Croatia

School of Medicine

Split, Croatia, 21000

Sponsors and Collaborators

University of Split, School of Medicine

Investigators

• Principal Investigator: Dario Leskur, MPharm; University of Split, School of Medicine

More Information

Publications:

Wolfle U, Seelinger G, Schempp CM. Topical application of St. John's wort (Hypericum perforatum). Planta Med. 2014 Feb;80(2-3):109-20. doi: 10.1055/s-0033-1351019. Epub 2013 Nov 8.

Jaric S, Kostic O, Mataruga Z, Pavlovic D, Pavlovic M, Mitrovic M, Pavlovic P. Traditional wound-healing plants used in the Balkan region (Southeast Europe). J Ethnopharmacol. 2018 Jan 30;211:311-328. doi: 10.1016/j.jep.2017.09.018. Epub 2017 Sep 21.

Schempp CM, Winghofer B, Ludtke R, Simon-Haarhaus B, Schopf E, Simon JC. Topical application of St John's wort (Hypericum perforatum L.) and of its metabolite hyperforin inhibits the allostimulatory capacity of epidermal cells. Br J Dermatol. 2000 May;142(5):979-84. doi: 10.1046/j.1365-2133.2000.03482.x.

Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD. A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Dev Cell. 2012 Oct 16;23(4):705-15. doi: 10.1016/j.devcel.2012.08.017. Epub 2012 Sep 27.

Suntar IP, Akkol EK, Yilmazer D, Baykal T, Kirmizibekmez H, Alper M, Yesilada E. Investigations on the in vivo wound healing potential of Hypericum perforatum L. J Ethnopharmacol. 2010 Feb 3;127(2):468-77. doi: 10.1016/j.jep.2009.10.011. Epub 2009 Oct 13.

Thandar Y, Gray A, Botha J, Mosam A. Topical herbal medicines for atopic eczema: a systematic review of randomized controlled trials. Br J Dermatol. 2017 Feb;176(2):330-343. doi: 10.1111/bjd.14840. Epub 2016 Nov 30.

Schempp CM, Windeck T, Hezel S, Simon JC. Topical treatment of atopic dermatitis with St. John's wort cream--a randomized, placebo controlled, double blind half-side comparison. Phytomedicine. 2003;10 Suppl 4:31-7. doi: 10.1078/1433-187x-00306.

Lavagna SM, Secci D, Chimenti P, Bonsignore L, Ottaviani A, Bizzarri B. Efficacy of Hypericum and Calendula oils in the epithelial reconstruction of surgical wounds in childbirth with caesarean section. Farmaco. 2001 May-Jul;56(5-7):451-3. doi: 10.1016/s0014-827x(01)01060-6.

Samadi S, Khadivzadeh T, Emami A, Moosavi NS, Tafaghodi M, Behnam HR. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Altern Complement Med. 2010 Jan;16(1):113-7. doi: 10.1089/acm.2009.0317.

Hajhashemi M, Ghanbari Z, Movahedi M, Rafieian M, Keivani A, Haghollahi F. The effect of Achillea millefolium and Hypericum perforatum ointments on episiotomy wound healing in primiparous women. J Matern Fetal Neonatal Med. 2018 Jan;31(1):63-69. doi: 10.1080/14767058.2016.1275549. Epub 2017 Feb 23.

Lauchli S, Hafner J, Wehrmann C, French LE, Hunziker T. Post-surgical scalp wounds with exposed bone treated with a plant-derived wound therapeutic. J Wound Care. 2012 May;21(5):228, 230, 232-3. doi: 10.12968/jowc.2012.21.5.228.

Tupker RA, Willis C, Berardesca E, Lee CH, Fartasch M, Agner T, Serup J. Guidelines on sodium lauryl sulfate (SLS) exposure tests. A report from the Standardization Group of the European Society of Contact Dermatitis. Contact Dermatitis. 1997 Aug;37(2):53-69. doi: 10.1111/j.1600-0536.1997.tb00041.x.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leskur D, Perisic I, Romac K, Susak H, Seselja Perisin A, Bukic J, Rusic D, Kladar N, Bozin B, Modun D. Comparison of mechanical, chemical and physical human models of in vivo skin damage: Randomized controlled trial. Skin Res Technol. 2021 Mar;27(2):208-216. doi: 10.1111/srt.12932. Epub 2020 Jul 20.

• Responsible Party: University of Split, School of Medicine
• ClinicalTrials.gov Identifier: NCT03783819
• Other Study ID Numbers: 2181-198-03-01-18-0058
• First Posted: December 21, 2018
• Last Update Posted: February 21, 2020
• Last Verified: February 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Split, School of Medicine:

Hypericum perforatum; Saint John's Wort; St. John's Wort