Itch Relieving Effect of Botox: a Study in Healthy Subjects

Pruritus Clinical Trial

Official title:

Itch Relieving Effect of Botox: a Study in Healthy Subjects

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02639052
• Other study ID #: 23230
• Secondary ID: 126938
• Status: Active, not recruiting
• Phase: Phase 1
• First received: December 18, 2015
• Last updated: August 29, 2016
• Start date: February 2016
• Est. completion date: January 2017

Study information

• Verified date: July 2016
• Source: Temple University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if Botox is effective in the treatment of an experimentally induced itch that mimics chronic itch in healthy volunteers.

Description:

Several studies have shown that botulinum toxin type A (BoNT/A) has an antipruritic effect due to the inhibition of acetylcholine and other pruritic factors, such as substance P and glutamate. For instance, subcutaneous BoNT/A improves itch accompanied to hand eczema, dermatitis, lichen simplex, and rhinitis. Furthermore, a double-blind, placebo-controlled study showed that BoNT/A reduced histamine itch intensity in healthy men. Since acetylcholine has been shown to mediate itch in atopic dermatitis, this study aims to test the itch relieving effect of BoNT/A on a non-histaminergic model for chronic itch. This non-histaminergic model using the plant cowhage induces itch by activating protease activated receptor 2 (PAR2) receptors, which play a role in the itch of atopic dermatitis, also making this model better suited to test the efficacy of BoNT/A to relive chronic itch.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 35
• Est. completion date: January 2017
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

Inclusion Criteria:

1. Healthy volunteers between 18 and 50 years of age.

2. Must be in general good health with no disease or physical conditions that would impair evaluation of itch and pain perception.

3. No history of chronic itch or pain.

4. Must abstain from the use of any systemic or topical anti-histamine, steroid, or pain relief medications from the week prior to the study till the completion of the study.

5. Must abstain from the use of moisturizers on the arm.

Exclusion Criteria:

1. Individuals under 18 or over 50 years of age.

2. Inability to complete the required measures.

3. The presence of an itchy skin disease.

4. Diagnosis of diseased that would affect itch or pain perception (e.g. neuropathies).

5. Currently enrolled in any investigational study in which the subject is receiving any type of drug, biological, or non-drug therapy.

6. Use of oral, topical analgesics, or other medications known to interfere with itch or pain perception in the week prior to the study and throughout the study (e.g. antihistamines, anesthetics, opioids, neuroleptics, etc.).

7. Use of emollients on the arms a week prior to the study and throughout the study.

8. Use of anti-depressants, anti-psychotics, and illicit drugs.

9. Known history of neuropathy, uremia, uncontrolled thyroid disease, and diabetes mellitus.

10. Use of Botulinum toxin in the last year.

11. Known allergies to Botox.

12. Pregnant women. (Women of child bearing potential will undergo an human chorionic gonadotrophin (hCG) pregnancy test before Botox application).

13. Hypersensitivity to any botulinum toxin preparation or to any of the components in the formulation.

14. Infection at the injection site.

15. Cardiovascular disease.

16. Neuromuscular disorder (e.g., amyotrophic lateral sclerosis, myasthenia gravis, or Lambert-Eaton syndrome).

17. Compromised respiratory function.

18. Dysphagia.

19. History of urinary tract infection.

20. History of urinary retention.

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Pruritus

Intervention

Drug:
• Botox
10 units of Botox will be intradermally injected into one 4x4cm area on the volar forearm on 1st study visit.
• Saline
10 units of the Saline vehicle will be intradermally injected into one 4x4cm area on the contralateral volar forearm on the 1st study visit.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Temple University	Allergan

References & Publications (13)

Cui M, Khanijou S, Rubino J, Aoki KR. Subcutaneous administration of botulinum toxin A reduces formalin-induced pain. Pain. 2004 Jan;107(1-2):125-33. — View Citation

Gazerani P, Pedersen NS, Drewes AM, Arendt-Nielsen L. Botulinum toxin type A reduces histamine-induced itch and vasomotor responses in human skin. Br J Dermatol. 2009 Oct;161(4):737-45. doi: 10.1111/j.1365-2133.2009.09305.x. Epub 2009 May 11. — View Citation

Hallett M. How does botulinum toxin work? Ann Neurol. 2000 Jul;48(1):7-8. Review. — View Citation

Heckmann M, Heyer G, Brunner B, Plewig G. Botulinum toxin type A injection in the treatment of lichen simplex: an open pilot study. J Am Acad Dermatol. 2002 Apr;46(4):617-9. — View Citation

Heyer G, Vogelgsang M, Hornstein OP. Acetylcholine is an inducer of itching in patients with atopic eczema. J Dermatol. 1997 Oct;24(10):621-5. — View Citation

Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):249-59. Review. — View Citation

Ishikawa H, Mitsui Y, Yoshitomi T, Mashimo K, Aoki S, Mukuno K, Shimizu K. Presynaptic effects of botulinum toxin type A on the neuronally evoked response of albino and pigmented rabbit iris sphincter and dilator muscles. Jpn J Ophthalmol. 2000 Mar-Apr;44(2):106-9. — View Citation

Papoiu AD, Tey HL, Coghill RC, Wang H, Yosipovitch G. Cowhage-induced itch as an experimental model for pruritus. A comparative study with histamine-induced itch. PLoS One. 2011 Mar 14;6(3):e17786. doi: 10.1371/journal.pone.0017786. — View Citation

Reddy VB, Iuga AO, Shimada SG, LaMotte RH, Lerner EA. Cowhage-evoked itch is mediated by a novel cysteine protease: a ligand of protease-activated receptors. J Neurosci. 2008 Apr 23;28(17):4331-5. doi: 10.1523/JNEUROSCI.0716-08.2008. — View Citation

Swartling C, Naver H, Lindberg M, Anveden I. Treatment of dyshidrotic hand dermatitis with intradermal botulinum toxin. J Am Acad Dermatol. 2002 Nov;47(5):667-71. — View Citation

Unal M, Sevim S, Dogu O, Vayisoglu Y, Kanik A. Effect of botulinum toxin type A on nasal symptoms in patients with allergic rhinitis: a double-blind, placebo-controlled clinical trial. Acta Otolaryngol. 2003 Dec;123(9):1060-3. — View Citation

Wessler I, Reinheimer T, Kilbinger H, Bittinger F, Kirkpatrick CJ, Saloga J, Knop J. Increased acetylcholine levels in skin biopsies of patients with atopic dermatitis. Life Sci. 2003 Mar 28;72(18-19):2169-72. — View Citation

Wollina U, Karamfilov T. Adjuvant botulinum toxin A in dyshidrotic hand eczema: a controlled prospective pilot study with left-right comparison. J Eur Acad Dermatol Venereol. 2002 Jan;16(1):40-2. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in itch relief by VAS itch intensity reporting after 1 week, 1 month, and 3 months after treatment	The primary endpoint is to test the antipruritic effect of Botox using an itch visual analog scale (VAS) intensity scale as an outcome measure. Participants will rate itch intensity after itch is induced with cowhage.	Baseline, 1 week, 1 month, 3 months	No
Secondary	Change in heat pain relief by VAS pain intensity reporting after 1 week, 1 month, and 3 months after treatment	A secondary endpoint is to see if Botox has a relieving effect on heat pain using a pain visual analog scale (VAS) intensity scale as an outcome measure. Participants will rate pain intensity after pain is induced with a heat thermode.	Baseline, 1 week, 1 month, 3 months	No