Clinical trial NCT02639052: Itch Relieving Effect of Botox: a Study in Healthy Subjects
Official title: Itch Relieving Effect of Botox: a Study in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Pruritus
Keywords: Itch
Botox
Healthy Volunteers
Lead sponsor: Temple University
Sponsor class: OTHER
Collaborators: name: Allergan
First posted: 2015-12-24
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Itch by VAS Itch Intensity at Baseline (Visit 1)
timeFrame: Baseline (Visit 1)
measure: Itch by VAS Itch Intensity at 1 Week (Visit 2)
timeFrame: 1 week from Baseline
measure: Itch by VAS Itch Intensity at 1 Month (Visit 3)
timeFrame: 1 Month from Baseline
measure: Itch by VAS Itch Intensity at 3 Months (Visit 4)
timeFrame: 3 Months from Baseline
Secondary outcomes:
measure: Change in Heat Pain Relief by VAS Pain Intensity Reporting After 1 Week, 1 Month, and 3 Months After Treatment
timeFrame: Baseline, 1 week, 1 month, 3 months
Other outcomes:
Locations:
Study officials:
affiliation: Temple University
name: Gil Yosipovitch, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang W, Foster JA, Rogachefsky AS. Pharmacology of botulinum toxin. J Am Acad Dermatol. 2000 Aug;43(2 Pt 1):249-59. doi: 10.1067/mjd.2000.105567.
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citation: 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. doi: 10.1016/j.pain.2003.10.008.
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. doi: 10.1046/j.1468-3083.2002.00361.x.
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. doi: 10.1067/mjd.2002.124605.
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. doi: 10.1067/mjd.2002.120455.
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. doi: 10.1080/00016480310000755.
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.
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. doi: 10.1111/j.1346-8138.1997.tb02305.x.
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. doi: 10.1016/s0024-3205(03)00079-1.
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.
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.