Phase I Methodology Study to Validate the Cantharidin Blister Model in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01762787
First received: November 28, 2012
Last updated: January 7, 2013
Last verified: January 2013
  Purpose

The purpose of this study is to refine the cantharidin-induced blister assay in healthy volunteers as a model of inflammatory disease. The study is an experimental trial in healthy volunteers in two parts; Part 1 to optimise the model and Part 2 to validate using two anti-inflammatory treatments with different modes of action.


Condition Intervention Phase
Inflammation
Drug: Cantharidin solution
Drug: Aspirin
Drug: Prednisolone
Drug: Placebo to aspirin
Drug: Placebo to prednisolone
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Crossover Assignment
Masking: Single Blind (Subject)
Official Title: A Randomised, Single Blind, Placebo-Controlled, Cross-over, Phase 1 Methodology Study to Validate the Cantharidin Blister Model in Healthy Male Volunteers

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Blister volume of fluid [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Volume of fluid extracted from blisters induced by cantharidin application

  • Cell population in blister fluid [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages

  • Inflammatory mediators in blister fluid [ Time Frame: 48 hours ] [ Designated as safety issue: No ]
    Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.


Secondary Outcome Measures:
  • Blister volume of fluid [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Volume of fluid extracted from blisters induced by cantharidin application

  • Cell population in blister fluid [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Flow cytometry performed on cells from blister fluid including measurement of some or all of the following parameters: CD45, CD16, CD14, cell viability, CD206, CD64 or CD84, apoptosis, total blister leukocytes (CD45+), monocytes (CD14+), neutrophils (CD16 high), monocyte/macrophage like cells (CD64+ or CD84+); subsets of these cells that are undergoing apoptosis; subsets of monocyte/macrophages

  • Inflammatory mediators in blister fluid [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Inflammatory mediators in blister fluid, measured by immunoassay as primary endpoints may include (but will not be limited to): MPO, IL-10, IL-8, IL-6, IL-1β, TNF-α, LTB4.

  • Numbers and types of leukocytes in blood, and inflammatory mediators in plasma [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
  • Blister healing/skin appearance at 6 week follow up [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: August 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Effect of Aspirin
Positive control as previously used in the cantharidin blister experimental model of inflammation
Drug: Cantharidin solution
5 microlitres of 0.025 to 0.5% topically on Day 1, 2 and 3
Drug: Aspirin
300mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only
Drug: Placebo to aspirin
0mg three times daily orally over a course of 4 days (starting Day -3) Part 2 only
Experimental: Effect of steroid - Prednisolone
Prednisolone selected as steroids should provide the most robust positive control anti-inflammatory therapy
Drug: Cantharidin solution
5 microlitres of 0.025 to 0.5% topically on Day 1, 2 and 3
Drug: Prednisolone
30mg orally once a day over a course of 4 days (starting Day -3) Part 2 only
Drug: Placebo to prednisolone
0mg orally once a day over a course of 4 days (starting Day -3) Part 2 only
Experimental: Cantharidin exposure to optimise blister formation
Cantharidin exposure to optimise blister formation
Drug: Cantharidin solution
5 microlitres of 0.025 to 0.5% topically on Day 1, 2 and 3

Detailed Description:

The purpose of this study is to refine the cantharidin-induced blister assay. The cantharidin-induced skin blister assay may be a valuable tool for evaluation of the pharmacodynamic effects of novel anti-inflammatory drugs in healthy volunteers, particularly for novel concepts targeting neutrophilic or monocytic inflammation. The study is an experimental trial in healthy volunteers for the purpose of evaluating the variability (between subjects and within subject) of the size and contents (cellular and fluid) of blisters induced on the forearm by direct application of cantharidin. Specifically, the aim is to assess whether variability is reduced in the current study, in which cantharidin will be applied directly to the skin in order to minimise the variation in total skin exposure. Once experimental design has been optimised then Part 2 of the study will examine the effects of a course of anti-inflammatory treatment prior to induction of blisters on the size and/or contents of blisters in a single blind crossover protocol.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, vital signs, complete blood count and clinical chemistry. A subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures
  • Male between 18 and 55 years of age inclusive, at the time of signing the informed consent
  • Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

Exclusion Criteria:

  • Subjects with very fair or very dark skin type
  • Presence on either forearm of tattoos, naevi, scars, keloids, hyperpigmentation, excessive hair or any skin abnormalities that may, in the opinion of the Investigator, interfere with study assessments
  • Subjects with a history of keloids, skin allergy, hypersensitivity or contact dermatitis, including previous reactions to dressings to be used in the study
  • Subjects with a history of lymphangitis and/or lymphoedema
  • Subjects with a history of HIV infection, hepatitis B or C
  • A positive pre-study drug/alcohol screen
  • Use of prescription or non-prescription drugs, including ergot derivatives e.g. dihydroergotamine (Dihydergot), vitamins, herbal and dietary supplements (including St John's Wort) within whichever is the longer period of 7 days or 5 half-lives (if known) prior to the first challenge day, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the dosing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer)
  • Where participation in the study would result in donation of blood or blood products in excess of 500 mL within 56-day period For Part 2 only
  • History of previous peptic ulcers, gastritis, GI bleed or history of bleeding problems, e.g. haemorrhoids or spontaneous nose bleeds
  • Subjects with a history of asthma
  • For aspirin only: History of sensitivity to aspirin or non steroidal anti-inflammatory drugs or a history of drug or other allergy that, in the opinion of the Investigator or GSK Medical Monitor contraindicates their participation
  • For prednisolone only: Subjects with systemic infections, hypersensitivity to any formulation ingredient, or ocular herpes simplex will be excluded. Those with, or a previous history of, tuberculosis, hypertension, congestive heart failure, liver failure, renal insufficiency, diabetes mellitus or in those with a family history of diabetes, osteoporosis, glaucoma or in those with a family history or glaucoma, subjects with a history of severe affective disorders and particularly those with a previous history of steroid-induced psychoses (in themselves or first degree relatives), epilepsy, peptic ulceration or previous steroid myopathy will also be excluded
  • For prednisolone only: if a subject has not had chicken pox previously
  • For prednisolone only: no live vaccines to be administered within 3 months of last prednisolone dose
  • Subjects with a history of diabetes and peripheral vascular disease
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01762787

Locations
United Kingdom
GSK Investigational Site
Cambridge, United Kingdom, CB2 2GG
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01762787     History of Changes
Other Study ID Numbers: 114416
Study First Received: November 28, 2012
Last Updated: January 7, 2013
Health Authority: United Kingdom: Research Ethics Committee

Additional relevant MeSH terms:
Inflammation
Pathologic Processes
Aspirin
Methylprednisolone acetate
Prednisolone acetate
Prednisolone
Methylprednisolone
Methylprednisolone Hemisuccinate
Cantharidin
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics

ClinicalTrials.gov processed this record on August 18, 2014