Primary objective-To determine the effect of topical capsaicin on primary hyperalgesia, as assessed by the thermal heat pain test (pain detection thresholds (PDTs))-To determine the effect of topical capsaicin on the area of secondary mechanical…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Pain
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
-Pain Detection Threshold (PDT) on capsaicin treated area compared with
untreated area (°C), assessed with Q-Sense
-Area of secondary mechanical allodynia around the capsaicin treated area
(mm2), assessed with Von Frey hair stimulation
Secondary outcome
-Pain Detection Threshold (PDT) on capsaicin treated area compared with
untreated area (°C), assessed with Q-Sense
-Area of secondary mechanical allodynia around the capsaicin treated area
(mm2), assessed with Von Frey hair stimulation
-Amplitude (*V ) and latency (ms) of LEPs in primary, secondary, and control
area (N2, P2, and N2P2)
-Electrical Burst: PDT (mA), Pain Tolerance Threshold (PTT) (mA), Area Under
the VAS pain Curve (AUC) (mA*mm), and post-test VAS (mm).
-Electrical Stair (pre-cold pressor): PDT (mA), PTT (mA), Area Under the VAS
pain Curve (AUC) (mA*mm), and post-test VAS (mm).
-Electrical Stair (post-cold pressor): PDT (mA), PTT (mA), AUC (mA*mm), and
post-test VAS (mm).
-Conditioned Pain Modulation Response (change from electrical stair pre- and
post-cold pressor): PDT (mA), PTT (mA), AUC (mA*mm).
-Pressure Pain: PDT (kPa), PTT (kPa), AUC (kPa*mm), and post-test VAS (mm).
-Cold Pressor: PDT (s), PTT (s), AAC (s*mm), and post-test VAS (mm).
-Capsaicin pain - Numeric Rating Scale (NRS): Numeric Rating Scale (0-10 with
0=no pain & 10=worst pain imaginable)
-Subjective pain perception after LS on primary, secondary and control area
+LS-NRS: Numeric rating scale (0-10 with 0=no pain & 10=worst pain
imaginable)
+McGill Pain Questionnaire
Background summary
PainCart, a test battery of human evoked pain models, is able to provide
biomarkers for nociceptive and inflammatory pain at early stages of drug
development in healthy volunteers. To be able to accommodate the new analgesic
drugs that are being developed and the increasing number of novel pain
mechanisms involved, it is essential to continue optimizing and expanding the
PainCart and the evoked pain models that it consists of. As such, CHDR is
seeking to expand the PainCart with a model to robustly assess central
sensitization, by utilizing the concept of inducing secondary hyperalgesia on
an area surrounding injured, or sensitized skin.
A frequently used model to induce sensitization, is topical application of
capsaicin, the active component of hot chili peppers. This substance
selectively activates the primary nociceptive afferents of C-fibers and
multimodal A*-fibers via the Transient Receptor Potential cation channel
subfamily V member 1 (TRPV1) receptor. Topical application of capsaicin and its
effects on sensitization have been explored in previous CHDR studies (CHDR1703,
CHDR1738, CHDR1738-D). Preliminary results of CHDR1703 suggest that the current
formulation (capsaicin 1% cream) does indeed induce peripheral sensitization,
as observed with altered heat pain detection thresholds (PDT*s) on the primary
(treated) area. However, the cream does not induce the co-expected central
sensitization, as assessed by laser evoked potentials (LEP*s) and von Frey
filaments on the secondary area (site surrounding treated area). Literature
suggests that a different formulation may increase the latter sensitizing
effect, due to superior penetration of capsaicin through the skin. The proposed
study therefore aims to validate the use of a different formulation of
capsaicin for topical application (a 1% ethanolic solution), to assess
allodynia and (secondary) hyperalgesia, as an extension to CHDR*s PainCart test
battery.
To quantify the effects of pain in the context of this updated model, both
psychophysical (using the McGill Pain Questionnaire) and physiological
parameters (LEPs and heat PDT*s) will be investigated. The painful stimuli to
the primary area will be induced by a laser stimulation (LS) and thermal heat
pain. During LS, electroencephalography (EEG) will be used to record laser
LEP*s on both the primary and secondary area. Heat PDT*s will be assessed on
the primary area, to confirm peripheral sensitization. In addition, the area of
primary and secondary hyperalgesia will be assessed using mechanical
stimulation with von Frey filaments.
Study objective
Primary objective
-To determine the effect of topical capsaicin on primary hyperalgesia, as
assessed by the thermal heat pain test (pain detection thresholds (PDTs))
-To determine the effect of topical capsaicin on the area of secondary
mechanical allodynia, as assessed with Von Frey filaments (mm2)
Secondary objectives
-To determine the feasibility of measuring secondary hyperalgesia using LEPs
-To determine the intra-individual reproducibility of primary and secondary
hyperalgesia/ allodynia measurements with Von Frey, LEPs and thermal heat pain.
-To assess the feasibility of incorporating the topical 1% ethanolic capsaicin
pain model in the PainCart test battery
-To evaluate the effect of capsaicin application on psychophysical,
electrophysiological and PainCart parameters
Exploratory objectives
-To explore the effects of capsaicin on the skin by optical coherence
tomography, clinical photography, laser speckle contrast imaging, and thermal
imaging
Study design
This will be an open-label single-dose proof-of-Concept study. Subjects will
attend the clinic on 2 occasions that both consist of one full study day, with
a wash-out period in between occasions of 7 (±2) days. Subjects will be
contacted 7±2 days after the last capsaicin administration, for a follow-up
telephone call.
Intervention
50uL of 1% capsaicin in ethanolic solution applied topically on the volar
forearm
Study burden and risks
The risks associated in this study can be divided into topical capsaicin and
LS-related risks.
Topical capsaicin
Topical capsaicin can lead to both sensitization and defunctionalization of
TRPV1 containing nerve fibres, depending on the concentration and application
frequency. Sensitization could result in transient burning sensations,
hyperalgesia, allodynia and erythema. Defunctionalization due to
overstimulation could result in increased tactile and nociceptive thresholds,
after application of highly concentrated capsaicin products (8%). Both
consequences are reversible in respectively hours and weeks. In addition, as
mentioned in 1.3.1 of the protocol, nerve defunctionalization is not expected
in this study, given the eightfold lower dose.
LS
Repeated application of LS on the exact same location within minutes (Plaghki &
Mouraux, 2003) may induce a risk of skin burning. Therefore, in this study the
location of stimulation is varied within every stimulation block of multiple
stimulations. In addition, the laser energy has been limited to 2 J with a
diameter of 5 mm to prevent skin damage. For more information on the
stimulation method, please see Section 7.1. of the protocol.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Healthy male subjects, 18 to 45 years of age, inclusive. Healthy status is defined by absence of evidence of any active or chronic disease following a detailed medical and surgical history, a complete physical examination including vital signs. ;2. Body mass index (BMI) between 18 and 30 kg/m2, inclusive. ;3. Able to participate and willing to give written informed consent and to comply with the study restrictions.
Exclusion criteria
1. History or symptoms of any significant disease including (but not limited to), neurological, psychiatric, endocrine, cardiovascular, respiratory, gastrointestinal, hepatic, or renal disorder. ;2. Clinically significant abnormalities, as judged by the Investigator, in laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis). In the case of uncertain or questionable results, tests performed during screening may be repeated before randomization to confirm eligibility or judged to be clinically irrelevant for healthy subjects. ;3. History of alcohol or drug abuse;4. Participation in an investigational drug or device study within 3 months prior to screening. ;5. Any confirmed significant allergic reactions (urticaria or anaphylaxis) after previous exposure to capsaicin ;6. Subject indicating intolerable pain after capsaicin administration at screening;7. Any current, clinically significant, known medical condition in particular any existing conditions that would affect sensitivity to cold (such as atherosclerosis, Raynaud*s disease, urticaria, hypothyroidism) or pain (i.e., disease that causes pain, hypesthesia, hyperalgesia, allodynia, paraesthesia, neuropathy) ;8. Subjects indicating pain tests intolerable at screening or achieving tolerance at >80% of maximum input intensity for any pain test for cold, pressure and electrical tests.;9. Dark skin (Fitzpatrick skin type V - VI), wide-spread acne, tattoos or scarring on the volar forearms.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL68698.056.19 |