Session-Order Sensitivity of TS and OA in a Capsaicin Crossover Model (TS-OA-Cap)
3. června 2026 aktualizováno: John Srbely, University of Guelph
Session-order Sensitivity of Temporal Summation and Offset Analgesia in a Randomised Crossover Capsaicin Model of Secondary Hyperalgesia
Temporal summation (TS) and offset analgesia (OA) are widely used psychophysical endpoints in pain research that index different components of central nociceptive processing.
While crossover designs are commonly used in experimental pain studies to reduce between-participant variability, the design-stability of these endpoints under repeated testing during experimental sensitisation is not well characterised.
This study compared the design-stability of mechanical TS (Sumscore) and offset analgesia magnitude (OffA) in a two-period, vehicle-controlled crossover trial of capsaicin-evoked secondary hyperalgesia in healthy adults.
The primary aim was methodological: to determine whether session-order effects differ between TS and OffA when these are used as outcome measures in two-period crossover designs of capsaicin-induced central sensitisation.
Topical capsaicin was used as a reversible experimental intervention to create a controlled, transient state of secondary hyperalgesia rather than as a therapeutic intervention.
The study informs endpoint selection in future quantitative sensory testing (QST) crossover trials.
Přehled studie
Postavení
Dokončeno
Detailní popis
This was a single-site, two-period, vehicle-controlled, allocation- and formulation-blinded, randomised crossover study conducted at the Department of Human Health Science, University of Guelph, Canada.
Sixteen healthy adult volunteers (10 female, 6 male; mean age 21.9 years) were recruited between May 2024 and April 2025.
Participants were randomised in a 1:1 intended allocation to one of two sequences: capsaicin-first then vehicle (Sequence A-to-B) or vehicle-first then capsaicin (Sequence B-to-A); actual allocation was 6:10.
The allocation sequence was computer-generated by a research assistant not involved in outcome collection.
Sessions were separated by a minimum 1-week washout.
Topical 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal) was applied as a 5 mL dose to a 5 x 10 cm target area on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes.
The comparator was an equivalent 5 mL volume of inert vehicle lotion (Lubriderm; Johnson & Johnson) applied identically; creams were matched for colour and texture and prepared by a research assistant in unlabelled containers.
Mechanical temporal summation (Sumscore; 256 mN pinprick, 16 stimuli at 1 Hz) and thermal offset analgesia (OA; 32-46°C stepped-stimulus protocol with three thermal hold durations of 5, 10, and 15 s) were assessed at baseline and at 10, 20, 30, and 40 min post-intervention.
Continuous pain ratings during thermal stimulation were captured via CoVAS.
Primary outcomes (Sumscore and the duration-averaged baseline-normalised OffA) were analysed using REML linear mixed-effects models with fixed effects for Intervention, Time, Intervention x Time, Period, and Sequence, with random intercepts for Participant; sex was included as a pre-specified covariate.
Within-session temporal stability was assessed using ICC(2,1).
A combined Measure x Intervention x Period model tested for differential design-sensitivity between TS and OffA.
The study was approved by the University of Guelph Research Ethics Board (REB #19-06-003).
Typ studie
Intervenční
Zápis (Aktuální)
16
Fáze
- Nelze použít
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Ontario
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Guelph, Ontario, Kanada, N1G2W1
- Human Health Sciences, University of Guelph
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ano
Popis
Inclusion Criteria:
- Healthy adult volunteers (≥18 years of age)
- Able to provide written informed consent in English
Exclusion Criteria:
- Current or chronic pain
- Neurological disease
- Skin conditions or sensitivity over the test sites to capsaicin
- Contraindications to thermal stimulation of the skin
- Musculoskeletal conditions that could alter somatosensory processing
- Use of analgesic medications within 24 hours prior to each session
- Use of caffeine within 24 hours prior to each session
- Use of alcohol within 24 hours prior to each session
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Základní věda
- Přidělení: Randomizované
- Intervenční model: Crossover Assignment
- Maskování: Trojnásobný
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: Arm 1: Sequence A-to-B (Capsaicin first)
Participants received topical 0.075% capsaicin (Zostrix) cream (5 mL) in Period 1, followed by topical inert (Lubriderm) vehicle (5 mL) in Period 2. Periods were separated by a minimum 1-week washout.
n = 6.
|
5 mL of 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal, Amityville, NY, USA) applied to a 5 x 10 cm target region on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes (total 15 mL).
The cream was massaged into the skin by a gloved investigator until no residue was visible.
Used as an experimental probe to evoke transient, reversible secondary hyperalgesia; not under therapeutic evaluation.
5 mL of inert vehicle lotion (Lubriderm; Johnson & Johnson, Montgomery, NJ, USA) applied to the same dermatomes as the capsaicin condition (total 15 mL), using the identical preparation and massage technique.
Matched to the capsaicin cream for colour and texture.
|
|
Aktivní komparátor: Arm 2: Sequence B-to-A (Vehicle first)
Participants received topical inert (Lubriderm) vehicle (5 mL) in Period 1, followed by topical 0.075% capsaicin (Zostrix) cream (5 mL) in Period 2. Periods were separated by a minimum 1-week washout.
n = 10.
|
5 mL of 0.075% capsaicin cream (Zostrix; Hi-Tech Pharmacal, Amityville, NY, USA) applied to a 5 x 10 cm target region on the lateral elbow and to bilateral C5-C6 cervicothoracic dermatomes (total 15 mL).
The cream was massaged into the skin by a gloved investigator until no residue was visible.
Used as an experimental probe to evoke transient, reversible secondary hyperalgesia; not under therapeutic evaluation.
5 mL of inert vehicle lotion (Lubriderm; Johnson & Johnson, Montgomery, NJ, USA) applied to the same dermatomes as the capsaicin condition (total 15 mL), using the identical preparation and massage technique.
Matched to the capsaicin cream for colour and texture.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Mechanical temporal summation (Sumscore)
Časové okno: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
|
Sumscore is a summed pinprick temporal-summation response computed from a train of 16 repeated 256 mN pinprick stimuli delivered perpendicularly to the skin at 1 Hz, paced by a metronome.
Pain ratings (NPRS 0-10) immediately after each stimulus were summed (Clouse et al., 2021).
The primary Sumscore endpoint was pre-specified as the average of the lateral and inferior testing sites at the lateral elbow, expressed as a baseline-normalised ratio.
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Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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Offset analgesia magnitude (OffA)
Časové okno: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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OffA was measured during a three-phase stepped-stimulus thermal protocol (32-45-46-45-32°C; T1/T2/T3 phases) using a 32 x 32 mm Peltier contact thermode (TSA-II NeuroSensory Analyzer, Medoc AMS).
Continuous pain ratings were collected via CoVAS (0-100) at 10 Hz.
OA magnitude was quantified as peak minus nadir CoVAS during the 46°C hold and the subsequent 45°C phase.
The primary OffA endpoint was pre-specified as the duration-averaged value across three thermal hold durations (5, 10, and 15 s at 46°C), expressed as a baseline-normalised ratio.
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Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
Časové okno: 10, 20, 30, and 40 minutes post-intervention
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Intraclass correlation coefficient (ICC(2,1); Shrout and Fleiss, 1979) computed across the four post-intervention time points (10, 20, 30, 40 min) within each intervention condition, separately for Sumscore and OffA.
Reported with bias-corrected bootstrap 95% confidence intervals.
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10, 20, 30, and 40 minutes post-intervention
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Differential design-sensitivity (Measure × Intervention × Period interaction)
Časové okno: 10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
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A combined linear mixed-effects model using within-measure z-scored outcomes tested whether the period-adjusted intervention estimate differed between TS and OffA.
Three-way Measure x Intervention x Period interaction tested via Wald F-tests with residual degrees of freedom.
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10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Publikace a užitečné odkazy
Osoba odpovědná za zadávání informací o studiu tyto publikace poskytuje dobrovolně. Mohou se týkat čehokoli, co souvisí se studiem.
Obecné publikace
- Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol. 2002 Apr;87(4):2205-8. doi: 10.1152/jn.00730.2001.
- Dwan K, Li T, Altman DG, Elbourne D. CONSORT 2010 statement: extension to randomised crossover trials. BMJ. 2019 Jul 31;366:l4378. doi: 10.1136/bmj.l4378.
- Clouse JA, et al. The reliability of a temporal summation Sumscore. (2021)
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
1. května 2024
Primární dokončení (Aktuální)
30. dubna 2025
Dokončení studie (Aktuální)
30. dubna 2025
Termíny zápisu do studia
První předloženo
22. května 2026
První předloženo, které splnilo kritéria kontroly kvality
3. června 2026
První zveřejněno (Aktuální)
4. června 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
4. června 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
3. června 2026
Naposledy ověřeno
1. června 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Neurologické projevy
- Nemoci nervového systému
- Poruchy vnímání
- Somatosenzorické poruchy
- Patologické stavy, příznaky a symptomy
- Příznaky a symptomy
- Hyperalgezie
- Organické chemikálie
- Heterocyklické sloučeniny
- Mastné kyseliny
- Lipidy
- Alkeny
- Uhlovodíky, acyklické
- Uhlovodíky
- Uhlovodíky, cyklické
- Alkaloidy
- Uhlovodíky, aromatické
- Amidy
- Katecholy
- Fenoly
- Deriváty benzenu
- Mastné kyseliny, nenasycené
- Solanaceous alkaloidy
- Polynenasycené alkamidy
- Mastné kyseliny, mononenasycené
- Kapsaicin
Další identifikační čísla studie
- GUELPH-REB-19-06-003
- REB #19-06-003 (Jiný identifikátor: University of Guelph)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
De-identified individual participant data (IPD) and statistical analysis code will be available from the corresponding author on reasonable request, subject to a data-use agreement and institutional ethics/data-sharing requirements.
Materials required to reproduce the intervention and assessment protocol are described in the published Methods and Supplementary Materials.
Časový rámec sdílení IPD
On request following publication of the primary manuscript.
Kritéria přístupu pro sdílení IPD
Reasonable request to the corresponding author for non-commercial research use, subject to a data-use agreement consistent with University of Guelph data-sharing policy.
Typ podpůrných informací pro sdílení IPD
- PROTOKOL STUDY
- MÍZA
- ICF
- ANALYTIC_CODE
Informace o lécích a zařízeních, studijní dokumenty
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