HyperalgesiaTS-OA-CapNCT07625475
Session-Order Sensitivity of TS and OA in a Capsaicin Crossover Model
A study testing Topical 0.075% capsaicin cream (Zostrix) in people with Hyperalgesia and Pain Perception, run by University of Guelph at 1 site in Canada.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hyperalgesia, Pain Perception, Central Nervous System Sensitization
- What is being tested?
- Topical 0.075% capsaicin cream (Zostrix)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- 1 May 2024to 30 Apr 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy adult volunteers (≥18 years of age)
- Able to provide written informed consent in English
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Canada1 site
Human Health Sciences, University of Guelph
Guelph, Ontario, N1G2W1
About this study
Official title: 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.
Read the detailed description
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).
- Being tested
- Topical 0.075% capsaicin cream (Zostrix), Topical vehicle lotion (Lubriderm)
- Keywords
- temporal summation, offset analgesia, topical capsaicin, secondary hyperalgesia, quantitative sensory testing (QST), crossover trial, session-order effect, central sensitisation
- Medical subject headings
- Hyperalgesia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Topical 0.075% capsaicin cream (Zostrix)Drug
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.
Topical vehicle lotion (Lubriderm)Other
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Sequence A-to-B (Capsaicin first) | Experimental | 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. Receives: Drug: Topical 0.075% capsaicin cream (Zostrix); Other: Topical vehicle lotion (Lubriderm) |
| Arm 2: Sequence B-to-A (Vehicle first) | Active comparator | 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. Receives: Drug: Topical 0.075% capsaicin cream (Zostrix); Other: Topical vehicle lotion (Lubriderm) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mechanical temporal summation (Sumscore)
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.
Measured: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
Offset analgesia magnitude (OffA)
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.
Measured: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
Secondary outcomes (2)
Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
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.
Measured: 10, 20, 30, and 40 minutes post-intervention
Differential design-sensitivity (Measure × Intervention × Period interaction)
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.
Measured: 10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2026
- Study start1 May 2024
- Primary completion30 Apr 2025
- Study completion30 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HyperalgesiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Two-period crossover. Participants were randomised in a 1:1 intended allocation (actual 6:10) to one of two sequences (capsaicin-first or vehicle-first). Sessions were separated by a minimum 1-week washout.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Guelph
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Srbely, University of Guelph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07625475
- Sponsor's protocol ID
- GUELPH-REB-19-06-003
- Other IDs
- REB #19-06-003
- Acronym
- TS-OA-Cap
- Status last verified
- Jun 2026
- First submitted
- 22 May 2026
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 31366597Clouse JA, et al. The reliability of a temporal summation Sumscore. (2021)
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.
PubMed 11929939
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Session-order Sensitivity of Temporal Summation and Offset Analgesia in a Randomised Crossover Capsaicin Model of Secondary Hyperalgesia
- ClinicalTrials.gov ID
- NCT07625475
- Acronym / sponsor ID
- TS-OA-Cap / GUELPH-REB-19-06-003
- Keywords
- temporal summation, offset analgesia, topical capsaicin, secondary hyperalgesia, quantitative sensory testing (QST), crossover trial, session-order effect, central sensitisation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of GuelphUniversity, hospital or other
- Study start
- 1 May 2024 (actual)
- Primary completion
- 30 Apr 2025 (actual)
- Study completion
- 30 Apr 2025 (actual)
- First posted
- 4 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Two-period crossover. Participants were randomised in a 1:1 intended allocation (actual 6:10) to one of two sequences (capsaicin-first or vehicle-first). Sessions were separated by a minimum 1-week washout.
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Sequence A-to-B (Capsaicin first) | Experimental | Drug: Topical 0.075% capsaicin cream (Zostrix), Other: Topical vehicle lotion (Lubriderm)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. |
| Arm 2: Sequence B-to-A (Vehicle first) | Active comparator | Drug: Topical 0.075% capsaicin cream (Zostrix), Other: Topical vehicle lotion (Lubriderm)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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy adult volunteers (≥18 years of age)
- Able to provide written informed consent in English
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Topical 0.075% capsaicin cream (Zostrix)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. | Drug | Arm 1: Sequence A-to-B (Capsaicin first), Arm 2: Sequence B-to-A (Vehicle first) |
| Topical vehicle lotion (Lubriderm)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. | Other | Arm 1: Sequence A-to-B (Capsaicin first), Arm 2: Sequence B-to-A (Vehicle first) |
Primary outcome
Mechanical temporal summation (Sumscore)
Time frame: 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.
Offset analgesia magnitude (OffA)
Time frame: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)
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.
2 secondary outcomes
Within-session temporal stability (ICC(2,1)) of Sumscore and OffA
Time frame: 10, 20, 30, and 40 minutes post-intervention
Differential design-sensitivity (Measure × Intervention × Period interaction)
Time frame: 10, 20, 30, and 40 minutes post-intervention, across two crossover periods separated by a minimum 1-week washout.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Background: PubMed 31366597Dwan 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.
- BackgroundClouse JA, et al. The reliability of a temporal summation Sumscore. (2021)
- Background: PubMed 11929939Grill JD, Coghill RC. Transient analgesia evoked by noxious stimulus offset. J Neurophysiol. 2002 Apr;87(4):2205-8. doi: 10.1152/jn.00730.2001.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Topical 0.075% capsaicin cream (Zostrix) in people with Hyperalgesia and Pain Perception, run by University of Guelph at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mechanical temporal summation (Sumscore) (time frame: Baseline and 10, 20, 30, and 40 min post-intervention (within each of two sessions, separated by a minimum 1-week washout)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07625475, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.