Acute PainNCT07549490
Human Experimental Models of Pain (HEMP)
A study testing Naproxen and Pregabalin in people with Acute Pain, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
Trial summary
This pilot study will test an innovative way to establish how pain medicines provide analgesia in healthy adults. The study uses a group of short, controlled pain tests to look at different types of pain responses in the body. Read more about this study
- Who is it for?
- Ages 18 to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Acute Pain
- What is being tested?
- Naproxen and Pregabalin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2026to 31 Dec 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 100 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- For an individual to be eligible to participate in this study, they must meet all of the following criteria:
- Voluntarily consent to participate and provide written informed consent prior to the start of any study-specific procedures.
- Read and speak English fluently.
- State willingness to comply with all study procedures and availability for the duration of the study.
- Are not pregnant or breastfeeding.
- Are 18 or older years of age at screening.
Show all 12Show fewer
- Have a skin type score between 2 and 5 (inclusive) on the Fitzpatrick Scale.
- Must correctly identify at least nine out of 12 temperatures (32 degrees Celsius, 38 degrees Celsius, 44 degrees Celsius, and 50 degrees Celsius, each presented three times) during the sensory discrimination test at screening.
- Provide a verbal pain rating between 4 and 9 (inclusive) during the intradermal capsaicin challenge at screening. The study team will verify tolerability, and participants will continue only after it has been confirmed.
- During the cold pressor test at screening, provide a verbal pain rating between 4 and 9 (inclusive) and keep one hand completely immersed in ice-cold water (1-4 degrees Celsius) between 1 and 4 minutes (inclusive). The study team will verify tolerability, and participants will continue only after it has been confirmed.
- Are able to learn and perform all quantitative sensory testing QST procedures (see the separate QST manual).
- Have the ability to take oral medication and be willing to adhere to the study intervention regimen.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Have a history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the participant or the validity of the study results.
- Have alcohol or drug dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM IV-TR) and/or participants who have ever been in a substance or alcohol rehabilitation program to treat their substance dependence are currently seeking such treatment.
- Have a clinically significant abnormal finding on the physical exam, medical history, or clinical laboratory results at screening.
- Have a history of psychotic reactions, a non-psychotic emotional disorder, or another mental illness that, in the opinion of the investigator, may affect the ability of the participant to participate in the study.
- Have recent history of suicidal ideation or suicidal behavior within the past 6 months, as assessed by the Columbia- Suicide Severity Rating Scale (C-SSRS) at screening (baseline version) or at check-in ( Since Last Visit version).
Show all 17Show fewer
- Have a history of allergy or hypersensitivity to pregabalin or other gabapentinoids, naproxen or other NSAIDs, or another ingredient in the study drugs, or anything else that, in the opinion of the Investigator, could put the participant at risk.
- Have participated in another clinical trial (randomized participants only) within 30 days prior to the first dose of study medication.
- Use any prescription medication, except hormonal contraceptive or hormonal replacement therapy, from 14 days prior to the first dose of study medication until study participation has ended without evaluation and approval by the Investigator.
- Donate blood or plasma within 30 days prior to the first dose of study medication until the end of study participation. It is recommended that participants not donate blood or plasma until at least 30 days after their study participation has ended.
- Female participants who are currently pregnant or breastfeeding, or who are planning to become pregnant during the study or within 30 days after the last study drug administration.
- Show a positive urine alcohol test at screening.
- Have smoked or used tobacco- or nicotine-containing products within 30 days prior to the first dose of study treatment until the end of the study.
- Have an allergy to capsaicin or another capsaicinoid.
- Have a tattoo, excessive scarring or discoloration, keloid formation, or, at the Investigator s discretion, otherwise unhealthy skin (e.g., eczema, psoriasis, burn, and cut) at a QST site.
- Have a significant history of nerve injury or damage at a QST site, at the Investigator s discretion.
- Participants who report any stimulus as intolerable at any point during the screening procedures will be excluded from participation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: A Pilot Study for Developing a Comprehensive Signal Detection Approach for the Mechanisms of Action and Analgesic Efficacy of Two Analgesics Using Human Experimental Models of Pain (HEMP)
This pilot study will test an innovative way to establish how pain medicines provide analgesia in healthy adults. The study uses a group of short, controlled pain tests to look at different types of pain responses in the body. The main goal is to find out if this testing approach can show the pain-relieving effects of 2 medicines, pregabalin and naproxen versus placebo, and show how they provide relief of different types of pain.
The study hypothesis is that this pain testing approach administered as a battery would be able to tell the difference between a medicine that works mainly in the brain and spinal cord (pregabalin) and a medicine that works mainly on inflammation in body tissues (naproxen).
Read more
Up to 25 healthy adults will take part. Each participant will receive all 3 study treatments, pregabalin, naproxen, and placebo, administered in random order during separate study periods. The order will be assigned by chance. Neither the participant nor the study team will know which treatment is given at each visit.
The study includes several experimental pain tests. These include:
a heat and capsaicin skin test that causes short-term skin sensitivity,
a UVB light test that causes a temporary sunburn-like sensitivity, and
a cold pressor test, in which a hand is placed in very cold water for a short time.
Participants will also have sensory testing to measure how they feel touch, pressure, pinprick, warmth, heat, and cold. Blood samples will be collected to measure study drug levels. Urine samples, vital signs, and other safety checks will also be done.
Each treatment visit includes testing before and for several hours after taking the study drug. There will be a washout period of at least 48 hours between treatments. Total participation may last up to about 10 weeks.
This study is not expected to provide direct medical benefit to participants. The information learned may help researchers improve early testing of future pain treatments....
Read the detailed description
Study Description:
This pilot study is designed to validate the performance characteristics of HEMP. This pilot study is a single-center, randomized, double-blind, three-period, three-treatment crossover designed to investigate how well the HEMP model distinguishes the analgesic properties of two medications, one which acts centrally and the other one acts peripherally.
Up to 25 healthy adults will be enrolled in this study, which will consist of a screening phase and a treatment phase with three periods. Participants will be randomly assigned to receive either a gabapentinoid (pregabalin), a non-steroidal anti-inflammatory drug (NSAID) (naproxen), or a placebo during each period of the treatment phase (see Table 2 for the study drugs). Each dose will be separated by a wash-out period of at least 48 hours.
Assessments will be performed at baseline and over a period of 8 hours following each drug administration to establish pharmacodynamic, pharmacokinetic, and safety properties of the treatments.
Objectives:
Primary Objective:
To establish the ability of HEMP to demonstrate the analgesic efficacy of pregabalin and naproxen based on their known mechanisms of action (central vs. peripheral, respectively) as measured by the severity of experimental pain, allodynia, and hyperalgesia across three pain models.
Secondary Objectives:
To demonstrate that HEMP can determine factors that differentiate responders from non-responders to the study drugs, when evaluating their analgesic properties of these drugs in humans.
Endpoints:
Pharmacodynamics (PD) Primary Endpoint:
- Change from baseline in pain intensity (PI) visual analog scale (VAS) score for allodynia (soft brush) after first heat/capsaicin application (HCM)
- Change from baseline in PI VAS score for hyperalgesia (pin-prick) after first HCM
- Change from baseline in PI VAS score for hyperalgesia (pin-prick) ultraviolet (UVB) light exposure.
- Change from baseline in PI VAS score for heat hyperalgesia (thermal-heat pain) UVB
- Change from baseline in PI VAS score after hand removal in Cold Pressor Test (CPT), i.e., cold water immersion
Secondary Endpoints:
- Weighted mean (based on area under the curve (AUC)) VAS score for spontaneous pain over 0-60 mins following first and second HCM.
- Area of secondary hyperalgesia to pin-pick after HCM following first and second HCM
- Change from baseline in PI VAS score for thermal-heat hyperalgesia following first and second HCM
- Proportion of participant who had at least 30% reduction in PI VAS scores from baseline after a Quantitative Sensory Testing (QST) measure (soft brush, light pressure, pin-prick, thermal contact- warm, thermal contact-heat pain, cold) after first and second HCM and UVB PK parameters (e.g., AUClast, Clast, Cmax, tmax)
- Conditions
- Acute Pain
- Being tested
- Placebo, Naproxen, Pregabalin
- Keywords
- Human Experimental Models of Pain, HCM (Heat/Capsaicin Pain Model), Pain Mechanisms
- Medical subject headings
- Acute Pain, Cardiomyopathy, Hypertrophic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Over-encapsulated matching placebo administered as a single oral dose in one treatment period of this randomized, double-blind, 3-period crossover study. The placebo is made to look identical to active study drug capsules to maintain blinding. Each participant receives placebo once, with at least 48 hours washout between treatment periods.
NaproxenDrug
Over-encapsulated oral naproxen, 550 mg, administered as a single dose in one treatment period of this randomized, double-blind, 3-period crossover study. Each participant receives naproxen once, with at least 48 hours washout between treatment periods.
PregabalinDrug
Over-encapsulated oral pregabalin, 300 mg, administered as a single dose in one treatment period of this randomized, double-blind, 3-period crossover study. Each participant receives pregabalin once, with at least 48 hours washout between treatment periods.
| Study group | Role | What they receive |
|---|---|---|
| Sequence ABC (Pregabalin - Naproxen - Placebo) | Experimental | Participants assigned to this sequence will receive single-dose oral pregabalin 300 mg in Period 1, naproxen 550 mg in Period 2, and matching placebo in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
| Sequence ACB (Pregabalin - Placebo - Naproxen) | Experimental | Participants assigned to this sequence will receive single-dose oral pregabalin 300 mg in Period 1, matching placebo in Period 2, and naproxen 550 mg in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
| Sequence BAC (Naproxen - Pregabalin - Placebo) | Experimental | Participants assigned to this sequence will receive single-dose oral naproxen 550 mg in Period 1, pregabalin 300 mg in Period 2, and matching placebo in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
| Sequence BCA (Naproxen - Placebo - Pregabalin) | Experimental | Participants assigned to this sequence will receive single-dose oral naproxen 550 mg in Period 1, matching placebo in Period 2, and pregabalin 300 mg in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
| Sequence CAB (Placebo - Pregabalin - Naproxen) | Experimental | Participants assigned to this sequence will receive matching placebo in Period 1, pregabalin 300 mg in Period 2, and naproxen 550 mg in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
| Sequence CBA (Placebo - Naproxen - Pregabalin) | Experimental | Participants assigned to this sequence will receive matching placebo in Period 1, naproxen 550 mg in Period 2, and pregabalin 300 mg in Period 3. Treatment periods are separated by at least 48 hours. Receives: Drug: Placebo; Drug: Naproxen; Drug: Pregabalin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in pain intensity after cold pressor test
Change from baseline in participant-rated pain intensity VAS score measured immediately after hand removal from cold water during the cold pressor test (CPT). Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in pain intensity for allodynia (soft brush) after first heat/capsaicin pain model application
Change from baseline in participant-rated pain intensity VAS score for soft-brush allodynia at the heat/capsaicin pain model (HCM) site after the first HCM application. Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in pain intensity for hyperalgesia (pin-prick) after first heat/capsaicin pain model application
Change from baseline in participant-rated pain intensity VAS score for pin-prick hyperalgesia at the HCM site after the first HCM application. Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in pain intensity for mechanical hyperalgesia (pin-prick) at the UVB site
Change from baseline in participant-rated pain intensity VAS score for pin-prick hyperalgesia at the UVB-treated skin site. Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in pain intensity for thermal hyperalgesia (heat pain) at the UVB site
Change from baseline in participant-rated pain intensity VAS score for thermal-heat pain hyperalgesia at the UVB-treated skin site. Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Secondary outcomes (5)
Weighted mean pain intensity VAS score for spontaneous pain over 0 to 60 minutes following first and second HCM applications
Weighted mean spontaneous pain visual analog scale (VAS) score calculated using area under the curve (AUC) over 60 minutes after each HCM application. Higher scores indicate greater spontaneous pain.
Measured: 0 to 60 minutes after the first and second HCM applications during each treatment period
Area of secondary hyperalgesia to pin-prick following first and second HCM applications
Size of the mapped area of secondary pin-prick hyperalgesia at the HCM site after each HCM application. Larger area indicates greater secondary hyperalgesia.
Measured: After the first and second HCM applications during each treatment period
Change from baseline in pain intensity VAS score for thermal-heat hyperalgesia following first and second HCM applications
Change from baseline in participant-rated pain intensity VAS score for thermal-heat pain hyperalgesia at the HCM site after first and second HCM applications. Higher scores indicate greater pain intensity.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Proportion of participants with at least 30% reduction from baseline in pain intensity VAS score after QST measures at HCM and UVB sites
Proportion of participants with at least 30% reduction from baseline in pain intensity VAS score after quantitative sensory testing (QST) modalities, including soft brush, light pressure, pin-prick, warm, heat pain, and cold, at HCM and UVB sites.
Measured: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Pharmacokinetic parameters of pregabalin and naproxen
Plasma pharmacokinetic parameters, including AUClast, Clast, Cmax, and Tmax, for pregabalin and naproxen.
Measured: Predose and 30, 90, 180, 240, 360, and 420 minutes after dosing in each active treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2026
- Study start8 Nov 2026 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute PainStudies 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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Miroslav Backonja, M.D., Principal investigator, National Center for Complementary and Integrative Health (NCCIH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07549490
- Sponsor's protocol ID
- 10002450
- Other IDs
- 002450-AT
- Status last verified
- 20 Apr 2026
- First submitted
- 23 Apr 2026
- Last updated
- 3 Nov 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data underlying the results reported for this study may be shared upon request after completion of the primary endpoints. This may include baseline demographic and eligibility data, treatment sequence/assignment, pharmacodynamic data from the HEMP procedures and quantitative sensory testing (including VAS pain ratings from HCM, UVB, and cold pressor testing), pharmacokinetic concentration data and derived PK parameters, and safety data such as adverse events, vital signs, and clinical laboratory results. Data sharing will be handled by the PI or designee in accordance with NIH policies and applicable IRB/privacy requirements.
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study for Developing a Comprehensive Signal Detection Approach for the Mechanisms of Action and Analgesic Efficacy of Two Analgesics Using Human Experimental Models of Pain (HEMP)
- ClinicalTrials.gov ID
- NCT07549490
- Acronym / sponsor ID
- 10002450
- Conditions
- Acute Pain
- Keywords
- Human Experimental Models of Pain, HCM (Heat/Capsaicin Pain Model), Pain Mechanisms
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- National Center for Complementary and Integrative Health (NCCIH)US National Institutes of Health
- Study start
- 8 Nov 2026 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 24 Apr 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.
This pilot study will test an innovative way to establish how pain medicines provide analgesia in healthy adults. The study uses a group of short, controlled pain tests to look at different types of pain responses in the body. The main goal is to find out if this testing approach can show the pain-relieving effects of 2 medicines, pregabalin and naproxen versus placebo, and show how they provide relief of different types of pain.
The study hypothesis is that this pain testing approach administered as a battery would be able to tell the difference between a medicine that works mainly in the brain and spinal cord (pregabalin) and a medicine that works mainly on inflammation in body tissues (naproxen).
Up to 25 healthy adults will take part. Each participant will receive all 3 study treatments, pregabalin, naproxen, and placebo, administered in random order during separate study periods. The order will be assigned by chance. Neither the participant nor the study team will know which treatment is given at each visit.
The study includes several experimental pain tests. These include:
a heat and capsaicin skin test that causes short-term skin sensitivity,
a UVB light test that causes a temporary sunburn-like sensitivity, and
a cold pressor test, in which a hand is placed in very cold water for a short time.
Participants will also have sensory testing to measure how they feel touch, pressure, pinprick, warmth, heat, and cold. Blood samples will be collected to measure study drug levels. Urine samples, vital signs, and other safety checks will also be done.
Each treatment visit includes testing before and for several hours after taking the study drug. There will be a washout period of at least 48 hours between treatments. Total participation may last up to about 10 weeks.
This study is not expected to provide direct medical benefit to participants. The information learned may help researchers improve early testing of future pain treatments....
Detailed description
Study Description:
This pilot study is designed to validate the performance characteristics of HEMP. This pilot study is a single-center, randomized, double-blind, three-period, three-treatment crossover designed to investigate how well the HEMP model distinguishes the analgesic properties of two medications, one which acts centrally and the other one acts peripherally.
Up to 25 healthy adults will be enrolled in this study, which will consist of a screening phase and a treatment phase with three periods. Participants will be randomly assigned to receive either a gabapentinoid (pregabalin), a non-steroidal anti-inflammatory drug (NSAID) (naproxen), or a placebo during each period of the treatment phase (see Table 2 for the study drugs). Each dose will be separated by a wash-out period of at least 48 hours.
Assessments will be performed at baseline and over a period of 8 hours following each drug administration to establish pharmacodynamic, pharmacokinetic, and safety properties of the treatments.
Objectives:
Primary Objective:
To establish the ability of HEMP to demonstrate the analgesic efficacy of pregabalin and naproxen based on their known mechanisms of action (central vs. peripheral, respectively) as measured by the severity of experimental pain, allodynia, and hyperalgesia across three pain models.
Secondary Objectives:
To demonstrate that HEMP can determine factors that differentiate responders from non-responders to the study drugs, when evaluating their analgesic properties of these drugs in humans.
Endpoints:
Pharmacodynamics (PD) Primary Endpoint:
- Change from baseline in pain intensity (PI) visual analog scale (VAS) score for allodynia (soft brush) after first heat/capsaicin application (HCM)
- Change from baseline in PI VAS score for hyperalgesia (pin-prick) after first HCM
- Change from baseline in PI VAS score for hyperalgesia (pin-prick) ultraviolet (UVB) light exposure.
- Change from baseline in PI VAS score for heat hyperalgesia (thermal-heat pain) UVB
- Change from baseline in PI VAS score after hand removal in Cold Pressor Test (CPT), i.e., cold water immersion
Secondary Endpoints:
- Weighted mean (based on area under the curve (AUC)) VAS score for spontaneous pain over 0-60 mins following first and second HCM.
- Area of secondary hyperalgesia to pin-pick after HCM following first and second HCM
- Change from baseline in PI VAS score for thermal-heat hyperalgesia following first and second HCM
- Proportion of participant who had at least 30% reduction in PI VAS scores from baseline after a Quantitative Sensory Testing (QST) measure (soft brush, light pressure, pin-prick, thermal contact- warm, thermal contact-heat pain, cold) after first and second HCM and UVB PK parameters (e.g., AUClast, Clast, Cmax, tmax)
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Sequence ABC (Pregabalin - Naproxen - Placebo) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive single-dose oral pregabalin 300 mg in Period 1, naproxen 550 mg in Period 2, and matching placebo in Period 3. Treatment periods are separated by at least 48 hours. |
| Sequence ACB (Pregabalin - Placebo - Naproxen) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive single-dose oral pregabalin 300 mg in Period 1, matching placebo in Period 2, and naproxen 550 mg in Period 3. Treatment periods are separated by at least 48 hours. |
| Sequence BAC (Naproxen - Pregabalin - Placebo) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive single-dose oral naproxen 550 mg in Period 1, pregabalin 300 mg in Period 2, and matching placebo in Period 3. Treatment periods are separated by at least 48 hours. |
| Sequence BCA (Naproxen - Placebo - Pregabalin) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive single-dose oral naproxen 550 mg in Period 1, matching placebo in Period 2, and pregabalin 300 mg in Period 3. Treatment periods are separated by at least 48 hours. |
| Sequence CAB (Placebo - Pregabalin - Naproxen) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive matching placebo in Period 1, pregabalin 300 mg in Period 2, and naproxen 550 mg in Period 3. Treatment periods are separated by at least 48 hours. |
| Sequence CBA (Placebo - Naproxen - Pregabalin) | Experimental | Drug: Placebo, Drug: Naproxen, Drug: PregabalinParticipants assigned to this sequence will receive matching placebo in Period 1, naproxen 550 mg in Period 2, and pregabalin 300 mg in Period 3. Treatment periods are separated by at least 48 hours. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- For an individual to be eligible to participate in this study, they must meet all of the following criteria:
- Voluntarily consent to participate and provide written informed consent prior to the start of any study-specific procedures.
- Read and speak English fluently.
- State willingness to comply with all study procedures and availability for the duration of the study.
- Are not pregnant or breastfeeding.
Key exclusion criteria (17 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Have a history or presence of clinically significant cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine, immunologic, dermatologic, neurologic, oncologic, or psychiatric disease or any other condition that, in the opinion of the Investigator, would jeopardize the safety of the participant or the validity of the study results.
- Have alcohol or drug dependence (excluding nicotine and caffeine) within the past 2 years, as defined by the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM IV-TR) and/or participants who have ever been in a substance or alcohol rehabilitation program to treat their substance dependence are currently seeking such treatment.
- Have a clinically significant abnormal finding on the physical exam, medical history, or clinical laboratory results at screening.
- Have a history of psychotic reactions, a non-psychotic emotional disorder, or another mental illness that, in the opinion of the investigator, may affect the ability of the participant to participate in the study.
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 |
|---|---|---|
| PlaceboOver-encapsulated matching placebo administered as a single oral dose in one treatment period of this randomized, double-blind, 3-period crossover study. The placebo is made to look identical to active study drug capsules to maintain blinding. Each participant receives placebo once, with at least 48 hours washout between treatment periods. | Drug | Sequence ABC (Pregabalin - Naproxen - Placebo), Sequence ACB (Pregabalin - Placebo - Naproxen), Sequence BAC (Naproxen - Pregabalin - Placebo), Sequence BCA (Naproxen - Placebo - Pregabalin), Sequence CAB (Placebo - Pregabalin - Naproxen), Sequence CBA (Placebo - Naproxen - Pregabalin) |
| NaproxenOver-encapsulated oral naproxen, 550 mg, administered as a single dose in one treatment period of this randomized, double-blind, 3-period crossover study. Each participant receives naproxen once, with at least 48 hours washout between treatment periods. | Drug | Sequence ABC (Pregabalin - Naproxen - Placebo), Sequence ACB (Pregabalin - Placebo - Naproxen), Sequence BAC (Naproxen - Pregabalin - Placebo), Sequence BCA (Naproxen - Placebo - Pregabalin), Sequence CAB (Placebo - Pregabalin - Naproxen), Sequence CBA (Placebo - Naproxen - Pregabalin) |
| PregabalinOver-encapsulated oral pregabalin, 300 mg, administered as a single dose in one treatment period of this randomized, double-blind, 3-period crossover study. Each participant receives pregabalin once, with at least 48 hours washout between treatment periods. | Drug | Sequence ABC (Pregabalin - Naproxen - Placebo), Sequence ACB (Pregabalin - Placebo - Naproxen), Sequence BAC (Naproxen - Pregabalin - Placebo), Sequence BCA (Naproxen - Placebo - Pregabalin), Sequence CAB (Placebo - Pregabalin - Naproxen), Sequence CBA (Placebo - Naproxen - Pregabalin) |
Primary outcome
Change from baseline in pain intensity after cold pressor test
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in participant-rated pain intensity VAS score measured immediately after hand removal from cold water during the cold pressor test (CPT). Higher scores indicate greater pain intensity.
Change from baseline in pain intensity for allodynia (soft brush) after first heat/capsaicin pain model application
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in participant-rated pain intensity VAS score for soft-brush allodynia at the heat/capsaicin pain model (HCM) site after the first HCM application. Higher scores indicate greater pain intensity.
Change from baseline in pain intensity for hyperalgesia (pin-prick) after first heat/capsaicin pain model application
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in participant-rated pain intensity VAS score for pin-prick hyperalgesia at the HCM site after the first HCM application. Higher scores indicate greater pain intensity.
Change from baseline in pain intensity for mechanical hyperalgesia (pin-prick) at the UVB site
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in participant-rated pain intensity VAS score for pin-prick hyperalgesia at the UVB-treated skin site. Higher scores indicate greater pain intensity.
Change from baseline in pain intensity for thermal hyperalgesia (heat pain) at the UVB site
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Change from baseline in participant-rated pain intensity VAS score for thermal-heat pain hyperalgesia at the UVB-treated skin site. Higher scores indicate greater pain intensity.
5 secondary outcomes
Weighted mean pain intensity VAS score for spontaneous pain over 0 to 60 minutes following first and second HCM applications
Time frame: 0 to 60 minutes after the first and second HCM applications during each treatment period
Area of secondary hyperalgesia to pin-prick following first and second HCM applications
Time frame: After the first and second HCM applications during each treatment period
Change from baseline in pain intensity VAS score for thermal-heat hyperalgesia following first and second HCM applications
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Proportion of participants with at least 30% reduction from baseline in pain intensity VAS score after QST measures at HCM and UVB sites
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
Pharmacokinetic parameters of pregabalin and naproxen
Time frame: Predose and 30, 90, 180, 240, 360, and 420 minutes after dosing in each active treatment period
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual participant data underlying the results reported for this study may be shared upon request after completion of the primary endpoints. This may include baseline demographic and eligibility data, treatment sequence/assignment, pharmacodynamic data from the HEMP procedures and quantitative sensory testing (including VAS pain ratings from HCM, UVB, and cold pressor testing), pharmacokinetic concentration data and derived PK parameters, and safety data such as adverse events, vital signs, and clinical laboratory results. Data sharing will be handled by the PI or designee in accordance with NIH policies and applicable IRB/privacy requirements.
Related trials for Acute Pain
Not yet recruitingPhase 2
Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers
Healthy Volunteers
Not yet recruiting
Battlefield Acupressure for Acute Back Pain Management in the Emergency Department
Acute Back Pain
Recruiting
Ultrasound-Guided Serratus Posterior Superior Intercostal Plane Block for Analgesia in Arthroscopic Shoulder Surgery
Postoperative Pain, Acute, Shoulder Pain
RecruitingPhase 4
Assessment of the Value of FAPI and FDG-PET-CT in Diagnosis of Acute Phase Peyronie's Disease
Peyronie's Disease
RecruitingObservational study
Stroke Hemiplegic Shoulder Pain: Ultrasound Findings and VAS (Cross-Sectional)
Hemiplegic Shoulder Pain, Stroke
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.
Miroslav Backonja, M.D. principal investigator
National Center for Complementary and Integrative Health (NCCIH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Naproxen and Pregabalin in people with Acute Pain, run by National Center for Complementary and Integrative Health (NCCIH) at 1 site in United States.
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 12 inclusion and 17 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: opening soon, as of the sponsor's last update on 3 Nov 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 United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Miroslav Backonja, M.D. ((301) 402-5679, misha.backonja@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in pain intensity after cold pressor test (time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 3 Nov 2026.