An interventional study of Placebo and Naproxen in Acute Pain, sponsored by National Center for Complementary and Integrative Health (NCCIH). Not yet recruiting at 1 site in United States. Open to participants aged 18 Years to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by National Center for Complementary and Integrative Health (NCCIH) · Not applicable, Interventional, and Basic science
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....
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:
Secondary Endpoints:
1,073 studies on the registry are indexed under Acute Pain; 166 are open to participants now.
This study's planned enrollment of 25 is below the median of 86 across 902 interventional studies indexed under Acute Pain.
Browse Acute Pain studies →National Center for Complementary and Integrative Health (NCCIH) is the lead sponsor of 223 studies on the registry; 7 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For an individual to be eligible to participate in this study, they must meet all of the following criteria:
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
Drug: Placebo · Drug: Naproxen · Drug: Pregabalin
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.
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.
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period
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.
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
Size of the mapped area of secondary pin-prick hyperalgesia at the HCM site after each HCM application. Larger area indicates greater secondary hyperalgesia.
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
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.
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
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.
Time frame: 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.
Time frame: Predose and 30, 90, 180, 240, 360, and 420 minutes after dosing in each active treatment period
Plan to share: 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.
Time frame: Individual participant data may be available after completion of the primary endpoints. Requests may be made to the PI or designee after primary endpoint completion and will be considered in accordance with NIH policy, IRB approval, and applicable privacy/confidentiality requirements.
Access criteria: De-identified individual participant data may be shared with qualified researchers after completion of the primary endpoints by request to the PI or designee. Requests should describe the proposed research question and analysis plan. Access will be considered in accordance with NIH policies, IRB requirements, and applicable privacy and confidentiality protections. Data will be shared only in a form that protects participant identity, by a mechanism determined by the NIH study team at the time of approval.
Start is estimated for Nov 2026; primary completion for Dec 2029, 37 months later.
Of 424 non-industry interventional studies with no phase under Acute Pain, half reached primary completion within 12 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 23. This study's planned 37 months is above that.
Counting every sponsor, half of 430 studies reached it within 11 months; a quarter within 5 and three quarters within 23.
Start moved 32 times since we started tracking on Sep 25, 2026: Sep 2026 → Nov 2026, last on Nov 10, 2026.
Earlier changes are on the record history on ClinicalTrials.gov ↗
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Naproxen · Pregabalin
National Center for Complementary and Integrative Health (NCCIH) →