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 2026-09-25.
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:
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:
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.
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National Center for Complementary and Integrative Health (NCCIH)