Human Experimental Models of Pain (HEMP)

NCT07549490 | Not Yet Recruiting

• 2 other identifiers: 10002450002450-AT
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. 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....

Conditions

Acute Pain

Keywords

Human Experimental Models of Pain; HCM (Heat/Capsaicin Pain Model); Pain Mechanisms

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  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

  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

  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

  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

  Baseline and approximately 2, 5, and 8 hours after dosing in each treatment period

• Pharmacokinetic parameters of pregabalin and naproxen

  Predose and 30, 90, 180, 240, 360, and 420 minutes after dosing in each active treatment period

Study Arms (6)

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.

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.

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.

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.

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.

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.

Drug: Placebo; Drug: Naproxen; Drug: Pregabalin

Interventions

Placebo DRUG

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.

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)

Naproxen DRUG

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.

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)

Pregabalin DRUG

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.

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)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• National Center for Complementary and Integrative Health (NCCIH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Acute Pain; Cardiomyopathy, Hypertrophic

Interventions

Naproxen; Pregabalin

Condition Hierarchy (Ancestors)

Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Aortic Stenosis, Subvalvular; Aortic Valve Stenosis; Aortic Valve Disease; Heart Valve Diseases

Intervention Hierarchy (Ancestors)

Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; gamma-Aminobutyric Acid; Aminobutyrates; Butyrates; Acids, Acyclic; Carboxylic Acids; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Miroslav Backonja, M.D.

  National Center for Complementary and Integrative Health (NCCIH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Miroslav Backonja, M.D.

CONTACT

(301) 402-5679; misha.backonja@nih.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2026
• First Posted: April 24, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 24, 2026

Record last verified: 2026-04-20

Data Sharing

• IPD Sharing: Will share
• 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.

Locations

US (1)