Discovery and Analytical Validation of Inflammatory Bio-signatures of the Human Pain Experience

NCT05074485 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: HSC-MS-19-0627R61NS113316
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The first objective of the study is to evaluate whether a novel bio-signature (derived from a wide range of pro- and anti-nociceptive IL-1 family cytokine activity) will predict pain experienced and also release of underlying endogenous opioid neurotransmitters during an experimental nociceptive pain challenge, which will be performed while simultaneously quantifying mu-opioid receptor activity in the brain via \[11C\]-carfentanil PET neuroimaging in healthy subjects. Another objective is to evaluate whether an anti-inflammatory drug that reduces activation of IL-1b (minocycline) will perturb the balance between pro- and anti-nociceptive IL-1 cytokines and effect a reduction in pain experienced (and endogenous opioids released) during the experimental, nociceptive pain challenge. A final objective is to evaluate performance characteristics (sensitivity, accuracy, dynamic range) of the biosignature for the purpose of predicting post-operative pain.

Conditions

Pain

Outcome Measures

Primary Outcomes (5)

• Pain as assessed by total pain score on the McGill Pain Questionnaire

  The total pain score on the McGill Pain Questionnaire ranges from 0-78, with a higher score indicating greater pain.

  0 minutes, This represents the study baseline, prior to any brain imaging

• Pain as assessed by total pain score on the McGill Pain Questionnaire

  The total pain score on the McGill Pain Questionnaire ranges from 0-78, with a higher score indicating greater pain.

  90 minutes, upon completion of brain imaging

• Pain as assessed by total pain score on the McGill Pain Questionnaire

  The total pain score on the McGill Pain Questionnaire ranges from 0-78, with a higher score indicating greater pain.

  12 to 24 hours before elective surgery

• Pain as assessed by total pain score on the McGill Pain Questionnaire

  The total pain score on the McGill Pain Questionnaire ranges from 0-78, with a higher score indicating greater pain.

  24 to 48 hours after elective surgery

• Pain as assessed by total pain score on the McGill Pain Questionnaire

  The total pain score on the McGill Pain Questionnaire ranges from 0-78, with a higher score indicating greater pain.

  6 to 8 weeks after elective surgery

Study Arms (2)

Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challenge

EXPERIMENTAL

Pharmacological challenge (with placebo) plus nociceptive pain challenge, then pharmacological challenge (with anakinra) plus nociceptive pain challenge

Drug: anakinra; Drug: Placebo; Other: Nociceptive pain challenge

Anakinra plus nociceptive pain challenge, then placebo plus nociceptive pain challenge

EXPERIMENTAL

Pharmacological challenge (with anakinra) plus nociceptive pain challenge, then pharmacological challenge (with placebo) plus nociceptive pain challenge

Drug: anakinra; Drug: Placebo; Other: Nociceptive pain challenge

Interventions

anakinra DRUG

intravenous injection of 100 milligrams anakinra

Also known as: Kineret

Anakinra plus nociceptive pain challenge, then placebo plus nociceptive pain challenge; Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challenge

Placebo DRUG

intravenous injection of 1 milliliter normal saline

Also known as: Inert Substance

Anakinra plus nociceptive pain challenge, then placebo plus nociceptive pain challenge; Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challenge

Nociceptive pain challenge OTHER

The experimental, standardized, nociceptive pain challenge will induce a moderate level of sustained pain. The pain challenge involves a masseteric injection in the left or right jaw muscle of normal saline (0.15 ml bolus of 0.9% normal saline) over a 15 second period followed by continuous infusion via a closed loop infusion system for 20 minutes.

Also known as: Pain Induction

Anakinra plus nociceptive pain challenge, then placebo plus nociceptive pain challenge; Placebo plus nociceptive pain challenge, then anakinra plus nociceptive pain challenge

Eligibility Criteria

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

You may qualify if:

• Obese or non-obese
• Awaiting elective surgery
• Negative urine pregnancy test

You may not qualify if:

• Active, severe medical or psychiatric illness (per DSM-V)
• History of depressive and/or anxiety symptoms with or without presence of a DSM-V depressive and/or anxiety disorder
• Current or recent (within past 3 months) suicidal thoughts/plans/attempts
• Current or recent (within past 3 months) substance use/abuse/dependence (Note: stable nicotine use is acceptable, non-risky alcohol use is acceptable)
• Active or chronic medical illness (except obesity: either obese or non-obese volunteers can enroll in the study).
• Recent (past year) PET scan(s).
• Current medication treatment that would impact measures of interest.
• Current pregnancy or recent (within the past 2 months) intercourse without an acceptable contraceptive method

Sponsors & Collaborators

• Alan Prossin: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Pain

Interventions

Interleukin 1 Receptor Antagonist Protein

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Alan R Prossin, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alan R Prossin, MD

CONTACT

(713) 486-2836; Alan.Prossin@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: September 27, 2021
• First Posted: October 12, 2021
• Study Start: July 19, 2021
• Primary Completion: May 7, 2026
• Study Completion: May 7, 2026
• Last Updated: December 5, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)