Test Retest Reliability of OA and OH

Test Retest Reliability of Offset Analgesia and Onset Hyperalgesia Paradigm

The goal of this study is to measure the test retest reliability of offset analgesia (OA) and onset hyperalgesia (OH) across multiple study visits. OA and OH are quantitative sensory tests (QST) thought to measure how the brain modulates pain. This study will use a heat thermode to induce OA and OH in healthy, pain-free volunteers across 3 study visits. Additional QST measures and survey data relevant to pain modulation will be collected. This study lays the foundation required to use OA and OH as tools to measure pain modulation in clinical trials. Following their validation, we anticipate that OA and OH will serve as predictive and therapeutic biomarkers, which will aid both in the development of novel analgesics and in treatment selection leading to the personalization of pain management.

Study Overview

• Status: Completed
• Conditions: Pain; Analgesia; Pain Catastrophizing
• Intervention / Treatment: Behavioral: Medoc cutaneous probe; Behavioral: Quantitative sensory testing; Behavioral: Computer tasks

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15206
      • UPMC Pain Medicine at Centre Commons

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy volunteers with no chronic pain issues who can understand the study procedures

Exclusion Criteria:

• History of chronic pain
• Current significant pain disorder
• Active ongoing pain every day that is acute or chronic in duration
• Recent history of migraine (1 attack in last 24 months)
• Lifetime history mood disorders (anxiety, depression, bipolar) or psychotic disorders.
• Subjects taking psychotropics (e.g. benzodiazepines, antidepressants), or medications known to affect the autonomic nervous system (e.g. beta-receptor agonists or antagonists) will be excluded.
• Cognitive impairment affecting the ability to provide informed consent, understand directions, and participate in study procedures
• Uncontrolled or unstable medical disorder preventing participation in study procedures
• Pregnancy
• Tattoos on forearm
• History of brain surgery
• Nonambulatory status
• Heart problems such as an irregular heart beat or coronary artery disease
• Neurological problems such as seizure, fainting spells, recurrent severe headache, stroke, transient ischemic attack
• High blood pressure
• Severe liver disease
• Severe gastrointestinal disease
• Chronic severe infectious disease (e.g. HIV/AIDS)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Volunteers; QST devices and computer tasks are used to measure OA, OH, pain intensity, and other outcomes	Behavioral: Medoc cutaneous probe; A computer-controlled probe delivers temperatures to the skin to measure pain, OA, and OH; Behavioral: Quantitative sensory testing; Standard methods involving pinprick, pressure, heat, and cold applied to the skin are used to measure sensation and pain; Behavioral: Computer tasks; QST and computer tasks are used to measure changes in pain intensity

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Offset analgesia and onset hyperalgesia	Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at baseline	baseline
Test retest reliability of offset analgesia and onset hyperalgesia	Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at 1 week after baseline	1 week post baseline
Test retest reliability of offset analgesia and onset hyperalgesia	Pain intensity difference during heat stimuli measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable) at 4 weeks after baseline	4 weeks post baseline
Differences in brain region activation- QST (quantitative sensory tests)	Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures.	baseline
Test retest reliability in brain region activation- QST (quantitative sensory tests)	Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures at 1 week after baseline	1 week post baseline
Test retest reliability in brain region activation- QST (quantitative sensory tests)	Difference in brain region activation (as measured by oxygenated hemoglobin, HbO) between central nervous system inhibition and control stimuli during QST procedures at 4 weeks after baseline	4 weeks post baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in resting fNIRS signaling	Differences in fNIRS resting state connectivity as measured by brain region activation	baseline
Questionnaire score- State Trait Anxiety Inventory (STAI) Y1-2	Standardized survey score of state trait anxiety inventory Y1 and Y2 assessing anxiety before QST procedures on visit 1 only. State Anxiety Score ranges from 20-80. Trait Anxiety Score ranges from 20-80. Higher scores indicate worse anxiety state and trait symptoms.	baseline
Questionnaire score- Pain Catastrophizing Scale (PCS)	Standardized survey score assessing pain perception before QST procedures at visit 1 only. Rumination subscale score ranges from 0-16. Magnification subscale score ranges 0-12. Helplessness subscale score ranges from 0-24. Total score can be calculated by summing subscales. Total score ranges from 0-52, with higher scores indicating more pain catastrophizing.	baseline
Questionnaire score- STAI Y1 post testing	Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state.	baseline
Questionnaire score- STAI Y1 post testing	Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state.	1 week after baseline
Questionnaire score- STAI Y1 post testing	Standardized survey score of state trait anxiety inventory Y1 assessing anxiety immediately after QST procedures measured at all 3 visits. Higher scores indicate worse anxiety state.	4 weeks after baseline
Questionnaire score- Situational Pain Catastrophizing Scale post testing	Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing.	baseline
Questionnaire score- Situational Pain Catastrophizing Scale post testing	Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing.	1 week after baseline
Questionnaire score- Situational Pain Catastrophizing Scale post testing	Standardized survey score assessing pain perception immediately after QST procedures are completed at each visit. Scores range from 0-24, with higher scores representing more pain catastrophizing.	4 weeks after baseline
Questionnaire score- Beck Depression Inventory-II (BDI-II)	Standardized survey assessing depression at the start of visit 1. Scores range from 0-63. Total score of 0-13 is considered minimal range of depression, 14-19 is mild, 20-28 is moderate, and 29-63 is severe depression.	baseline
Questionnaire score- Generalized Anxiety Disorder 2-item (GAD-2)	Standardized survey score of GAD-2 assessing anxiety at the start of visit 1. Scores range from 0-6. Higher scores indicate higher likelihood of having GAD.	baseline
Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2	Standardized survey score of MAIA-2 assessing mindfulness at the start of visit 1. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness.	baseline
Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing	Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness.	baseline
Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing	Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness.	1 week after baseline
Questionnaire score- Multidimensional Assessment of Interoceptive Awareness (MAIA) Version 2 post testing	Standardized survey score of MAIA-2 assessing mindfulness after QST measured at all 3 visits. Total scores range from 0-160 with 8 subscales. Higher scores indicate higher levels of mindfulness.	4 weeks after baseline
Pain intensity	Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable)	baseline
Pain intensity	Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable)	1 week after baseline
Pain intensity	Changes in pain intensity during quantitative sensory tests and computer tasks measured on a 0-100 sliding scale (0 is no pain, 100 is the most intense pain imaginable)	4 weeks after baseline

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Investigators: Principal Investigator: Benedict Alter, MD, PhD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): August 5, 2022
• Primary Completion (Actual): April 10, 2024
• Study Completion (Actual): April 10, 2024

Study Registration Dates

• First Submitted: August 2, 2022
• First Submitted That Met QC Criteria: August 2, 2022
• First Posted (Actual): August 4, 2022

Study Record Updates

• Last Update Posted (Actual): June 20, 2024
• Last Update Submitted That Met QC Criteria: June 18, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: STUDY22010185

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data will be available, including data dictionaries, after publication per journal and funding protocols. The statistical analysis plan and analytic code will also be available per the same protocols.
• IPD Sharing Time Frame: Data will become available after publication per journal and funding entity protocols.
• IPD Sharing Access Criteria: Data will be made available by reasonable request and/or per journal and funding entity protocols.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No