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Investigating Composite Biomarkers for Pain Catastrophizing

Primary Purpose

Pain, Acute

Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
hypertonic saline
isotonic saline
Sponsored by
Aalborg University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Pain, Acute

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Healthy men and women in the age 18-80 years
  • Speak and understand English

Exclusion Criteria:

  • Acute and chronic pain
  • Pregnancy or breastfeeding
  • Drug addiction defined as the use of cannabis, opioids or other drugs
  • Present or previous history of neurological, dermatological, immunological, musculoskeletal, cardiac disorder or mental illnesses that may affect the results (e.g. Neuropathy, muscular pain in the upper extremities, etc.)
  • Focal and generalized seizure
  • Surgery or any other therapy for epilepsy
  • Present or previous AEDs (anti-epileptic drugs) administration
  • Present or previous use of epileptic devices (<1 year prior the enrolment)
  • Lack of ability to cooperate
  • Current use of medications that may affect the trial, such as antipsychotics and pain killers as well as systemic or topical steroids and anti-inflammatory drugs.
  • Skin diseases
  • Consumption of alcohol or painkillers 24 hours before the study days and between these
  • Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)

Sites / Locations

  • Aalborg UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

hypertonic saline

isotonic saline

Arm Description

Outcomes

Primary Outcome Measures

Oscillations of the main electroencephalogram (EEG) frequency
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Oscillations of the main EEG frequency bands (delta, alpha, beta, gamma) from the frontal and parietal lobes will be detected and correlated to the individual pain rate as well as the dimensions of the psychological questionnaires.
Oscillations of the main electroencephalogram (EEG) frequency
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Oscillations of the main EEG frequency bands (delta, alpha, beta, gamma) from the frontal and parietal lobes will be detected and correlated to the individual pain rate as well as the dimensions of the psychological questionnaires.
Perturbation of the electroencephalogram (EEG) rhythms
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Perturbation of the above-mentioned EEG rhythms will be measured in response to the hypertonic/isotonic saline injection and compared to a resting state baseline recording.
Perturbation of the electroencephalogram (EEG) rhythms
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Perturbation of the above-mentioned EEG rhythms will be measured in response to the hypertonic/isotonic saline injection and compared to a resting state baseline recording.
Collection of blood samples
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Collection of blood samples
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Collection of blood samples
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Collection of blood samples
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Collection of blood samples
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
MicroRNAs (miRNAs) expression analysis
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
MicroRNAs (miRNAs) expression analysis
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
MicroRNAs (miRNAs) expression analysis
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
MicroRNAs (miRNAs) expression analysis
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
MicroRNAs (miRNAs) expression analysis
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Proteome analysis
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Proteome analysis
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Proteome analysis
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Proteome analysis
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Proteome analysis
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Metabolome analysis
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Metabolome analysis
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Metabolome analysis
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Metabolome analysis
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Metabolome analysis
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Plasma cortisol levels measurement
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma cortisol levels measurements
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma cortisol levels measurements
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma cortisol levels measurements
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma cortisol levels measurements
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma Interleukin-6 (IL-6) levels measurements
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma Interleukin-6 levels measurements
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma Interleukin-6 levels measurements
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma Interleukin-6 levels measurements
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Plasma Interleukin-6 levels measurements
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).

Secondary Outcome Measures

Measuring Pain using VAS
The subject will rate the pain intensity continuously for 20 minutes and VAS will start from zero (0), representing no pain, and will end at one hundred (100) representing worst pain imaginable.

Full Information

First Posted
February 16, 2021
Last Updated
October 12, 2022
Sponsor
Aalborg University
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1. Study Identification

Unique Protocol Identification Number
NCT04787198
Brief Title
Investigating Composite Biomarkers for Pain Catastrophizing
Official Title
Investigating Composite Biomarkers for Pain Catastrophizing
Study Type
Interventional

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 15, 2022 (Anticipated)
Primary Completion Date
December 31, 2022 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Aalborg University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Pain is a complex, multidimensional, and subjective experience; and although, investigators use a single word "pain", to describe our perception, multiple mechanisms contribute to the generation and maintenance of pain. To help diagnosing and improving pain management, there is a need for developing tools. These tools may include measurements of substances, or biomarkers, in the blood; e.g. small molecules called microRNA and proteins. In these experiments, the investigators would like to investigate how the psychological response to stress and pain alters the impulses in the brain and the content of microRNA and proteins in the blood. The future aim is to identify patients in high risk of developing and maintaining chronic pain and to be able to treat chronic pain efficiently.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pain, Acute

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
44 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
hypertonic saline
Arm Type
Experimental
Arm Title
isotonic saline
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
hypertonic saline
Intervention Description
The site of injections will be determined by palpation of the contracted First Dorsal Interosseus (FDI) muscle. The skin will be cleaned with alcohol before injection. A bolus injection of hypertonic saline (7% NaCl) will be administered to the FDI muscle using a 1 mL syringe with a disposable needle (27G), and 30 the volume of the bolus will be 0.2 mL .
Intervention Type
Drug
Intervention Name(s)
isotonic saline
Intervention Description
The site of injections will be determined by palpation of the contracted First Dorsal Interosseus (FDI) muscle. The skin will be cleaned with alcohol before injection. A bolus injection of 0.2 mL isotonic saline (9 mg/mL) will be administered to the FDI muscle as control.
Primary Outcome Measure Information:
Title
Oscillations of the main electroencephalogram (EEG) frequency
Description
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Oscillations of the main EEG frequency bands (delta, alpha, beta, gamma) from the frontal and parietal lobes will be detected and correlated to the individual pain rate as well as the dimensions of the psychological questionnaires.
Time Frame
10 minutes of recording before isotonic/hypertonic injection
Title
Oscillations of the main electroencephalogram (EEG) frequency
Description
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Oscillations of the main EEG frequency bands (delta, alpha, beta, gamma) from the frontal and parietal lobes will be detected and correlated to the individual pain rate as well as the dimensions of the psychological questionnaires.
Time Frame
10 minutes of recording after isotonic/hypertonic injection
Title
Perturbation of the electroencephalogram (EEG) rhythms
Description
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Perturbation of the above-mentioned EEG rhythms will be measured in response to the hypertonic/isotonic saline injection and compared to a resting state baseline recording.
Time Frame
10 minutes of recording before isotonic/hypertonic injection
Title
Perturbation of the electroencephalogram (EEG) rhythms
Description
Electroencephalographic (EEG) recording will be performed placing a 64-electrodes cap over the scalp according to the 10-20 international system. Perturbation of the above-mentioned EEG rhythms will be measured in response to the hypertonic/isotonic saline injection and compared to a resting state baseline recording.
Time Frame
10 minutes of recording after isotonic/hypertonic injection
Title
Collection of blood samples
Description
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Time Frame
time 0 (baseline)
Title
Collection of blood samples
Description
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Time Frame
Time 1 (3 hours)
Title
Collection of blood samples
Description
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Time Frame
time 2 (24 hours)
Title
Collection of blood samples
Description
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Time Frame
time 3 (48 hours)
Title
Collection of blood samples
Description
Whole blood samples (5 mL per each time point, a total of 20 mL per subject) will be collected into SST™ II Advance Serum Separation Tubes containing anticoagulant EDTA.
Time Frame
time 4 (72 hours)
Title
MicroRNAs (miRNAs) expression analysis
Description
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Time Frame
time 0 (baseline)
Title
MicroRNAs (miRNAs) expression analysis
Description
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Time Frame
time 1 (3 hours)
Title
MicroRNAs (miRNAs) expression analysis
Description
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Time Frame
time 2 (24 hours)
Title
MicroRNAs (miRNAs) expression analysis
Description
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Time Frame
time 3 (48 hours)
Title
MicroRNAs (miRNAs) expression analysis
Description
From the blood samples previously collected, miRNA will be isolated for a subsequent miRNA library preparation. Subsequently, extracted miRNA will be reversely transcribed, and cDNA will be used for total miRNAs sequencing.
Time Frame
time 4 (72 hours)
Title
Proteome analysis
Description
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Time Frame
time 0 (baseline)
Title
Proteome analysis
Description
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Time Frame
time 1(3 hours)
Title
Proteome analysis
Description
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Time Frame
time 2 (24 hours)
Title
Proteome analysis
Description
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Time Frame
time 3 (48 hours)
Title
Proteome analysis
Description
From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.
Time Frame
time 4 (72 hours)
Title
Metabolome analysis
Description
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Time Frame
time 0 (baseline)
Title
Metabolome analysis
Description
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Time Frame
time 1(3 hours)
Title
Metabolome analysis
Description
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Time Frame
time 2 (24 hours)
Title
Metabolome analysis
Description
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Time Frame
time 3 (48 hours)
Title
Metabolome analysis
Description
From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.
Time Frame
time 4 (72 hours)
Title
Plasma cortisol levels measurement
Description
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 0 (baseline)
Title
Plasma cortisol levels measurements
Description
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 1(3 hours)
Title
Plasma cortisol levels measurements
Description
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 2 (24 hours)
Title
Plasma cortisol levels measurements
Description
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 3 (48 hours)
Title
Plasma cortisol levels measurements
Description
From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 4 (72 hours)
Title
Plasma Interleukin-6 (IL-6) levels measurements
Description
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 0 (baseline)
Title
Plasma Interleukin-6 levels measurements
Description
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 1(3 hours)
Title
Plasma Interleukin-6 levels measurements
Description
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 2 (24 hours)
Title
Plasma Interleukin-6 levels measurements
Description
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 3 (48 hours)
Title
Plasma Interleukin-6 levels measurements
Description
From the blood samples previously collected, plasma levels of IL-6 will be evaluated through enzyme-linked immunosorbent assay (ELISA).
Time Frame
time 4 (72 hours)
Secondary Outcome Measure Information:
Title
Measuring Pain using VAS
Description
The subject will rate the pain intensity continuously for 20 minutes and VAS will start from zero (0), representing no pain, and will end at one hundred (100) representing worst pain imaginable.
Time Frame
20 minutes
Other Pre-specified Outcome Measures:
Title
Pain Catastrophizing Scale (PCS) questionnaire
Description
The PCS assesses negative and exaggerated coping concerning anticipated or experienced painful stimuli. Thirteen items have to be answered on a 5-points Likert-type scale from 0 (non at all) to 4 (all the time).
Time Frame
time 0 (baseline)
Title
Positive and Negative Affect Schedule (PANAS) questionnaire
Description
The PANAS measures positive affects (PA) dimensions ( "the extent to which a person feels active, enthusiastic, and alert") and negative affects (NA) dimensions (a condition of "general distress and unpleasable engagement"). Twenty words are associated with the subject's current feelings and have to be rated on a 5-points Likert-type scale from 1 (non at all) to 5 (extremely).
Time Frame
time 0 (baseline)
Title
Reinforcement Sensitivity Theory - Personality Questionnaire (RST-PQ).
Description
The RST-PQ contains the following subscales: Fight-Flight-Freeze System (FFFS, 10 items), related to active avoidance of adverse stimuli; Behavioral Inhibition System (BIS, 23 items), related to anxiety and passive avoidance of adverse stimuli; Behavioral Approach System (BAS, 32 items), it reflects reward interest, reward reactivity, impulsivity. In total, 65 items have to be answered on a 4-points Likert-type scale, from 1 (non at all) to 4 (highly).
Time Frame
time 0 (baseline)
Title
State-Trait Anxiety Inventory - Form Y (STAI-Y)
Description
The STAI-Y questionnaire measures two types of anxiety, the state and the trait anxiety, as well as the severity of the overall anxiety level. The questionnaire is divided into two sections of 20 items each to be rated on a 4-points Likert-type scale from 1 (non at all) to 4 (very much).
Time Frame
time 0 (baseline)
Title
Heart rate assessment
Description
An electrocardiogram (ECG) will be recorded with a standard 3-lead montage (one electrode on each wrist and the third on the left ankle)
Time Frame
time 0 (baseline)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Healthy men and women in the age 18-80 years Speak and understand English Exclusion Criteria: Acute and chronic pain Pregnancy or breastfeeding Drug addiction defined as the use of cannabis, opioids or other drugs Present or previous history of neurological, dermatological, immunological, musculoskeletal, cardiac disorder or mental illnesses that may affect the results (e.g. Neuropathy, muscular pain in the upper extremities, etc.) Focal and generalized seizure Surgery or any other therapy for epilepsy Present or previous AEDs (anti-epileptic drugs) administration Present or previous use of epileptic devices (<1 year prior the enrolment) Lack of ability to cooperate Current use of medications that may affect the trial, such as antipsychotics and pain killers as well as systemic or topical steroids and anti-inflammatory drugs. Skin diseases Consumption of alcohol or painkillers 24 hours before the study days and between these Participation in other trials within 1 week of study entry (4 weeks in the case of pharmaceutical trials)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laura Petrini, PhD
Phone
0045 99409826
Email
lap@hst.aau.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Petrini, PhD
Organizational Affiliation
Aalborg University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Aalborg University
City
Aalborg
ZIP/Postal Code
9220
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Silvia Lo Vecchio
Phone
+4521397785
Email
slv@hst.aau.dk

12. IPD Sharing Statement

Plan to Share IPD
No

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Investigating Composite Biomarkers for Pain Catastrophizing

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