Investigating Composite Biomarkers for Pain Catastrophizing

Pain, Acute Clinical Trial

Official title:

Investigating Composite Biomarkers for Pain Catastrophizing

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04787198
• Other study ID #: N-20200095
• Status: Recruiting
• Phase: N/A
• Start date: October 15, 2022
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: Aalborg University
• Contact: Laura Petrini, PhD
• Phone: 0045 99409826
• Email: lap[@]hst.aau.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 44
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Pain
• Pain, Acute

Intervention

Drug:
• hypertonic saline
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 .
• isotonic saline
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.

Locations

Country	Name	City	State
Denmark	Aalborg University	Aalborg

Sponsors (1)

Lead Sponsor	Collaborator
Aalborg University

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pain Catastrophizing Scale (PCS) questionnaire	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 0 (baseline)
Other	Positive and Negative Affect Schedule (PANAS) questionnaire	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 0 (baseline)
Other	Reinforcement Sensitivity Theory - Personality Questionnaire (RST-PQ).	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 0 (baseline)
Other	State-Trait Anxiety Inventory - Form Y (STAI-Y)	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 0 (baseline)
Other	Heart rate assessment	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 0 (baseline)
Primary	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.	10 minutes of recording before isotonic/hypertonic injection
Primary	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.	10 minutes of recording after isotonic/hypertonic injection
Primary	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.	10 minutes of recording before isotonic/hypertonic injection
Primary	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.	10 minutes of recording after isotonic/hypertonic injection
Primary	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.	time 0 (baseline)
Primary	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.	Time 1 (3 hours)
Primary	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.	time 2 (24 hours)
Primary	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.	time 3 (48 hours)
Primary	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.	time 4 (72 hours)
Primary	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.	time 0 (baseline)
Primary	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.	time 1 (3 hours)
Primary	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.	time 2 (24 hours)
Primary	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.	time 3 (48 hours)
Primary	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.	time 4 (72 hours)
Primary	Proteome analysis	From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.	time 0 (baseline)
Primary	Proteome analysis	From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.	time 1(3 hours)
Primary	Proteome analysis	From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.	time 2 (24 hours)
Primary	Proteome analysis	From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.	time 3 (48 hours)
Primary	Proteome analysis	From the blood samples previously collected, the protein concentration will be determined. Protein sequencing will be done using mass spectrometers.	time 4 (72 hours)
Primary	Metabolome analysis	From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.	time 0 (baseline)
Primary	Metabolome analysis	From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.	time 1(3 hours)
Primary	Metabolome analysis	From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.	time 2 (24 hours)
Primary	Metabolome analysis	From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.	time 3 (48 hours)
Primary	Metabolome analysis	From the blood samples previously collected. Metabolites will be investigated and identified by a 4D feature finding using Metaboscape.	time 4 (72 hours)
Primary	Plasma cortisol levels measurement	From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).	time 0 (baseline)
Primary	Plasma cortisol levels measurements	From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).	time 1(3 hours)
Primary	Plasma cortisol levels measurements	From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).	time 2 (24 hours)
Primary	Plasma cortisol levels measurements	From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).	time 3 (48 hours)
Primary	Plasma cortisol levels measurements	From the blood samples previously collected, plasma levels of cortisol will be evaluated through enzyme-linked immunosorbent assay (ELISA).	time 4 (72 hours)
Primary	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).	time 0 (baseline)
Primary	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).	time 1(3 hours)
Primary	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).	time 2 (24 hours)
Primary	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).	time 3 (48 hours)
Primary	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).	time 4 (72 hours)
Secondary	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.	20 minutes