Back to resultsChasing Biomarkers in Post-concussion Syndrome
Primary Purpose
Post Concussive Symptoms
Status
Completed
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Early intervention programme
Enhanced usual care
Sponsored by
About this trial
This is an interventional basic science trial for Post Concussive Symptoms
Eligibility Criteria
Patients with severe post-concussive symptoms: Inclusion Criteria: Concussion caused by a head trauma based on the diagnostic criteria recommended by the World Health Organization (WHO) Task Force Age between 18 and 30 years Able to understand, speak and read Danish. A score of 20 or more on the Rivermead Post Concussion Symptoms Questionnaire (RPQ). Exclusion Criteria: Objective neurological findings indicating neurological disease or brain damage. Previous concussion leading to persistent post-concussional symptoms within the last two years. Severe misuse of alcohol, prescription drugs and / or illegal drugs. Severe psychiatric, neurological,or other medical disease that would impede participation in the intervention Inability to speak and read Danish Healthy control group (recruited from December 2021 - March 2022): - Individuals from the Blood Bank at Aarhus University Hospital in Denmark. Inclusion criteria were: Age between 18-30 years Equal distribution between the genders (60 men and 60 women). This number was based on a power analysis using published data from neurofilament light chain.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Enhanced Usual Care
Enhanced Usual Care + Early intervention programme
Arm Description
For more details on the intervention, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145). Enhanced Usual Care (EUC) All patients had a brief clinical psychiatric and neurological assessment in order to determine eligibility, and they were provided with information and advice about typical post-concussional symptoms, the typical recovery process and the use of pain medication.
For more details on the intervention, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145). Behavioral: EUC + Early intervention programme All patients had a brief clinical psychiatric and neurological assessment in order to determine eligibility, and were provided with information and advice about typical post-concussional symptoms, the typical recovery process and the use of pain medication. The early intervention programme was interdisciplinary and was provided by an occupational therapist and a physiotherapist under supervision of a neuropsychologist. It was based on psychoeducation and principles from Cognitive Behavioral Therapy and Graded Exercise Therapy and targeted to patients' individual goals. Patients received 8 weekly treatment sessions (3 group based and 5 individual sessions). The intervention started approximately 4 months after the concussion.
Outcomes
Primary Outcome Measures
Neurofilament light chain at baseline (primary outcome)
The investigators hypothesized:
The concentration of neurofilament light chain (ng/L) is significantly increased at baseline in patients compared to the healthy control group.
Neurofilament light chain at follow-up (primary outcome)
The investigators hypothesized:
1)The neurofilament light chain concentration (ng/L) normalizes (decreases) at follow-up compared to the baseline concentration in patients.
Self-reported post-concussion symptoms score (primary outcome)
The symptom score was measured at both baseline and follow-up using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) which is a self-reported questionnaire. The Rivermead Post-Concussion Symptoms Questionnaire contains 16 items which is rated from 0 (not experienced) to 4 (a severe problem).
The total score thus ranges on a scale between 0-64.
Calcitonin-gene related peptide at baseline (CGRP)
The investigators hypothesized:
The concentration of calcitonin gene-related peptide (pg/mL) is decreased compared to the healthy control group at baseline
Calcitonin-gene related peptide at follow-up (CGRP)
The investigators hypothesized:
The CGRP concentrations (pg/mL) will normalize (increase) at follow-up compared to baseline.
Secondary Outcome Measures
Quinolinic acid at baseline
The investigators hypothesized that:
The concentration of the neurotoxic metabolite, quinolinic acid (measured in nM), is increased in patients compared to healthy controls
Quinolinic acid at follow-up
The investigators hypothesized:
The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.
Neuroprotective index at baseline
The investigators hypothesized:
The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (KynA/QUIN) is lower than the ratio in healthy individuals at baseline.
A higher ratio means a better outcome.
Neuroprotective index at follow-up
The investigators hypothesized:
The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (QUIN) normalizes (increases) at follow-up compared to baseline. A higher ratio thus means a better outcome.
Inflammatory markers at baseline
The investigators hypothesized that:
Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) (both pg/mL) are increased in patients compared to healthy controls.
Inflammatory markers at baseline
The investigators hypothesized:
Basic fibroblast growth factor (Basic FGF), Eotaxin, interferon gamma (IFN-y), interleukin 1 beta (IL-1B), interleukin 8 (IL-8), interleukin 9 (IL-9), interleukin 17 (IL17), Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and Macrophage Inflammatory Protein beta (MIP-1b) (all pg/mL) are significantly increased in patients compared to controls (hypothesis is based on a recent study (PMID: 32326805)
Inflammatory markers at follow-up
TNF-α and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.
Full Information
NCT ID
NCT05812742
First Posted
March 1, 2023
Last Updated
July 31, 2023
Sponsor
University of Aarhus
Collaborators
Sygekassernes Helsefond, Fonden til Lægevidenskabens Fremme, Direktør Emil C. Hertz og Hustru Inger Hertz Fond, Helga Og Peter Kornings Fond, Region MidtJylland Denmark
1. Study Identification
Unique Protocol Identification Number
NCT05812742
Brief Title
Chasing Biomarkers in Post-concussion Syndrome
Official Title
Neurofilament Light Chain, Inflammatory Markers, Calcitonin Gene-related Peptide, and Kynurenine Metabolites in Patients With Severe Post-concussive Symptoms
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
March 2015 (Actual)
Primary Completion Date
July 2023 (Actual)
Study Completion Date
July 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
Sygekassernes Helsefond, Fonden til Lægevidenskabens Fremme, Direktør Emil C. Hertz og Hustru Inger Hertz Fond, Helga Og Peter Kornings Fond, Region MidtJylland Denmark
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The goal of this study was to investigate the biomarkers, neurofilament light chain, inflammatory markers, calcitonin-gene-related peptide, and metabolites from the kynurenine pathway in patients with severe post-concussive symptoms. The main question it aimed to answer was:
Are the biomarker concentrations significantly changed in patients with severe post-concussive symptoms compared to healthy individuals?
Do the biomarker concentrations change at follow-up?
Participants were recruited from a recently published randomized controlled trial (Clinicaltrials.gov no. NCT02337101 / PMID: 31891145 ). The biomarker concentrations were compared to a healthy control group recruited from the Blood Bank at Aarhus University Hospital in 2022.
Detailed Description
In the previously published RCT-study (PMID: 31891145), 86 participants with severe post-concussive symptoms provided blood samples at baseline (4 months after the concussion). Severe post-concussive symptoms were defined as having a Rivermead Post Concussion Questionnaire >20.
Around 7 months later, a follow-up blood sample was obtained from 54 participants.
These blood samples were used to investigate blood biomarkers for the condition.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Post Concussive Symptoms
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
86 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Enhanced Usual Care
Arm Type
Active Comparator
Arm Description
For more details on the intervention, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Enhanced Usual Care (EUC) All patients had a brief clinical psychiatric and neurological assessment in order to determine eligibility, and they were provided with information and advice about typical post-concussional symptoms, the typical recovery process and the use of pain medication.
Arm Title
Enhanced Usual Care + Early intervention programme
Arm Type
Experimental
Arm Description
For more details on the intervention, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Behavioral: EUC + Early intervention programme All patients had a brief clinical psychiatric and neurological assessment in order to determine eligibility, and were provided with information and advice about typical post-concussional symptoms, the typical recovery process and the use of pain medication.
The early intervention programme was interdisciplinary and was provided by an occupational therapist and a physiotherapist under supervision of a neuropsychologist. It was based on psychoeducation and principles from Cognitive Behavioral Therapy and Graded Exercise Therapy and targeted to patients' individual goals.
Patients received 8 weekly treatment sessions (3 group based and 5 individual sessions). The intervention started approximately 4 months after the concussion.
Intervention Type
Behavioral
Intervention Name(s)
Early intervention programme
Intervention Description
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Intervention Type
Behavioral
Intervention Name(s)
Enhanced usual care
Intervention Description
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Primary Outcome Measure Information:
Title
Neurofilament light chain at baseline (primary outcome)
Description
The investigators hypothesized:
The concentration of neurofilament light chain (ng/L) is significantly increased at baseline in patients compared to the healthy control group.
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Neurofilament light chain at follow-up (primary outcome)
Description
The investigators hypothesized:
1)The neurofilament light chain concentration (ng/L) normalizes (decreases) at follow-up compared to the baseline concentration in patients.
Time Frame
The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Title
Self-reported post-concussion symptoms score (primary outcome)
Description
The symptom score was measured at both baseline and follow-up using the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) which is a self-reported questionnaire. The Rivermead Post-Concussion Symptoms Questionnaire contains 16 items which is rated from 0 (not experienced) to 4 (a severe problem).
The total score thus ranges on a scale between 0-64.
Time Frame
The baseline symptom score (RPQ) was obtained from the patients up to 7 months after the concussion (4 months median), and the follow-up score was obtained up to 16 months (10.5 median) after the concussion
Title
Calcitonin-gene related peptide at baseline (CGRP)
Description
The investigators hypothesized:
The concentration of calcitonin gene-related peptide (pg/mL) is decreased compared to the healthy control group at baseline
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Calcitonin-gene related peptide at follow-up (CGRP)
Description
The investigators hypothesized:
The CGRP concentrations (pg/mL) will normalize (increase) at follow-up compared to baseline.
Time Frame
The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Secondary Outcome Measure Information:
Title
Quinolinic acid at baseline
Description
The investigators hypothesized that:
The concentration of the neurotoxic metabolite, quinolinic acid (measured in nM), is increased in patients compared to healthy controls
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Quinolinic acid at follow-up
Description
The investigators hypothesized:
The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.
Time Frame
The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Title
Neuroprotective index at baseline
Description
The investigators hypothesized:
The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (KynA/QUIN) is lower than the ratio in healthy individuals at baseline.
A higher ratio means a better outcome.
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Neuroprotective index at follow-up
Description
The investigators hypothesized:
The ratio between the neuroprotective metabolite kynurenic acid (KYNA) and the neurotoxic metabolite quinolinic acid (QUIN) normalizes (increases) at follow-up compared to baseline. A higher ratio thus means a better outcome.
Time Frame
The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Title
Inflammatory markers at baseline
Description
The investigators hypothesized that:
Tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) (both pg/mL) are increased in patients compared to healthy controls.
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Inflammatory markers at baseline
Description
The investigators hypothesized:
Basic fibroblast growth factor (Basic FGF), Eotaxin, interferon gamma (IFN-y), interleukin 1 beta (IL-1B), interleukin 8 (IL-8), interleukin 9 (IL-9), interleukin 17 (IL17), Interferon gamma-induced protein 10 (IP-10), monocyte chemoattractant protein 1 (MCP-1), and Macrophage Inflammatory Protein beta (MIP-1b) (all pg/mL) are significantly increased in patients compared to controls (hypothesis is based on a recent study (PMID: 32326805)
Time Frame
The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Title
Inflammatory markers at follow-up
Description
TNF-α and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.
Time Frame
The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Patients with severe post-concussive symptoms:
Inclusion Criteria:
Concussion caused by a head trauma based on the diagnostic criteria recommended by the World Health Organization (WHO) Task Force
Age between 18 and 30 years
Able to understand, speak and read Danish.
A score of 20 or more on the Rivermead Post Concussion Symptoms Questionnaire (RPQ).
Exclusion Criteria:
Objective neurological findings indicating neurological disease or brain damage.
Previous concussion leading to persistent post-concussional symptoms within the last two years.
Severe misuse of alcohol, prescription drugs and / or illegal drugs.
Severe psychiatric, neurological,or other medical disease that would impede participation in the intervention
Inability to speak and read Danish
Healthy control group (recruited from December 2021 - March 2022):
- Individuals from the Blood Bank at Aarhus University Hospital in Denmark.
Inclusion criteria were:
Age between 18-30 years
Equal distribution between the genders (60 men and 60 women). This number was based on a power analysis using published data from neurofilament light chain.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Preben Eggertsen, MD
Organizational Affiliation
Hammel Neurorehabilitation Centre and University Research Clinic and Research Unit for Molecular Medicine (Aarhus University)
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Chasing Biomarkers in Post-concussion Syndrome
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