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Completed

NCT Number: NCT05812742

Chasing Biomarkers in Post-concussion Syndrome

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.

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Key information

Conditions

Post Concussive Symptoms Brain Concussion Craniocerebral Trauma Head Injuries, Closed Nervous System Diseases Post-Concussion Syndrome Trauma, Nervous System Wounds and Injuries Wounds, Nonpenetrating

Age range

18 year–30 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Early intervention programme

Behavioral

For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).

Enhanced Usual Care

Behavioral

For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).

Primary outcomes

  1. Neurofilament light chain at baseline (primary outcome)

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    The investigators hypothesized:

    The concentration of neurofilament light chain (ng/L) is significantly increased at baseline in patients compared to the healthy control group.

  2. Neurofilament light chain at follow-up (primary outcome)

    Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.

    The investigators hypothesized:

    1)The neurofilament light chain concentration (ng/L) normalizes (decreases) at follow-up compared to the baseline concentration in patients.

  3. Self-reported post-concussion symptoms score (primary outcome)

    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

    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.

  4. Calcitonin-gene related peptide at baseline (CGRP)

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    The investigators hypothesized:

    The concentration of calcitonin gene-related peptide (pg/mL) is decreased compared to the healthy control group at baseline

  5. Calcitonin-gene related peptide at follow-up (CGRP)

    Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.

    The investigators hypothesized:

    The CGRP concentrations (pg/mL) will normalize (increase) at follow-up compared to baseline.

Secondary outcomes

  1. Quinolinic acid at baseline

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    The investigators hypothesized that:

    The concentration of the neurotoxic metabolite, quinolinic acid (measured in nM), is increased in patients compared to healthy controls

  2. Quinolinic acid at follow-up

    Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.

    The investigators hypothesized:

    The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.

  3. Neuroprotective index at baseline

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    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.

  4. Neuroprotective index at follow-up

    Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.

    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.

  5. Inflammatory markers at baseline

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    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.

  6. Inflammatory markers at baseline

    Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).

    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)

  7. Inflammatory markers at follow-up

    Time frame: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.

    TNF-α and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.

Sponsors and collaborators

Lead sponsor

University of Aarhus

Other

Collaborators

  • Direktør Emil C. Hertz og Hustru Inger Hertz Fond
  • Fonden til Lægevidenskabens Fremme
  • Helga Og Peter Kornings Fond
  • Region MidtJylland Denmark
  • Sygekassernes Helsefond

Registry information

Official study title

Neurofilament Light Chain, Inflammatory Markers, Calcitonin Gene-related Peptide, and Kynurenine Metabolites in Patients With Severe Post-concussive Symptoms

Important dates

Study start
2015
Primary completion
2023
Study completion
2023
First posted
Apr 14, 2023
Registry last updated
Apr 16, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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