Chasing Biomarkers in Post-concussion Syndrome

Post Concussive Symptoms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05812742
• Other study ID #: Biomarkers in GAIN 1.0
• Status: Completed
• Phase: N/A
• Start date: March 2015
• Est. completion date: July 2023

Study information

• Verified date: February 2023
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 86
• Est. completion date: July 2023
• Est. primary completion date: July 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

Patients with severe post-concussive symptoms:

Inclusion Criteria:

1. Concussion caused by a head trauma based on the diagnostic criteria recommended by the World Health Organization (WHO) Task Force

2. Age between 18 and 30 years

3. Able to understand, speak and read Danish.

4. A score of 20 or more on the Rivermead Post Concussion Symptoms Questionnaire (RPQ).

Exclusion Criteria:

1. Objective neurological findings indicating neurological disease or brain damage.

2. Previous concussion leading to persistent post-concussional symptoms within the last two years.

3. Severe misuse of alcohol, prescription drugs and / or illegal drugs.

4. Severe psychiatric, neurological,or other medical disease that would impede participation in the intervention

5. 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:

1. Age between 18-30 years

2. 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.

Related Conditions & MeSH terms

• Post Concussive Symptoms
• Post-Concussion Syndrome

Intervention

Behavioral:
• Early intervention programme
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
• Enhanced usual care
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).

Locations

Country	Name	City	State
n/a

Sponsors (6)

Lead Sponsor	Collaborator
University of Aarhus	Direktør Emil C. Hertz og Hustru Inger Hertz Fond, Fonden til Lægevidenskabens Fremme, Helga Og Peter Kornings Fond, Region MidtJylland Denmark, Sygekassernes Helsefond

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Primary	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.	The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Primary	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.	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
Primary	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	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Primary	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.	The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Secondary	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	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Secondary	Quinolinic acid at follow-up	The investigators hypothesized: The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.	The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Secondary	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.	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Secondary	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.	The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Secondary	Inflammatory markers at baseline	The investigators hypothesized that: Tumor necrosis factor alpha (TNF-a) and interleukin-6 (IL-6) (both pg/mL) are increased in patients compared to healthy controls.	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Secondary	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)	The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Secondary	Inflammatory markers at follow-up	TNF-a and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.	The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.