Chasing Biomarkers in Post-concussion Syndrome
- Conditions
- Post Concussive Symptoms
- Interventions
- Behavioral: Early intervention programmeBehavioral: Enhanced usual care
- Registration Number
- NCT05812742
- Lead Sponsor
- University of Aarhus
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 86
- 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).
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Enhanced Usual Care + Early intervention programme Early intervention programme 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. Enhanced Usual Care Enhanced usual care 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. Enhanced Usual Care + Early intervention programme Enhanced usual care 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.
- Primary Outcome Measures
Name Time Method Neurofilament light chain at baseline (primary outcome) 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.Neurofilament light chain at follow-up (primary outcome) 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.Self-reported post-concussion symptoms score (primary outcome) 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.Calcitonin-gene related peptide at follow-up (CGRP) 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.Calcitonin-gene related peptide at baseline (CGRP) 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
- Secondary Outcome Measures
Name Time Method Neuroprotective index at baseline 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.Quinolinic acid at baseline 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 controlsQuinolinic acid at follow-up 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.Neuroprotective index at follow-up 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.Inflammatory markers at baseline 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)Inflammatory markers at follow-up 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.