Post Concussive SymptomsNCT05812742
Chasing Biomarkers in Post-concussion Syndrome
A study testing Early intervention programme in people with Post Concussive Symptoms, run by University of Aarhus.
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. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Post Concussive Symptoms
- What is being tested?
- Early intervention programme
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 86 participants
- Where
- No sites listed yet
- Study dates
- Mar 2015to Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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).
- 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.
Who cannot join
- 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.
About this study
Official title: Neurofilament Light Chain, Inflammatory Markers, Calcitonin Gene-related Peptide, and Kynurenine Metabolites in Patients With Severe Post-concussive Symptoms
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.
Read the 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.
- Conditions
- Post Concussive Symptoms
- Being tested
- Early intervention programme, Enhanced usual care
- Medical subject headings
- Post-Concussion Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Early intervention programmeBehavioural
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
Enhanced usual careBehavioural
For more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145).
| Study group | Role | What they receive |
|---|---|---|
| Enhanced Usual Care | Active comparator | 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. Receives: Behavioral: Enhanced usual care |
| Enhanced Usual Care + Early intervention programme | Experimental | 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. Receives: Behavioral: Early intervention programme; Behavioral: Enhanced usual care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Measured: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
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.
Measured: 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
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
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Measured: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Secondary outcomes (7)
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
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Quinolinic acid at follow-up
The investigators hypothesized:
The quinolinic acid concentration (nM) normalizes (decreases) at follow-up compared to the baseline concentration.
Measured: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
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.
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Measured: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
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.
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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)
Measured: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Inflammatory markers at follow-up
TNF-α and IL-6 (both pg/mL) decreases at follow-up compared to the baseline value in patients.
Measured: The follow-up blood sample was taken up to 12 months after baseline (7 months median) after the baseline blood sample.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2023
- Study startMar 2015
- Primary completionJul 2023
- Study completionJul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Concussive SymptomsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Sygekassernes Helsefond, Fonden til Lægevidenskabens Fremme, Direktør Emil C. Hertz og Hustru Inger Hertz Fond, Helga Og Peter Kornings Fond, Region MidtJylland Denmark
- Responsible party
- Sponsor
- Investigators
- Peter Preben Eggertsen, MD, Principal investigator, Hammel Neurorehabilitation Centre and University Research Clinic and Research Unit for Molecular Medicine (Aarhus University)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05812742
- Sponsor's protocol ID
- Biomarkers in GAIN 1.0
- Status last verified
- Feb 2023
- First submitted
- 1 Mar 2023
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurofilament Light Chain, Inflammatory Markers, Calcitonin Gene-related Peptide, and Kynurenine Metabolites in Patients With Severe Post-concussive Symptoms
- ClinicalTrials.gov ID
- NCT05812742
- Acronym / sponsor ID
- Biomarkers in GAIN 1.0
- Conditions
- Post Concussive Symptoms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Sygekassernes Helsefond, Fonden til Lægevidenskabens Fremme, Direktør Emil C. Hertz og Hustru Inger Hertz Fond, Helga Og Peter Kornings Fond, Region MidtJylland Denmark
- Study start
- Mar 2015 (actual)
- Primary completion
- Jul 2023 (actual)
- Study completion
- Jul 2023 (actual)
- First posted
- 14 Apr 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Enhanced Usual Care | Active comparator | Behavioral: Enhanced usual careFor 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 | Experimental | Behavioral: Early intervention programme, Behavioral: Enhanced usual careFor 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. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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).
- Age between 18-30 years
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Early intervention programmeFor more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145). | Behavioural | Enhanced Usual Care + Early intervention programme |
| Enhanced usual careFor more information, please go to the original registration of the RCT-study (NCT02337101) or the published article (PMID: 31891145). | Behavioural | Enhanced Usual Care, Enhanced Usual Care + Early intervention programme |
Primary outcome
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.
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.
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.
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
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.
7 secondary outcomes
Quinolinic acid at baseline
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Neuroprotective index at baseline
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Inflammatory markers at baseline
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
Inflammatory markers at baseline
Time frame: The baseline blood sample was taken up to 7 months after the concussion (4 months median).
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Preben Eggertsen, MD principal investigator
Hammel Neurorehabilitation Centre and University Research Clinic and Research Unit for Molecular Medicine (Aarhus University)
Questions about this trial
What is this clinical trial studying?
A study testing Early intervention programme in people with Post Concussive Symptoms, run by University of Aarhus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.