Heading in Football: Impact on Neural Blood Biomarkers (HEADLINE)

The goal of this observational study is to evaluate the safety of heading in football. We will study the release of biomarkers in blood that reflect microscopic neural damage. The main questions this study aims to answer are:

• Does participation in a football match lead to a change in biomarkers that reflect microscopic neural damage?
• Is the dose of exposure during a football match related to the magnitude of change in biomarkers that reflect microscopic neural damage?

Participants will participate in a regular football match and provide blood samples before and right after the football match. The football match will be recorded on video to count the number of headers of all participants.

Study Overview

• Status: Completed
• Conditions: Concussion, Mild; Neurodegeneration; Head Injury, Minor; CTE - Chronic Traumatic Encephalopathy
• Intervention / Treatment: Other: Head impact exposure

Detailed Description

The objective of this prospective observational study is to determine the potential impact of ball heading in football on brain integrity as assessed by blood biomarkers for neural damage in a real-world setting. Healthy amateur football players will be recruited to participate in the study. Participants will be invited to play a regular football match for investigation purposes. They will provide a blood sample within one hour before the start of the match and a second blood sample within one hour after the match. Participants will be asked to provide a third blood sample within 48 hours after participation, but this is not obligatory. The football match will be recorded on video to determine the number of head impacts of all participants. Furthermore, participants will wear heart rate sensors and local positioning sensors to determine the internal and external training load and account for the possible confounding effects of exercise on neural blood biomarkers.

• Study Type: Observational
• Enrollment (Actual): 335

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1105AZ
    • Amsterdam UMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All senior amateur football players will be invited to participate in the study. An amateur population is chosen because of the great number of participants and the resulting societal relevance of the research question.

Description

Inclusion Criteria:

• Member of the KNVB;
• 18 years or older;
• Male
• Self-reported fitness to play 70-90 minutes (absence of injury).

Exclusion Criteria:

• Sustained a head injury in the last year;
• History or current neurological condition;
• Regular participation in other contact sports (e.g. rugby, American football, ice hockey, fighting sports);
• (Former) military personnel with a history of fighting/blast exposure

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Soccer; Healthy volunteers that participate in the study by playing a regular soccer game for the sake of the HEADLINE study	Other: Head impact exposure; The cohort is exposed to naturalistic head impacts (heading) during voluntary participation in a soccer match. All participants are regular soccer players and are therefore not exposed to excessive head impacts compared to their regular exposure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum neurofilament light protein	The difference in serum neurofilament light protein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Concentration of serum S100B protein	The difference in serum S100B protein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)
Concentration of serum p-tau protein	The difference in serum p-tau protein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)
Concentration of serum Neuron Specific Enolase protein	The difference in serum Neuron Specific Enolase protein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)
Concentration of serum Glial Fibrillary Acidic Protein	The difference in serum Glial Fibrillary Acidic Protein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)
Concentration of serum beta-synuclein	The difference in serum beta-synuclein between pre-match samples and post-match samples.	T0 (<1hour pre-match), T1 (<1hour post-match), T2 (<48hour post-match)

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Koninklijke Nederlandse VoetbalBond (KNVB)
• Investigators: Principal Investigator: Jaap Oosterlaan, Prof.Dr., Amsterdam UMC

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2024
• Primary Completion (Actual): December 17, 2024
• Study Completion (Actual): December 17, 2024

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: November 23, 2023
• First Posted (Actual): November 27, 2023

Study Record Updates

• Last Update Posted (Actual): May 13, 2025
• Last Update Submitted That Met QC Criteria: May 8, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Soccer; Neurodegeneration; Heading; Head impact; Blood biomarker
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Pathologic Processes; Chronic Disease; Disease Attributes; Neurodegenerative Diseases; Trauma, Nervous System; Head Injuries, Closed; Wounds, Nonpenetrating; Brain Damage, Chronic; Brain Injuries; Brain Injury, Chronic; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Brain Concussion; Brain Diseases; Craniocerebral Trauma; Nerve Degeneration
• Other Study ID Numbers: NL83396.018.23

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: We intend to make IPD available to other researchers. However, we still need to develop the plan in collaboration with the privacy officer and legal research support.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No