The Combined Effect of Chronic Cannabis Use and Subconcussive Head Impacts on Brain Health

NCT04641832 | Completed

• 1 other identifier: 2006187939
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this pilot study is to better understand the effects of chronic cannabis (THC) use on the neural responses to subconcussive head impacts, as a form of repetitive soccer headings. The study is designed to identify the physiological changes of cannabis using cohort (THC) and compare it to a nonusing cohort in order to see if the responses to 20 controlled bouts of soccer headings are exacerbated by the chronic cannabis use, diminished to less of a response, or unchanged, through an array of neurologic measures, including cognitive function, ocolar-motor function, autonomic function, and blood biomarkers. The hypothesis is that repetitive subconcussive head impacts will impair cognitive function in worse memory, attention span, and visual and verbal problem solving; this impairment will be greater in the chronic cannabis use groups than non-using group. The blood and salivary biomarkers neurofilament light (NFL) and glial fibrillary acidic protein (GFAP) will be measured in plasma, with the hypothesis that repetitive subconcussive head impacts will significantly increase plasma NFL and GFAP level at 24 hours-post heading and decrease by 72 hours-post heading, while remaining undetectable at 2 hours-post heading; the chronic cannabis use groups will see more severe effects on ocular-motor function than the non-using group. The study aims to determine the differences in acute effects of subconcussive head impacts on eye movement, attention, and language function between chronic cannabis use subjects and non-using subjects by evaluating ocular-motor function with near point of convergence and King-Devick tests. The hypothesis is that repetitive subconcussive head impacts will significantly increase impairments of eye movements, attention, and language function, as well as near point of convergence; the chronic cannabis use groups will see more severe effects on hampered ocular-motor function than the non-using group. Lastly, there is a cold pressor test to assess autonomic nerve function, with the hypothesis that repetitive subconcussive head impacts will decrease autonomic nerve function in chronic cannabis use patients to a greater degree than non-using subjects.

Conditions

Concussion, Mild

Keywords

soccer heading; subconcussive head impacts; cannabis

Outcome Measures

Primary Outcomes (6)

• Acute change in brain-derived blood and saliva biomarkers from pre to 24 hour post-heading

  Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Serum and saliva samples will be aliquoted and stored at -80 degree celsius until analysis. Serum and saliva samples will be assayed for S100B, neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and tau, and UCH-L1. All expression levels in pg/mL.

  Blood samples will be collected at pre- and 24 hour post-heading

• Acute change in brain-derived blood and saliva biomarkers from pre to 2 hour post-heading

  Blood samples will be collected and centrifuged at 1500 x g for ten minutes at 4 degree celsius. Serum and saliva samples will be aliquoted and stored at -80 degree celsius until analysis. Serum and saliva samples will be assayed for S100B, neurofilament-light (NfL), glial fibrillary acidic protein (GFAP), and tau, and UCH-L1. All expression levels in pg/mL.

  Blood and saliva samples will be collected at pre- and 2 hour post-heading

• Acute change in neurocognitive function from pre to 2 hour post-heading

  Participants will complete a computerized neurocognitive assessment (Immediate Post-Concussion Assessment and Cognitive Testing).

  Neurocognitive function will be assessed at pre- and 2 hour post-heading

• Acute change in neurocognitive function from pre to 24 hour post-heading

  Participants will complete a computerized neurocognitive assessment (Immediate Post-Concussion Assessment and Cognitive Testing).

  Neurocognitive function will be assessed at pre- and 24 hour post-heading

• Acute change in ocular-motor function from pre to 2 hour post-heading

  Participants will undergo 2 ocular-motor assessments: 1) near-point of convergence and 2) King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing.

  Ocular-motor function will be assessed at pre- and 2 hour post-heading

• Acute change in ocular-motor function from pre to 24 hour post-heading

  Participants will undergo 2 ocular-motor assessments: 1) near-point of convergence and 2) King-Devick Test--a brief assessment of saccadic eye movements, attention, and visual and language processing.

  Ocular-motor function will be assessed at pre- and 24 hour post-heading

Secondary Outcomes (6)

• Acute change in brain-derived blood and saliva biomarkers from pre to 72 hour post-heading

  Blood and saliva samples will be collected at pre- and 72 hour post-heading

• Acute change in neurocognitive function from pre to 72 hour post-heading

  Neurocognitive function will be assessed at pre- and 72 hour post-heading

• Acute change in ocular-motor function from pre to 72 hour post-heading

  Ocular-motor function will be assessed at pre- and 72 hour post-heading

• Acute change in autonomic nerve function from pre to 2 hour post-heading

  Autonomic response will be assessed at pre- and 2 hour post-heading

• Acute change in autonomic nerve function from pre to 24 hour post-heading

  Autonomic response will be assessed at pre- and 24 hour post-heading

Study Arms (2)

Chronic cannabis use and subconcussive head impacts

EXPERIMENTAL

Group: Chronic cannabis users Criteria: self-reported chronic THC use (average use once per week but not dependent). Urine cannabis test must show positive. Device: Soccer Heading Soccer Heading: Subjects stood approximately 40 feet away from a JUGS soccer ball launcher and participated in 20 consecutive soccer headings, separated by one minute intervals.

Other: Soccer heading

Non-cannabis use and subconcussive head impacts

ACTIVE COMPARATOR

Group: Non cannabis users Criteria: self-reported none THC use. Urine cannabis test must show negative. Device: Soccer Heading Soccer Heading: Subjects stood approximately 40 feet away from a JUGS soccer ball launcher and participated in 20 consecutive soccer headings, separated by one minute intervals.

Other: Soccer heading

Interventions

Soccer heading OTHER

A standardized and reliable soccer heading protocol will be used for the experiment. A triaxial accelerometer embedded in a head-band pocket and positioned directly below the external occipital protuberance (inion) to monitor linear and rotational head accelerations. A JUGS soccer machine will be used to simulate a soccer throw-in with a standardized ball speed of 25mph. The ball speed is similar to when soccer players make a long throw-in from the sideline to mid-field. Soccer players frequently perform this maneuver during practice and games. Subjects will stand approximately 40ft away from the machine to perform the heading. Participants perform 20 standing headers with 1 header per 30 seconds. The subjects will be instructed to direct the ball back toward the JUGS soccer machine in the air.

Chronic cannabis use and subconcussive head impacts; Non-cannabis use and subconcussive head impacts

Eligibility Criteria

• Age: 18 Years - 26 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• For Chronic THC User Group
• being between 18 to 26 years of age
• self-reported chronic THC use (average use once per week but not dependent)3) at least 3 years of soccer heading experience.
• For Non-User Cohort
• being between 18 to 26 years of age
• self-reported non cannabis use in the past 6 months
• at least 3 years of soccer heading experience

You may not qualify if:

• any head, neck, or face injury in the 1 year prior to the study (e.g., concussion, eye injury);
• history of vestibular, ocular, or vision dysfunction (e.g., macular degeneration)
• currently taking any medications affecting balance (e.g., antibiotics)
• pregnancy
• HIV
• any neurological disorders (e.g., seizure disorders, closed head injuries with loss of consciousness greater than 15 minutes, CNS neoplasm, spinal cord injury/surgery, history of stroke)
• hypertension, cardiac arrhythmia, or pulmonary disease
• lower extremity injury that would prohibit performing soccer headings
• metal implants in the head
• used cannabis within the last 72 hours (verified by saliva cannabis test before intervention)
• slept less than 4 hours before the 1st and 2nd test day (verified by screening questionnaire)
• drank any alcoholic drinks or used recreational drugs 72 hours before the 1st test day and during the study period.
• drank more than 3 cups of coffee before any test sessions
• glasses are prohibited (contact lenses are okay) for safety purpose for the heading intervention

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University School of Public Health

Bloomington, Indiana, 47405, United States

Location

MeSH Terms

Conditions

Brain Concussion; Marijuana Abuse

Condition Hierarchy (Ancestors)

Brain Injuries, Traumatic; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Head Injuries, Closed; Wounds and Injuries; Wounds, Nonpenetrating; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Dr. Kawata (PI) will only know subjects' group assignment and ensure blinded experiment and data processing. They will assign participants into two groups, chronic cannabis users and non-users. Group assignment will be based on self-reported cannabis use history and confirmed on 1st day of the study, with a saliva test ensuring no recent (24h-prior) use and a urine test to confirm history of chronic cannabis use or no use. Under the strict supervision of Dr. Kawata, experienced research assistants will perform soccer heading protocol, blood draws, neurocognitive and ocular-motor testing. Statistician will be blinded from group assignment. These processes will ensure single blind method
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: October 30, 2020
• Primary Completion: October 1, 2021
• Study Completion: December 1, 2021
• Last Updated: March 2, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)