Clinical trial NCT06270680: Carotenoids for Collision Athletes
Official title: Efficacy of Carotenoids on Blood Biomarkers Following A Collision Sport Athletes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Head Injury
Carotenoids
Keywords: Carotenoids
Brain injury
Head impacts
Vision
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: MacuHealth
name: Orlando Regional Medical Center
First posted: 2024-02-21
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: This is a supplement study being conducted to find out if collision sport athletes who are exposed to repetitive head impacts while supplementing with carotenoids will have decreased pro-inflammatory blood biomarkers, increases in macular pigment optical density, improved contrast sensitivity, greater retinal nerve fiber thickness, and better overall visual quality of life scores compared to collision athletes taking a placebo.

Detailed description: Originally adapted to augment macular pigment for anti-inflammatory, antioxidative, blue light, and visual performance purposes, supplementation with carotenoids has been tested in animal models for protective effects against traumatic brain injury (TBI). Results have been promising, as mice provided with the three main carotenoids (Lutein, Meso-Zeaxanthin, and Zeaxanthin) following TBI displayed reduced levels of pro-inflammatory markers (IL-1β, IL-6, and GFAP) and increased levels of GAP43, NCAM, and BDNF, signaling activation of anti-oxidant systems.

Due to inflammation of the visual system following trauma, immune responses in the eye are for both reparative and protective purposes. However, cytokines released by immune cells compromise visual acuity by means of inflammation and fibrosis (scarring). As such, inflammation to the visual system (including visual processing structures in the brain) carries the danger of visual impairment. Research examining chronic inflammatory responses in the optic tract and subsequent visual dysfunction found mTBI in rodent models to increase GFAP, tumor necrosis factor (TNF), and degeneration of axons up to 3.5 months post-injury. As such, inflammation of the visual system is a measurable phenomenon in rodent models, conveying the need for human subjects research. The nutrients found in the proposed test supplement, lutein, zeaxanthin, meso-zeaxanthin, along with the omega-3 fatty acids DHA and EPA, are deposited in the brain regions that are often found to be affected by a collision-related head injury. Thus, an exploratory study of this topic is proposed, utilizing the three main carotenoids in the form of a MacuHealth supplement.

Optical Coherence Tomography has become a critical clinical tool when discovering and diagnosing disease and neurological disorders of the eyes. It works to map the retina in order to give ophthalmologists precise measurements of the tissues which make up this important part of human anatomy and helps medical experts to diagnosis diseases of the eye such as Glaucoma and Macular Degeneration. In terms of retinal nerve fiber layer thickness (RNFL), a study found Olympic boxers to have thinner RNFL compared to controls. Another study found RNFL thickness as a significant predictor of athlete vs control status, with 4.8-um of thinning seen on average in athletes (boxing, football) when compared to controls.

Although vision disorders are so common, VQOL - to our knowledge - is not specifically addressed following exposure to repetitive head impacts (RHI), concussion, or during return-to-play protocol. In sports such as football, hockey, and boxing where participants are exposed to RHI, participation while experiencing decreased VQOL or visual functionality could prove costly to the health of those athletes. Poor visual acuity and photophobia following concussion have been cited as indicators of poor VQOL. As such, use of the VFQ-25 and the 10-Item Supplement may be important additions to current clinical practice when evaluating the baseline health status of athletes, and following the completion of a collision-sport season.

Eligibility criteria: Inclusion Criteria:

* Collision sport athletes:

  1. Penn State student ages 18 and over
  2. Any gender
  3. Participating in club, or intramural collision-sports and is willing to participate in this study (examples: hockey, lacrosse, soccer, wrestling, rugby, boxing, basketball, cheer).

Exclusion Criteria:

* For all subjects:

  1. Subjects with concurrent injury that would impair their ability to perform the assigned procedures will be excluded.
  2. Under 18 years of age.
  3. Not a Penn State Student
  4. Not participating in a collision sport.
  5. Diagnosis of a learning disability impacting their capacity to consent.
  6. History of ocular or neurological disease (glaucoma, macular degeneration, MS, Parkinson's)
  7. Concussion diagnosis within the last calendar year.
* However, if a subject sustains a concussion during the course of the study, they may remain as an active participant if they wish to do so.

Primary outcomes:
measure: Blood and saliva biomarkers via venous blood draw and spitting into sterile cup.
timeFrame: Up to 16 weeks
measure: Visual Performance: Speed of visual processing
timeFrame: Up to 16 weeks
measure: Visual Performance: Contrast Sensitivity
timeFrame: Up to 16 weeks
measure: Skin carotenoid concentration
timeFrame: Up to 16 weeks
measure: Retinal Nerve Fiber Layer Thickness
timeFrame: Up to 16 weeks
measure: Macular Pigment Optical Density
timeFrame: Up to 16 weeks
measure: Visual Quality of Life Scores
timeFrame: Up to 16 weeks
measure: Visual Quality of Life Scores
timeFrame: Up to 16 weeks
Secondary outcomes:
measure: Demographic information
timeFrame: Up to 16 weeks
measure: Demographic information
timeFrame: Up to 16 weeks
Other outcomes:
Locations:
city: University Park
country: United States
facility: The Pennsylvania State University
state: Pennsylvania
Study officials:
affiliation: The Pennsylvania State University
name: Semyon Slobounov, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stringham JM, Hammond BR. Macular pigment and visual performance under glare conditions. Optom Vis Sci. 2008 Feb;85(2):82-8. doi: 10.1097/OPX.0b013e318162266e.
citation: Stringham JM, Stringham NT, O'Brien KJ. Macular Carotenoid Supplementation Improves Visual Performance, Sleep Quality, and Adverse Physical Symptoms in Those with High Screen Time Exposure. Foods. 2017 Jun 29;6(7):47. doi: 10.3390/foods6070047.
citation: Stringham JM, Johnson EJ, Hammond BR. Lutein across the Lifespan: From Childhood Cognitive Performance to the Aging Eye and Brain. Curr Dev Nutr. 2019 Jun 4;3(7):nzz066. doi: 10.1093/cdn/nzz066. eCollection 2019 Jul.
citation: Gunal MY, Sakul AA, Caglayan AB, Erten F, Kursun OED, Kilic E, Sahin K. Protective Effect of Lutein/Zeaxanthin Isomers in Traumatic Brain Injury in Mice. Neurotox Res. 2021 Oct;39(5):1543-1550. doi: 10.1007/s12640-021-00385-3. Epub 2021 Jun 15.
citation: Stepp MA, Menko AS. Immune responses to injury and their links to eye disease. Transl Res. 2021 Oct;236:52-71. doi: 10.1016/j.trsl.2021.05.005. Epub 2021 May 27.
citation: Chen JJ, Bhatti MT. Papilledema. Int Ophthalmol Clin. 2019 Summer;59(3):3-22. doi: 10.1097/IIO.0000000000000274. No abstract available.
citation: Vishwanathan R, Neuringer M, Snodderly DM, Schalch W, Johnson EJ. Macular lutein and zeaxanthin are related to brain lutein and zeaxanthin in primates. Nutr Neurosci. 2013 Jan;16(1):21-9. doi: 10.1179/1476830512Y.0000000024. Epub 2012 Jul 9.
citation: Strong J. Retinal OCT Imaging - Ophthalmic Photographers' Society. Published 2011. Accessed January 5, 2023. https://www.opsweb.org/page/RetinalOCT
citation: Childs C, Barker LA, Gage AM, Loosemore M. Investigating possible retinal biomarkers of head trauma in Olympic boxers using optical coherence tomography. Eye Brain. 2018 Dec 14;10:101-110. doi: 10.2147/EB.S183042. eCollection 2018.
citation: Leong D, Morettin C, Messner LV, Steinmetz RJ, Pang Y, Galetta SL, Balcer LJ. Visual Structure and Function in Collision Sport Athletes. J Neuroophthalmol. 2018 Sep;38(3):285-291. doi: 10.1097/WNO.0000000000000572.
citation: Armstrong RA. Visual problems associated with traumatic brain injury. Clin Exp Optom. 2018 Nov;101(6):716-726. doi: 10.1111/cxo.12670. Epub 2018 Feb 28.