Aerobic Exercise After Traumatic Brain Injury

Traumatic Brain Injury Clinical Trial

— AER-TBI1  

Official title:

Effects of Aerobic Exercise and Rehabilitation After Traumatic Brain Injury

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT05786729
• Other study ID #: Pro00016168
• Status: Enrolling by invitation
• Phase: Phase 1/Phase 2
• Start date: January 18, 2022
• Est. completion date: January 18, 2028

Study information

• Verified date: March 2023
• Source: Centre for Neuro Skills
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the effects of individualized aerobic exercise regimen on recovery after traumatic brain injury (TBI).Investigators will determine if exercise facilitates recovery by facilitating neuroplasticity and decreasing neuroinflammation.

Description:

Exercise-based therapies can promote recovery of function and are easily implemented in the clinical rehabilitation setting. This study will determine if exercise facilitates recovery by improving markers of neuroplasticity and decreasing neuroinflammatory responses. The investigators will also determine if variations in genes involved in neuroplasticity, and inflammation influence the responsiveness to exercise and rehabilitation. Recovery will be determined by assessing cognitive function, life quality and balance.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 190
• Est. completion date: January 18, 2028
• Est. primary completion date: January 18, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• All participants will provide informed consent and have to comply with the procedures of the study.

• Age will range from 18 to 60 years.

• Except for the non-injured control group, subjects will be required to have experienced TBI.

• All participants should be fluent in English or Spanish.

• All participants should have the ability to comply with the research protocol.

• Capable of exercising in aerobic exercise equipment (with or without trunk support).

• Able to walk independently with or without a device

Exclusion Criteria:

• Current diagnosis of degenerative neurological disease.

• A history of cerebral vascular accidents.

• A history of major psychosis as defined by DSM-IV.

• Subjects receiving physical therapy in a location that is not CNS.

• Pregnancy.

• A history of previous TBI requiring hospitalization.

• Inability to cooperate

• Orthopedic impairment that compromises exercise performance

• Any cardiovascular or respiratory condition that jeopardizes patient health during exercise.

Related Conditions & MeSH terms

• Brain Injuries
• Brain Injuries, Traumatic
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Other:
• Aerobic Exercise (AER)
Aerobic exercise will be performed by utilizing aerobic exercise equipment 3 times per week.
• Rehabilitation
Rehabilitative program is focused on completion of activities of daily living, initiation, appropriate behavior and community integration for five days per week at the Centre for Neuro Skills.

Locations

Country	Name	City	State
United States	Centre for Neuro Skills	Bakersfield	California

Sponsors (2)

Lead Sponsor	Collaborator
Centre for Neuro Skills	University of Pittsburgh

Country where clinical trial is conducted

United States, 

References & Publications (14)

Adlard PA, Perreau VM, Pop V, Cotman CW. Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. J Neurosci. 2005 Apr 27;25(17):4217-21. doi: 10.1523/JNEUROSCI.0496-05.2005. — View Citation

Ashman TA, Gordon WA, Cantor JB, Hibbard MR. Neurobehavioral consequences of traumatic brain injury. Mt Sinai J Med. 2006 Nov;73(7):999-1005. — View Citation

Bland DC, Zampieri C, Damiano DL. Effectiveness of physical therapy for improving gait and balance in individuals with traumatic brain injury: a systematic review. Brain Inj. 2011;25(7-8):664-79. doi: 10.3109/02699052.2011.576306. Epub 2011 May 11. — View Citation

Griesbach GS, Hovda DA, Gomez-Pinilla F. Exercise-induced improvement in cognitive performance after traumatic brain injury in rats is dependent on BDNF activation. Brain Res. 2009 Sep 8;1288:105-15. doi: 10.1016/j.brainres.2009.06.045. Epub 2009 Jun 23. — View Citation

Griesbach GS, Hovda DA, Molteni R, Wu A, Gomez-Pinilla F. Voluntary exercise following traumatic brain injury: brain-derived neurotrophic factor upregulation and recovery of function. Neuroscience. 2004;125(1):129-39. doi: 10.1016/j.neuroscience.2004.01.030. — View Citation

Gurley JM, Hujsak BD, Kelly JL. Vestibular rehabilitation following mild traumatic brain injury. NeuroRehabilitation. 2013;32(3):519-28. doi: 10.3233/NRE-130874. — View Citation

Johnson VE, Stewart W, Smith DH. Axonal pathology in traumatic brain injury. Exp Neurol. 2013 Aug;246:35-43. doi: 10.1016/j.expneurol.2012.01.013. Epub 2012 Jan 20. — View Citation

Kleim JA, Jones TA, Schallert T. Motor enrichment and the induction of plasticity before or after brain injury. Neurochem Res. 2003 Nov;28(11):1757-69. doi: 10.1023/a:1026025408742. — View Citation

Norden DM, Muccigrosso MM, Godbout JP. Microglial priming and enhanced reactivity to secondary insult in aging, and traumatic CNS injury, and neurodegenerative disease. Neuropharmacology. 2015 Sep;96(Pt A):29-41. doi: 10.1016/j.neuropharm.2014.10.028. Epub 2014 Nov 13. — View Citation

Piao CS, Stoica BA, Wu J, Sabirzhanov B, Zhao Z, Cabatbat R, Loane DJ, Faden AI. Late exercise reduces neuroinflammation and cognitive dysfunction after traumatic brain injury. Neurobiol Dis. 2013 Jun;54:252-63. doi: 10.1016/j.nbd.2012.12.017. Epub 2013 Jan 8. — View Citation

Povlishock JT, Pettus EH. Traumatically induced axonal damage: evidence for enduring changes in axolemmal permeability with associated cytoskeletal change. Acta Neurochir Suppl. 1996;66:81-6. doi: 10.1007/978-3-7091-9465-2_15. — View Citation

Rinne MB, Pasanen ME, Vartiainen MV, Lehto TM, Sarajuuri JM, Alaranta HT. Motor performance in physically well-recovered men with traumatic brain injury. J Rehabil Med. 2006 Jul;38(4):224-9. doi: 10.1080/16501970600582989. — View Citation

Schuit AJ, Feskens EJ, Launer LJ, Kromhout D. Physical activity and cognitive decline, the role of the apolipoprotein e4 allele. Med Sci Sports Exerc. 2001 May;33(5):772-7. doi: 10.1097/00005768-200105000-00015. — View Citation

Seifert T, Brassard P, Wissenberg M, Rasmussen P, Nordby P, Stallknecht B, Adser H, Jakobsen AH, Pilegaard H, Nielsen HB, Secher NH. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol. 2010 Feb;298(2):R372-7. doi: 10.1152/ajpregu.00525.2009. Epub 2009 Nov 18. — View Citation

* Note: There are 14 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Aerobic Exercise Induced Changes in Cardio Pulmonary Exercise (CPET) at baseline	CPET will allow us to determine oxygen consumption (VO2). Results will be reported as change in VO2 levels.	Baseline
Primary	Aerobic Exercise Induced Changes in Cardio Pulmonary Exercise (CPET) at Week 4	CPET will allow us to determine oxygen consumption (VO2). Results will be reported as change in VO2 levels.	Week 4
Primary	Aerobic Exercise Induced Changes in Cardio Pulmonary Exercise (CPET) at Week 8	CPET will allow us to determine oxygen consumption (VO2). Results will be reported as change in VO2 levels.	Week 8
Primary	Aerobic Exercise Induced Changes in Cardio Pulmonary (CPET) at Week 12	CPET will allow us to determine oxygen consumption (VO2). Results will be reported as change in VO2 levels.	Week 12
Secondary	Aerobic Exercise Induced Changes in Cognitive Function at baseline	Attention, processing speed, reaction times, memory and nonverbal reasoning are evaluated by CNS Vital Signs. All scores are aggregated to one reported value (Neurocognitive Index). Scoring is by a computer based auto-scored multivariate scoring system developed by the manufacturers.	Baseline
Secondary	Aerobic Exercise Induced Changes in Cognitive Function at Week 4	Attention, processing speed, reaction times, memory and nonverbal reasoning are evaluated by CNS Vital Signs. All scores are aggregated to one reported value (Neurocognitive Index). Scoring is by a computer based auto-scored multivariate scoring system developed by the manufacturers.	Week 4
Secondary	Aerobic Exercise Induced Changes in Cognitive Function at Week 8	Attention, processing speed, reaction times, memory and nonverbal reasoning are evaluated by CNS Vital Signs. All scores are aggregated to one reported value (Neurocognitive Index). Scoring is by a computer based auto-scored multivariate scoring system developed by the manufacturers.	Week 8
Secondary	Aerobic Exercise Induced Changes in Cognitive Function at Week 12	Attention, processing speed, reaction times, memory and nonverbal reasoning are evaluated by CNS Vital Signs. All scores are aggregated to one reported value (Neurocognitive Index). Scoring is by a computer based auto-scored multivariate scoring system developed by the manufacturers.	Week 12
Secondary	Verbal Memory Assessed by the California Verbal Learning Test (CVLT II) at baseline	The California Verbal Learning Test (CVLT II) is a verbal memory cognitive assessment. It assesses repetition learning, serial position effects, semantic organization, intrusions, and proactive interference. CVLT II scores have a mean of 0 and a SD of 1. The range of scores is +5 to -5 reported in increments of .5.	Baseline
Secondary	Verbal Memory Assessed by the California Verbal Learning Test (CVLT II) at Week 4	The California Verbal Learning Test (CVLT II) is a verbal memory cognitive assessment. It assesses repetition learning, serial position effects, semantic organization, intrusions, and proactive interference. CVLT II scores have a mean of 0 and a SD of 1. The range of scores is +5 to -5 reported in increments of .5.	Week 4
Secondary	Verbal Memory Assessed by the California Verbal Learning Test (CVLT II) at Week 8	The California Verbal Learning Test (CVLT II) is a verbal memory cognitive assessment. It assesses repetition learning, serial position effects, semantic organization, intrusions, and proactive interference. CVLT II scores have a mean of 0 and a SD of 1. The range of scores is +5 to -5 reported in increments of .5.	Week 8
Secondary	Verbal Memory Assessed by the California Verbal Learning Test (CVLT II) at Week 12	The California Verbal Learning Test (CVLT II) is a verbal memory cognitive assessment. It assesses repetition learning, serial position effects, semantic organization, intrusions, and proactive interference. CVLT II scores have a mean of 0 and a SD of 1. The range of scores is +5 to -5 reported in increments of .5.	Week 12
Secondary	Quality of Life Measured by the NeuroQOL at baseline	The NeuroQOL assesses quality of life in the domains of Physical Domain, Mental Domain, Cognitive Domain, and Social Domain. Items are scored on a 5-point scale that uses different language depending on assessment. The questions range from least (1) to most (5) based on frequency of behavior, amount of difficulty, or degree of agreement. T-score are used, mean of 50 and SD of 10	Baseline
Secondary	Quality of Life Measured by the NeuroQOL at Week 4	The NeuroQOL assesses quality of life in the domains of Physical Domain, Mental Domain, Cognitive Domain, and Social Domain. Items are scored on a 5-point scale that uses different language depending on assessment. The questions range from least (1) to most (5) based on frequency of behavior, amount of difficulty, or degree of agreement. T-score are used, mean of 50 and SD of 10	Week 4
Secondary	Quality of Life Measured by the NeuroQOL at Week 8	The NeuroQOL assesses quality of life in the domains of Physical Domain, Mental Domain, Cognitive Domain, and Social Domain. Items are scored on a 5-point scale that uses different language depending on assessment. The questions range from least (1) to most (5) based on frequency of behavior, amount of difficulty, or degree of agreement. T-score are used, mean of 50 and SD of 10	Week 8
Secondary	Quality of Life Measured by the NeuroQOL at Week 12	The NeuroQOL assesses quality of life in the domains of Physical Domain, Mental Domain, Cognitive Domain, and Social Domain. Items are scored on a 5-point scale that uses different language depending on assessment. The questions range from least (1) to most (5) based on frequency of behavior, amount of difficulty, or degree of agreement. T-score are used, mean of 50 and SD of 10	Week 12
Secondary	Depression measured by the Beck Depression Inventory-II at baseline	The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: =13 = minimal; 14-19 = mild; 20-28 = moderate; = 29 = severe.	Baseline
Secondary	Depression measured by the Beck Depression Inventory-II at Week 4	The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: =13 = minimal; 14-19 = mild; 20-28 = moderate; = 29 = severe.	Week 4
Secondary	Depression measured by the Beck Depression Inventory-II at Week 8	The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: =13 = minimal; 14-19 = mild; 20-28 = moderate; = 29 = severe.	Week 8
Secondary	Depression measured by the Beck Depression Inventory-II at Week 12	The Beck Depression Inventory- II (BDI-II) assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: =13 = minimal; 14-19 = mild; 20-28 = moderate; = 29 = severe.	Week 12
Secondary	Visual Search/ Processing Speed measured by Trail Making Test (TMT) at baseline	The Trail Making Test (TMT) provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT consists of two parts. TMT-A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-B except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task.	Baseline
Secondary	Visual Search/ Processing Speed measured by Trail Making Test (TMT) at Week 4	The Trail Making Test (TMT) provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT consists of two parts. TMT-A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-B except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task.	Week 4
Secondary	Visual Search/ Processing Speed measured by Trail Making Test (TMT) at Week 8	The Trail Making Test (TMT) provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT consists of two parts. TMT-A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-B except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task.	Week 8
Secondary	Visual Search/ Processing Speed measured by Trail Making Test (TMT) at Week 12	The Trail Making Test (TMT) provides information on visual search, scanning, speed of processing, mental flexibility, and executive functions. The TMT consists of two parts. TMT-A requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for TMT-B except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task.	Week 12
Secondary	Sleepiness will be measured by the Epworth Sleepiness Scale at baseline	The Epworth Sleepiness Scale is used to measure a patient's sleepiness. The test is a list of eight situations in which the patient rates their tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score is based on a scale of 0 to 24. The scale estimates whether you are experiencing excessive sleepiness.	Baseline
Secondary	Sleepiness will be measured by the Epworth Sleepiness Scale at Week 4	The Epworth Sleepiness Scale is used to measure a patient's sleepiness. The test is a list of eight situations in which the patient rates their tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score is based on a scale of 0 to 24. The scale estimates whether you are experiencing excessive sleepiness.	Week 4
Secondary	Sleepiness will be measured by the Epworth Sleepiness Scale at Week 8	The Epworth Sleepiness Scale is used to measure a patient's sleepiness. The test is a list of eight situations in which the patient rates their tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score is based on a scale of 0 to 24. The scale estimates whether you are experiencing excessive sleepiness.	Week 8
Secondary	Sleepiness will be measured by the Epworth Sleepiness Scale at Week 12	The Epworth Sleepiness Scale is used to measure a patient's sleepiness. The test is a list of eight situations in which the patient rates their tendency to become sleepy on a scale of 0, no chance of dozing, to 3, high chance of dozing. Total score is based on a scale of 0 to 24. The scale estimates whether you are experiencing excessive sleepiness.	Week 12
Secondary	Vestibular function will be measured by the Berg Balance Test at baseline	The Berg Balance Scale is used to determine vestibular function through a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.	Baseline
Secondary	Vestibular function will be measured by the Berg Balance Test at Week 4	The Berg Balance Scale is used to determine vestibular function through a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.	Week 4
Secondary	Vestibular function will be measured by the Berg Balance Test at Week 8	The Berg Balance Scale is used to determine vestibular function through a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.	Week 8
Secondary	Vestibular function will be measured by the Berg Balance Test at Week 12	The Berg Balance Scale is used to determine vestibular function through a series of predetermined tasks. It is a 14 item list with each item consisting of a five-point ordinal scale ranging from 0 to 4, with 0 indicating the lowest level of function and 4 the highest level of function.	Week 12
Secondary	Aerobic capacity and endurance will be measured with the 6 Minute Walk Test at baseline	The 6 Minute Walk Test (6MWT) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. A lower score (reflecting less distance covered in 6 minutes) indicates worse function. An increase in the distance walked indicates improvement in basic mobility.	Baseline
Secondary	Aerobic capacity and endurance will be measured with the 6 Minute Walk Test at Week 4	The 6 Minute Walk Test (6MWT) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. A lower score (reflecting less distance covered in 6 minutes) indicates worse function. An increase in the distance walked indicates improvement in basic mobility.	Week 4
Secondary	Aerobic capacity and endurance will be measured with the 6 Minute Walk Test at Week 8	The 6 Minute Walk Test (6MWT) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. A lower score (reflecting less distance covered in 6 minutes) indicates worse function. An increase in the distance walked indicates improvement in basic mobility.	Week 8
Secondary	Aerobic capacity and endurance will be measured with the 6 Minute Walk Test at Week 12	The 6 Minute Walk Test (6MWT) is a exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity. The goal is for the individual to walk as far as possible in six minutes. The individual is allowed to self-pace and rest as needed as they traverse back and forth along a marked walkway. A lower score (reflecting less distance covered in 6 minutes) indicates worse function. An increase in the distance walked indicates improvement in basic mobility.	Week 12
Secondary	Evaluation of Inflammatory Biomarkers at Baseline	Biomarkers IL10, IL12, IL-1ß, IL-4 , IL-5, IL-6, IL-7, IL-8, TNFa, will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Baseline
Secondary	Evaluation of Inflammatory Biomarkers at Week 4	Biomarkers IL10, IL12, IL-1ß, IL-4 , IL-5, IL-6, IL-7, IL-8, TNFa, will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 4
Secondary	Evaluation of Inflammatory Biomarkers at Week 8	Biomarkers IL10, IL12, IL-1ß, IL-4 , IL-5, IL-6, IL-7, IL-8, TNFa, will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 8
Secondary	Evaluation of Inflammatory Biomarkers at Week 12	Biomarkers IL10, IL12, IL-1ß, IL-4 , IL-5, IL-6, IL-7, IL-8, TNFa, will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 12
Secondary	Evaluation of Neuroplasticity, Stress Biomarkers at Baseline	Biomarkers BDNF, GH, ACTH, Cortisol, Melatonin, VEGF will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Baseline
Secondary	Evaluation of Neuroplasticity, Stress Biomarkers at Week 4	Biomarkers BDNF, GH, ACTH, Cortisol, Melatonin, VEGF will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 4
Secondary	Evaluation of Neuroplasticity, Stress Biomarkers at Week 8	Biomarkers BDNF, GH, ACTH, Cortisol, Melatonin, VEGF will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 8
Secondary	Evaluation of Neuroplasticity, Stress Biomarkers at Week 12	Biomarkers BDNF, GH, ACTH, Cortisol, Melatonin, VEGF will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 12
Secondary	Evaluation of Neurodegeneration Biomarkers at Baseline	Biomarkers sCAM1, vCAM-1, sFAS will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Baseline
Secondary	Evaluation of Neurodegeneration Biomarkers at Week 4	Biomarkers sCAM1, vCAM-1, sFAS will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 4
Secondary	Evaluation of Neurodegeneration Biomarkers at Week 8	Biomarkers sCAM1, vCAM-1, sFAS will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 8
Secondary	Evaluation of Neurodegeneration Biomarkers at Week 12	Biomarkers sCAM1, vCAM-1, sFAS will be measured in blood serum before and after a 30 minute aerobic activity. Results will be reported as change in levels.	Week 12
Secondary	BDNF / Val66Met at baseline	Evaluation of genetic material BDNF / Val66Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	BDNF / Val66Met at Week 4	Evaluation of genetic material BDNF / Val66Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	BDNF / Val66Met at Week 8	Evaluation of genetic material BDNF / Val66Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	BDNF / Val66Met at Week 12	Evaluation of genetic material BDNF / Val66Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	IL-1ß / rs16944 at baseline	Evaluation of genetic material IL-1ß / rs16944 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	IL-1ß / rs16944 at Week 4	Evaluation of genetic material IL-1ß / rs16944 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	IL-1ß / rs16944 at Week 8	Evaluation of genetic material IL-1ß / rs16944 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	IL-1ß / rs16944 at Week 12	Evaluation of genetic material IL-1ß / rs16944 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	TrkB at baseline	Evaluation of genetic material TrkB will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	TrkB at Week 4	Evaluation of genetic material TrkB will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	TrkB at Week 8	Evaluation of genetic material TrkB will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	TrkB at Week 12	Evaluation of genetic material TrkB will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	COMT / VAll58Met at baseline	Evaluation of genetic material COMT / VAll58Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	COMT / VAll58Met at Week 4	Evaluation of genetic material COMT / VAll58Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	COMT / VAll58Met at Week 8	Evaluation of genetic material COMT / VAll58Met will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	COMT / VAll58Met at Week 12	Evaluation of genetic material COMT / VAll58Met ewill be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	DRD2 / A to T & A to G at baseline	Evaluation of genetic material DRD2 / A to T & A to G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	DRD2 / A to T & A to G at Week 4	Evaluation of genetic material DRD2 / A to T & A to G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	DRD2 / A to T & A to G at Week 8	Evaluation of genetic material DRD2 / A to T & A to G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	DRD2 / A to T & A to G at Week 12	Evaluation of genetic material DRD2 / A to T & A to G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	ANKKI / TAQIA at baseline	Evaluation of genetic material ANKKI / TAQIA will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	ANKKI / TAQIA at Week 4	Evaluation of genetic material ANKKI / TAQIA will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	ANKKI / TAQIA at Week 8	Evaluation of genetic material ANKKI / TAQIA will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	ANKKI / TAQIA at Week 12	Evaluation of genetic material ANKKI / TAQIA will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	PPPIRIB / C to T at baseline	Evaluation of genetic material PPPIRIB / C to T will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	PPPIRIB / C to T at Week 4	Evaluation of genetic material PPPIRIB / C to T will be measured in a saliva sample. Results will be reported as% difference from the general population.	week 4
Secondary	PPPIRIB / C to T at Week 8	Evaluation of genetic material PPPIRIB / C to T will be measured in a saliva sample. Results will be reported as% difference from the general population.	week 8
Secondary	PPPIRIB / C to T at Week 12	Evaluation of genetic material PPPIRIB / C to T will be measured in a saliva sample. Results will be reported as% difference from the general population.	week 12
Secondary	MAO-A /MAOA-H & MAOA-L at baseline	Evaluation of genetic material MAO-A /MAOA-H & MAOA-L will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	MAO-A /MAOA-H & MAOA-L at Week 4	Evaluation of genetic material MAO-A /MAOA-H & MAOA-L will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	MAO-A /MAOA-H & MAOA-L at Week 8	Evaluation of genetic material MAO-A /MAOA-H & MAOA-Lwill be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	MAO-A /MAOA-H & MAOA-L at Week 12	Evaluation of genetic material MAO-A /MAOA-H & MAOA-L will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	5-HTR2A / AI438G at baseline	Evaluation of genetic material 5-HTR2A / AI438G will be measured in a saliva sample. Results will be reported as % difference from the general population.	Baseline
Secondary	5-HTR2A / AI438G at Week 4	Evaluation of genetic material 5-HTR2A / AI438G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	5-HTR2A / AI438G at Week 8	Evaluation of genetic material 5-HTR2A / AI438G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	5-HTR2A / AI438G at Week 12	Evaluation of genetic material 5-HTR2A / AI438G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	5-HT1A / C1019G at baseline	Evaluation of genetic material 5-HT1A / C1019G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	5-HT1A / C1019G at Week 4	Evaluation of genetic material 5-HT1A / C1019G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	5-HT1A / C1019G at Week 8	Evaluation of genetic material 5-HT1A / C1019G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	5-HT1A / C1019G at Week 12	Evaluation of genetic material 5-HT1A / C1019G will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	5-HTR2B / HTR2B Q20 at baseline	Evaluation of genetic material 5-HTR2B / HTR2B Q20 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	5-HTR2B / HTR2B Q20 at Week 4	Evaluation of genetic material 5-HTR2B / HTR2B Q20 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	5-HTR2B / HTR2B Q20 at Week 8	Evaluation of genetic material 5-HTR2B / HTR2B Q20 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	5-HTR2B / HTR2B Q20 at Week 12	Evaluation of genetic material 5-HTR2B / HTR2B Q20 will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12
Secondary	TPH / A218C & A779C at baseline	Evaluation of genetic material TPH / A218C & A779C will be measured in a saliva sample. Results will be reported as% difference from the general population.	Baseline
Secondary	TPH / A218C & A779C at Week 4	Evaluation of genetic material TPH / A218C & A779C will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 4
Secondary	TPH / A218C & A779C at Week 8	Evaluation of genetic material TPH / A218C & A779C will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 8
Secondary	TPH / A218C & A779C at Week 12	Evaluation of genetic material TPH / A218C & A779C will be measured in a saliva sample. Results will be reported as% difference from the general population.	Week 12