Amino Acid Supplementation in Recovery From Traumatic Brain Injury

Study Overview
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Brief Summary
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Traumatic brain injury (TBI) is a leading cause of death and disability in young people. It has been called the signature wound of the Iraq war because of its frequency among troops. TBI is associated with many chronic disabilities. Physical alterations include reduced exercise tolerance and profound muscle weakness, whereas psychological alterations include diminished sense of well-being, depression, fatigue and anxiety. Muscle and brain tissues rely upon circulating blood amino acids as precursors for metabolic functions. The investigators have shown that even one year after injury, plasma valine, an essential amino acid (EAA), was markedly reduced in patients with TBI compared to healthy controls. The investigators speculate that low plasma valine concentration contributes to chronic fatigue after TBI, since valine and tryptophan compete for the same transporter into the brain, and a low plasma valine concentration will allow more tryptophan to be transported. As a consequence, increased brain tryptophan will increase serotonin production, which may significantly contribute to the development of fatigue. Thus, the investigators will test if restoring valine concentration in persons with TBI may reduce fatigue perception and improve physical and neuropsychological function. Further, the investigators have previously shown that EAA intake has an anabolic effect in healthy young and elderly individuals. However, no data are currently available in persons recovering from TBI. Thus,the investigators will also test if EAA and/or valine can improve muscle mass in patients with TBI.

Official Title
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Amino Acid Supplementation in Recovery From Traumatic Brain Injury

Conditions
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Traumatic Brain Injury

Intervention / Treatment
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* Dietary Supplement: Amino Acids
* Dietary Supplement: Placebo of inert compounds
* Dietary Supplement: Valine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Presence of traumatic brain injury Age 18-65 years Ability to sign informed consent >3 months post-injury, <36 months post-injury Ambulatory or require minimal to moderate assistance for safe ambulation Exclusion Criteria: Subjects with cardiac abnormalities considered exclusionary by the study physicians Subjects with uncontrolled metabolic disease, including liver or renal disease Subjects with cancer or recently (6 months) treated cancer other than basal cell carcinoma Any subject currently on a weight-loss diet or a body mass index >34 kg/m2 Recent anabolic or corticosteroids use (within 3 months) Dementia Inability to tolerate an upright position Postural reflexes prohibiting ambulation and inability to follow 2-step commands Any other condition or event considered exclusionary by the PIs and covering physician

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Amino acids<br>Amino acid supplementation for 6 weeks | Dietary Supplement: Amino Acids<br>* 15 grams amino acids two times per day for 6 weeks<br>|
| Placebo Comparator: Placebo<br>Supplementation of placebo (inert components)for 6 weeks | Dietary Supplement: Placebo of inert compounds<br>* Placebo two times per day for 6 weeks<br>|
| Active Comparator: Valine<br>Valine supplementation for 6 weeks | Dietary Supplement: Valine<br>* 2.5 grams valine supplementation two times a day for 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Essential Amino Acid Concentrations | TBI patients are deficient in a number of essential amino acids (EAA) post injury and we have shown that TBI patient are deficient in valine up to 17 months post injury. We propose to assess plasma amino acid concentrations in TBI patients who are receiving EAA supplementation or valine supplementation compared to placebo patients. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional impairments | Reduced plasma EAAs may be related to the psychological and metabolic complications associated with TBIs. We aim to assess measures of psychological and physical functionality in TBI patients receiving EAA supplementation. | 6 weeks |