Biological Signatures, Probiotic Among Those With mTBI and PTSD
Condition: Mild Traumatic Brain Injury; Post Traumatic Stress Disorder
MeSH terms: Brain Injuries; Brain Injuries, Traumatic; Brain Concussion; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
Intervention: of Lactobacillus reuteri (L. reuteri; DSM 17938); Sunflower and medium chain triglyceride oils
Intervention description: Commercially available L. reuteri (deposited in the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSMZ) and referenced as DSM 17938; Gerber Soothe Colic Drops, 100 million CFU/5 drops; formerly known as L. reuteri ATCC 55730) will be used in the proposed study. L. reuteri (phylum Firmicutes) is a gram-positive anaerobic commensal bacteria found in the gut microbiome of humans. Independent testing of the viability of the commercial product will be conducted in our laboratories by diluting drops, plating on agar in triplicate, and anaerobic culturing at 37 oC. The commercial strain (DSM 17938) has been used to improve intestinal functions in infants and reduce symptoms of infantile colic.; Placebo
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Biologic
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 75.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: No
Keywords: PTSD; Mild TBI; Probiotic; Inflammation

Summary:

      Exaggerated inflammation in the body and brain is thought to play a role in the vulnerability
      to and aggravation and perpetuation of adverse consequences among those with co-occurring
      mild TBI (mTBI) and post-traumatic stress disorder (PTSD). The proposed study begins the
      process of investigating the use of a natural immunoregulatory/anti-inflammatory probiotic to
      treat chronic symptoms associated with co-occurring mTBI and PTSD among Veterans. By looking
      at the impact of probiotic supplementation on biological signatures of increased
      inflammation, as reflected by the gut microbiota, gut permeability, and biomarkers of
      peripheral inflammation, this study may lead to the identification of a novel intervention
      for the treatment of symptoms associated with these frequently co-occurring conditions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  History of at least one deployment in support of Operation Enduring Freedom
             (OEF)/Operation Iraqi Freedom (OIF)/Operation New Dawn (OND)

          -  History of mTBI per the Ohio State University (OSU) TBI-ID85 with any endorsement of
             post concussive symptoms (PCS) associated with an mTBI, which occurred at least 6
             months prior to the baseline assessment

          -  Current symptoms in 3 or more of the following ICD-10 Post Concussive Symptom86
             categories as measured by the Rivermead Post Concussive Symptom Questionnaire
             (RPCSQ87; score of 2 or greater per symptom to qualify):

               -  headache

               -  dizziness

               -  malaise

               -  fatigue

               -  noise intolerance

               -  irritability

               -  depression

               -  anxiety

               -  emotional lability

               -  subjective concentration

               -  memory

               -  intellectual difficulties

               -  and/or insomnia

          -  Current diagnosis of PTSD per the Clinician Administered PTSD Scale-5 (CAPS-5)88

          -  Medical clearance by study physicians to participate in the protocol

          -  Age between 18 and 50

          -  Ability to provide informed consent

          -  Willingness not to take probiotic supplements (pills, tablets, oils, etc.) other than
             the product provided in the clinical study until all study procedures are completed

          -  Willingness to provide blood, as well as stool samples

        Exclusion Criteria:

          -  Inability to adequately respond to questions regarding the informed consent procedure

          -  Currently involved in the criminal justice system as a prisoner or ward of the state

          -  Non-English speaking

          -  Current (past month) alcohol or substance abuse or dependence

          -  Lifetime history of bipolar disorder or psychosis or anxiety disorders (excluding
             PTSD)

          -  Current major depressive disorder (MDD)

          -  Consistent (e.g., 5x/week or greater) probiotic supplementation within the last month,
             including probiotic food products such as yogurt, as determined by phone screen
             interview and Probiotic Food Check List

          -  Receiving antibiotics within the last month; use of topical antibiotics or topical
             steroids on the face, scalp, or neck or on arms, forearms, or hands within the
             previous 7 days

          -  Receiving medications that interfere with gut motility (opiates, loperamide, stool
             softeners)

          -  Presence of central venous catheters (CVCs)

          -  Gastrointestinal (GI) barriers as identified by the 2-week run-in period as determined
             by the study team (e.g., daily GI discomfort with frequent diarrhea prior to
             supplementation)

          -  Participation in conflicting interventional research protocol

          -  Body mass index (BMI) greater than or equal to 35 or less than or equal to 18

          -  Vital signs outside of acceptable range, i.e., blood pressure >160/100, oral
             temperature >100 F, pulse >100

          -  Use of any of the following drugs within the last 6 months:

               -  systemic antibiotics

               -  antifungals

               -  antivirals or antiparasitics (intravenous, intramuscular, or oral)

               -  oral

               -  intravenous

               -  intramuscular

               -  nasal or inhaled corticosteroids

               -  cytokines or cytokine inhibitors

               -  methotrexate or immunosuppressive cytotoxic agents

          -  Acute disease at the time of enrollment (defer sampling until subject recovers)

               -  Acute disease is defined as the presence of a moderate or severe illness with or
                  without fever

          -  Chronic, clinically significant (unresolved, requiring on-going medical management or
             medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional
             abnormality, as determined by medical history or physical examination other than
             irritable bowel syndrome (IBS)

          -  History of cancer except for squamous or basal cell carcinomas of the skin that have
             been medically managed by local excision

          -  Unstable dietary history as defined by major changes in diet during the previous
             month, where the subject has eliminated or significantly increased a major food group
             in the diet

          -  Positive test for human immunodeficiency virus (HIV), Hepatitis B virus, or Hepatitis
             C virus

          -  Any confirmed or suspected condition/state of immunosuppression or immunodeficiency
             (primary or acquired) including HIV infection

          -  Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy,
             in the past five years. Any major bowel resection at any time

          -  Regular urinary incontinence necessitating use of incontinence protection garments

          -  Female who is pregnant or lactating

          -  Treatment for or suspicion of ever having had toxic shock syndrome

          -  Those receiving immunosuppressive drugs or treatment including antineoplastic therapy,
             post-transplantation immunosuppressive therapy, and/or radiation therapy