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
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      United States military Veterans from recent conflicts are coping with symptoms related to
      mild traumatic brain injury (mTBI), persistent post concussive (PPC) symptoms, and
      posttraumatic stress disorder (PTSD). Many Veterans are resistant to conventional health and
      mental health interventions (e.g., medication, psychotherapy), and often symptoms are not
      significantly improved by traditional treatments. Moreover, there are limited treatments for
      symptoms associated with both conditions, which frequently co-occur. Alternative treatment
      methods are needed. One potential common underlying feature of both mTBI and PTSD is
      exaggerated inflammation, both peripherally and in the central nervous system, which is
      thought to play an important role in the vulnerability to, aggravation of, and perpetuation
      of adverse consequences of these often co-occurring conditions. Therefore, a novel
      intervention strategy would be the use of immunoregulatory/anti-inflammatory probiotics to
      reduce inflammation. In this study, the investigators will investigate the effects of an
      immunoregulatory probiotic on both biological signatures of systemic inflammatory processes
      and proximal signatures of probiotic administration. Lactobacillus reuteri (L. reuteri), a
      commensal organism that colonizes the human gut mucosa, suppresses mucosal inflammation via
      inhibition of the production of proinflammatory cytokines, and is the probiotic of interest.
      Specific aims of the study are to determine the: 1) effects of L. reuteri on biological
      signatures of gut microbiota, gut permeability, systemic inflammation processes, and stress
      responses; 2) feasibility of L. reuteri supplementation; 3) acceptability of L. reuteri
      supplementation; and 4) tolerability and safety of L. reuteri supplementation. Project aims
      will be assessed using a longitudinal, double blind, randomized placebo-controlled design.
      Participants will be Veterans with PPC symptoms, PTSD, and evidence of elevated systemic
      inflammation (based on high baseline plasma C-reactive protein [CRP] concentrations). After
      initial evaluation procedures, 20 participants will be randomized to probiotic
      supplementation and 20 will be randomized to placebo supplementation. The proposed line of
      research addresses the Office of Rehabilitation Research and Development (RR&D) Service's
      goal of identifying means of intervening to increase function among those with mTBI and
      co-occurring psychiatric conditions. Long-term, this study may lead to a paradigm shift in
      the manner by which the investigators target clinical symptoms associated with PPC and PTSD
      symptoms, by beginning the process of supporting a multitargeted, neuroprotective approach.
    

Intervention name(s): of Lactobacillus reuteri (L. reuteri; DSM 17938); Sunflower and medium chain triglyceride oils
Intervention type(s): Dietary Supplement; Other
Intervention description(s): 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
Other intervention name(s): Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Biologic
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: PTSD; Mild TBI; Probiotic; Inflammation