Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03317678 |
| Other study ID # |
16060902 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 10, 2017 |
| Est. completion date |
December 7, 2022 |
Study information
| Verified date |
December 2022 |
| Source |
Rush University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This study aims to assess the impact of a chronic dietary intervention (8 weeks) with
probiotics, specifically Fermented Milk Product with Probiotic (FMPP), on the mood of
individuals with Major Depressive Disorder (MDD) refractory to standard antidepressant
therapy, and its association with changes in intestinal microbiota and markers of
inflammation.
Description:
Theories about the association of imbalances in the gastro-intestinal (GI) microbiota and its
impact on mood states have long existed in medicine. These theories were considered "dead"
for most of the 20th century, but converging lines of evidence are now rekindling interest in
a link between the GI microbiota and the central nervous system. Newer lines of investigation
have made these dormant theories relating commensal microbiota and mood states not only
plausible, but the focus of well-designed basic research studies (Yano et al, 2015; Hsiao et
al, 2013). The microbial world influence on brain development and behavior was defined by Dr
Tom Insel, the former director of the National Institutes of Mental Health as one the "great
frontiers" of neuroscience in the next decade (Insel, 2012). Dr. Francis Collins, Director of
the National Institutes of Health, further underscored the need for research on the impact of
intestinal microbiota on brain function (Collins, 2014).
This renewed interest in understanding the role of the microbiota beyond the digestive tract
was spurred in 2007 when the Human Microbiome Project was launched. (Turnbaugh et al, 2007).
With over one million different genes and a mass equal to that of the human brain, the
genetic diversity of our bacterial commensals outnumbers the human genome by a factor of over
100 to one, and suggests the potential for the genetic variability in the GI environment to
impact other body systems, including the central nervous system (CNS). A range of
neurotransmitters relevant to mood and anxiety disorders including serotonin, GABA,
acetylcholine and endocannabinoids are produced by intestinal microbiota (Dinan et al, 2013).
This accruing data along with previous findings showing that pathological gut bacterium are
capable of inducing changes in behavior (Lyte et al, 1998) and that early life stress, an
established risk factor for major depression, induces changes in the microbiota (O'Mahony et
al, 2007) underscore the potential importance of further examining the relationship between
the microbiota and brain function with particular attention to the potential therapeutic
implications for treatment of psychiatric conditions, such as depression
Preclinical studies demonstrated that noninvasive methods that alter gut microbiota are
capable of inducing antidepressant like effects in rat models of depression (Desbonnet et al,
2010). Findings in human populations showed differences in gut flora of depressed individuals
when compared to healthy controls, including higher levels of Bacteroidetes, Proteobacteria
and Actinobacteria, and a negative correlation between Faecalibacterium and the severity of
their depression (Jiang et al, et al 2015). Other studies point to a beneficial effect of
probiotics on mood and anxiety in normal volunteers (Messaoudi et al, 2011; Benton et al,
2007), as well as in individuals with Irritable Bowel Syndrome (O' Mahoney et al, 2005) and
Chronic Fatigue Syndrome (Rao et al, 2009). However, there have been no systematic studies to
date reporting on the impact of probiotics on mood in individuals with major depression.
The majority of depressed patients remain symptomatic despite treatment with currently
available antidepressants, and a significant proportion do not respond at all. Thus, the
development of new effective antidepressant interventions remains a significant unmet public
health need. Given the accumulating evidence for a relationship between the gastrointestinal
microbiota and the central nervous system functioning and pathophysiology, including that of
affective disorders, it is cogent to measure the impact of probiotic interventions in
individuals with refractory depression. The present study proposes to examine the gut
microbiota, inflammatory milieu and impact of probiotics on mood in a population of
individuals who have been refractory to treatment with standard antidepressant agents.
This study aims to assess the impact of a chronic dietary intervention (8 weeks) with
probiotics, specifically Fermented Milk Product with Probiotic (FMPP), on the mood of
individuals with Major Depressive Disorder (MDD) refractory to standard antidepressant
therapy, and its association with changes in intestinal microbiota and markers of
inflammation.
Specific Aim 1. Examine the effect of 8 weeks of probiotic administration on depressive
symptoms in depressed patients.
Specific Aim 2. Examine the intestinal microbiota at initiation and end of probiotic
administration in order to assess the relationship of baseline and changes in gut flora with
treatment response.
Specific Aim 3. Examine baseline and endpoint inflammatory biomarkers including C-reactive
protein (CRP) and cytokines to assess the relationship of inflammation with intestinal
microbiota and treatment response.
