Anti-anxiety Biotics for Breast Cancer Survivors

Study Overview
=================
Brief Summary
-----------------
Cancer survivors experience more rapid declines in health-related quality of life which include physical and psychological comorbidities, the latter of which may be subclinical and often overlooked by primary care providers. Recently, the gut-brain axis (GBA) has been identified as a therapeutic target to improve host health. The GBA is greatly influenced by the composition of the gut microbiome, as microbial metabolites directly influence the central nervous system. Thus, prebiotics, probiotics, and synbiotics (a combination of pre- and probiotics) have emerged as a possible approach to treating anxiety symptoms. Preclinical studies suggest efficacy of synbiotics, while pre- and probiotics have only been studied in isolation in humans. This is a double-blind, placebo-controlled clinical trial in which female breast cancer survivors and/or their female relatives experiencing moderate to severe anxiety symptoms will be randomized to daily consumption of the synbiotic supplement or placebo. The previously validated Generalized Anxiety Disorder-7 (GAD-7) will be used to assess anxiety symptom severity at study screening and at each time point. The primary outcome of this study is feasibility, measured by accrual, adherence, retention, and adverse effects. Secondary outcomes relate to reduction of anxiety symptoms and other physiological changes. No study has investigated the mediating effects of gut microbiota and inflammatory markers on the ability of synbiotics to reduce anxiety symptoms. Thus, at each timepoint, phlebotomy will be conducted to determine serum levels of inflammatory cytokines and stool samples will be collected to determine alpha- and beta-diversity of the fecal microbiome as well as relative abundance of target genera. Hypothesis: this placebo-controlled study will be feasible and synbiotic treatment will result in a significant reduction in anxiety symptoms and inflammatory markers, which may be moderated by changes in the microbiome.

Official Title
-----------------
Synbiotic Supplementation to Reduce Anxiety Symptoms in Female Breast Cancer Survivors and/or Their Female Relatives

Conditions
-----------------
Anxiety Generalized, Breast Cancer Female

Intervention / Treatment
-----------------
* Dietary Supplement: probiotic plus prebiotic supplement
* Dietary Supplement: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Female breast cancer survivors or female relatives of a breast cancer survivor who: are 50 years of age or older have completed primary treatment currently experience clinical anxiety symptoms determined by the 7 item Generalized Anxiety Disorder screener (GAD-7; eligibility requires a total score of 5 or higher on the 21 point scale) agree not to change dietary supplements throughout the course of the study are willing to comply with daily supplement regimen are able to speak and read English. Exclusion Criteria: use of any of the following drugs within the last 4 weeks (unless indefinitely prescribed): systemic antibiotics, corticosteroids, immunosuppressive agents, or commercial probiotics changes in treatment for anxiety symptoms (i.e. initiation of Cognitive Behavior Therapy (CBT) within the last four weeks current use (within 12 weeks) of anxiolytic medications.

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Placebo controlled randomized controlled trial
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Synbiotic supplement group<br>Daily consumption of pills containing prebiotics and probiotics | Dietary Supplement: probiotic plus prebiotic supplement<br>* Daily consumption of probiotic containing at least 5 billion CFU per day total bacteria including Lactobacillus helveticus and Bifidobacterium longum and prebiotic containing 4 grams of fructooligosaccharides (FOS)<br>|
| Placebo Comparator: Placebo group<br>Daily consumption of pills containing maltodextrin | Dietary Supplement: placebo<br>* Daily consumption of visually similar placebo pills<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility - Accrual | Number of Participants who were accrued in 6 months | 6 months | 
| Feasibility - Retention | Retain 85% of randomized participants for duration of study (6 weeks) | 6 weeks | 
| Feasibility - Adherence | 80% of participants consuming pills on 90% of intervention days | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anxiety Symptoms | Decrease in Generalized Anxiety Disorder-7 (GAD-7) score, which ranges from 0 (no anxiety) to 21 (severe anxiety). | 4 weeks | 
| Serotonin | Serum 5-hydroxytryptamine | 4 weeks | 
| Inflammatory Marker - TNF-alpha | Serum Tumor Necrosis Factor-alpha | 4 weeks | 
| Inflammatory Marker - LBP | Serum Lipopolysaccharide Binding Protein | 4 weeks | 
| Inflammatory Marker - IL-6 | Pro-inflammatory cytokine, Interleukin-6 (serum) | 4 weeks | 
| Fecal Microbiome Composition | 16s changes in microbiota alpha diversity | 4 weeks |