Anti-anxiety Biotics for Breast Cancer Survivors (ABBCS)

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

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.

Study Overview

• Status: Terminated
• Conditions: Breast Cancer Female; Anxiety Generalized
• Intervention / Treatment: Dietary supplement: probiotic plus prebiotic supplement; Dietary supplement: placebo

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Auburn, Alabama, United States, 36849
      • Auburn University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Female breast cancer survivors or female relatives of a breast cancer survivor who:

1. are 50 years of age or older
2. have completed primary treatment
3. 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)
4. agree not to change dietary supplements throughout the course of the study
5. are willing to comply with daily supplement regimen
6. are able to speak and read English.

Exclusion Criteria:

1. use of any of the following drugs within the last 4 weeks (unless indefinitely prescribed): systemic antibiotics, corticosteroids, immunosuppressive agents, or commercial probiotics
2. changes in treatment for anxiety symptoms (i.e. initiation of Cognitive Behavior Therapy (CBT) within the last four weeks
3. current use (within 12 weeks) of anxiolytic medications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Synbiotic supplement group; Daily consumption of pills containing prebiotics and probiotics	Dietary supplement: probiotic plus prebiotic supplement; 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)
Placebo Comparator: Placebo group; Daily consumption of pills containing maltodextrin	Dietary supplement: placebo; Daily consumption of visually similar placebo pills

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
Serotonin	Serum 5-hydroxytryptamine	4 weeks
Anxiety Symptoms	Decrease in Generalized Anxiety Disorder-7 (GAD-7) score, which ranges from 0 (no anxiety) to 21 (severe anxiety).	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

Collaborators and Investigators

• Sponsor: Auburn University
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Andrew D Frugé, PhD, Auburn University

Publications and helpful links

General Publications

• Smith KS, Greene MW, Babu JR, Fruge AD. Psychobiotics as treatment for anxiety, depression, and related symptoms: a systematic review. Nutr Neurosci. 2021 Dec;24(12):963-977. doi: 10.1080/1028415X.2019.1701220. Epub 2019 Dec 20.

Helpful Links

• Study website

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2021
• Primary Completion (Actual): May 1, 2022
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 2, 2021
• First Posted (Actual): March 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 24, 2023
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Anxiety Disorders
• Other Study ID Numbers: 21-110; UL1TR003096-03 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No