Anxiety Generalized, Breast Cancer Female
Conditions
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.
Interventions
DIETARY_SUPPLEMENTprobiotic 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)
DIETARY_SUPPLEMENTplacebo
Daily consumption of visually similar placebo pills
Sponsors
National Center for Advancing Translational Sciences (NCATS)
Auburn University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
One study staff member will be responsible for randomization and allocation of intervention supplement or placebo, which will be appear to be identical
Intervention model description
Placebo controlled randomized controlled trial
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility - Accrual | 6 months | Number of Participants who were accrued in 6 months |
| Feasibility - Retention | 6 weeks | Retain 85% of randomized participants for duration of study (6 weeks) |
| Feasibility - Adherence | 4 weeks | 80% of participants consuming pills on 90% of intervention days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Inflammatory Marker - LBP | 4 weeks | Serum Lipopolysaccharide Binding Protein |
| Anxiety Symptoms | 4 weeks | Decrease in Generalized Anxiety Disorder-7 (GAD-7) score, which ranges from 0 (no anxiety) to 21 (severe anxiety). |
| Fecal Microbiome Composition | 4 weeks | 16s changes in microbiota alpha diversity |
| Inflammatory Marker - IL-6 | 4 weeks | Pro-inflammatory cytokine, Interleukin-6 (serum) |
| Serotonin | 4 weeks | Serum 5-hydroxytryptamine |
| Inflammatory Marker - TNF-alpha | 4 weeks | Serum Tumor Necrosis Factor-alpha |
Countries
United States
Participant flow
Pre-assignment details
No pre-assignment activities. Participants were randomized and received intervention or treatment immediately after baseline data collection was completed.
Participants by arm
| Arm | Count |
|---|---|
| Synbiotic Supplement Group Daily consumption of pills containing prebiotics and probiotics
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) | 1 |
| Placebo Group Daily consumption of pills containing maltodextrin
placebo: Daily consumption of visually similar placebo pills | 2 |
| Total | 3 |
Baseline characteristics
| Characteristic | Synbiotic Supplement Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 55 years | 62.5 years | 60 years |
| Generalized Anxiety Disorder Screener (GAD-7) Score | 8 units on a scale (min=0; max=21) | 8 units on a scale (min=0; max=21) STANDARD_DEVIATION 4.24 | 8 units on a scale (min=0; max=21) STANDARD_DEVIATION 3 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 2 Participants | 3 Participants |
| Region of Enrollment United States | 1 participants | 2 participants | 3 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 1 | 0 / 2 |
| other Total, other adverse events | 0 / 1 | 0 / 2 |
| serious Total, serious adverse events | 0 / 1 | 0 / 2 |
Outcome results
Primary
Feasibility - Accrual
Number of Participants who were accrued in 6 months
Time frame: 6 months
Population: Number of Participants who were accrued in 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synbiotic Supplement Group | Feasibility - Accrual | 1 Participants |
| Placebo Group | Feasibility - Accrual | 2 Participants |
Primary
Feasibility - Adherence
80% of participants consuming pills on 90% of intervention days
Time frame: 4 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synbiotic Supplement Group | Feasibility - Adherence | 1 Participants |
| Placebo Group | Feasibility - Adherence | 2 Participants |
Primary
Feasibility - Retention
Retain 85% of randomized participants for duration of study (6 weeks)
Time frame: 6 weeks
Population: All participants analyzed
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Synbiotic Supplement Group | Feasibility - Retention | 1 Participants |
| Placebo Group | Feasibility - Retention | 2 Participants |
Secondary
Anxiety Symptoms
Decrease in Generalized Anxiety Disorder-7 (GAD-7) score, which ranges from 0 (no anxiety) to 21 (severe anxiety).
Time frame: 4 weeks
Population: Outcome cannot be reported. Identification of age and race in baseline characteristics with total sample of n=3 compromises personally identifiable information.
Secondary
Fecal Microbiome Composition
16s changes in microbiota alpha diversity
Time frame: 4 weeks
Population: Biospecimen samples will never be analyzed. Data not collected.
Secondary
Inflammatory Marker - IL-6
Pro-inflammatory cytokine, Interleukin-6 (serum)
Time frame: 4 weeks
Population: Biospecimen samples will never be analyzed. Data not collected.
Secondary
Inflammatory Marker - LBP
Serum Lipopolysaccharide Binding Protein
Time frame: 4 weeks
Population: Biospecimen samples will never be analyzed. Data not collected.
Secondary
Inflammatory Marker - TNF-alpha
Serum Tumor Necrosis Factor-alpha
Time frame: 4 weeks
Population: Biospecimen samples will never be analyzed. Data not collected.
Secondary
Serotonin
Serum 5-hydroxytryptamine
Time frame: 4 weeks
Population: Biospecimen samples will never be analyzed. Data not collected.