Cognitive and Biological Responses in Stress

Study Overview
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Brief Summary
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The goal of this pilot part of the study (Step 1) is to identify the optimal population of high and low anxiety and stress individuals who will differentially respond to a laboratory stress task as measured by changes in subjective stress response (affect), cognition, attention, and biological measures (autonomic and metabolite responses). Based on experience with different study populations, the investigator's believe that a healthy, homogenous population (Caucasian, women, premenopausal) with higher levels of state anxiety and perceived stress, and with greater responsiveness to laboratory stress tasks (which can also be used in the probiotic intervention study in Step 2) will provide the highest likelihood of identifying the underlying central mechanisms of stress responsiveness in Step 1 and then for the probiotic intervention in Step 2. For this pilot study, the investigator's will look at baseline measures to determine differences in responses to four subjective (affect/cognition/attention) stress tasks (primary endpoints) and biological (secondary endpoints) measures in a high stress group and a low stress group. If for Step 1 of the study, the investigator's are able to verify the stratification of the participants into high and low stress groups based on questionnaire data and show differences between participants with high and low perceived stress in psychological characteristics, lab stress tasks and potentially in biological responses, this will help to determine the optimal cut off values, and the optimal stress tasks to be conducted in the planned probiotic intervention study of Step 2.

Official Title
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Pilot Study Aimed to Determine the Optimal Design for the UCLA/Danone Probiotic Intervention Study Related to Stress

Conditions
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Anxiety, Stress, Psychological

Intervention / Treatment
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* Other: Cognitive Stress Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Caucasian Female 18-45 years of age For the high perceived stress group: a PSS score of 15 or higher and a STAI-S of 39 or higher For the low perceived stress group: a PSS score of 8 or lower and a STAI-S score of 24 or lower Exclusion Criteria: Any ongoing major medical, psychological, or psychiatric conditions and recent changes (3mo) in the use of psychoactive medications or other medications that interfere with the measured outcomes. Medical conditions such as current neurological, cardiovascular, hepatic, renal, autoimmune diseases, diabetes, or cancer. This includes having a current or past within 1 year diagnosis of GI disorders, including but not limited to IBS, IBD, Celiac, or other nutritional deficiency/disease, current eating disorder, or past weight loss surgery. Psychological conditions such as anxiety and depression (I.e., without history of Diagnostic and Statistical Manual (DSM-4) psychiatric diagnosis. Prior/Concomitant Therapy (e.g., Recent changes in the use of psychoactive medications or other medications that interfere with the measured outcomes, as determined by the PI). Subject involved in any other clinical study within the preceding month or in the exclusion period after another clinical study. Positive test for COVID-19 infection in the past month or if presenting symptoms of COVID-19 infection in the past 2 weeks. Diet: Participant who changes her dietary habits within the preceding 4 weeks. Participants on probiotics will be asked to wait 1 month before enrollment in the study. Participant with an eating disorder. Participant with special medicated diet (e.g., for obesity, anorexia, metabolic pathology). Participant under artificial nutrition in the last 1 month. Participant planning to modify her dietary habits during the course of the study. Other Exclusions: Pregnant women or women planning to become pregnant during the study; breast-feeding women based on the interview at screen (Visit 1) and the urine test on day of stress test (Visit 2). Smoker with a moderate to high level of dependence to nicotine (e.g., more than 1/2 a pack of cigarettes a day). Participant consuming regularly more than 3 units of alcohol per day (1 unit = 10mL or 8g). Participants not able to answer questionnaires by writing, whatever the reason. Participant with loos of liberty, by administrative or judicial decision. Participant who is major but with a legal guardian. Participant on antibiotics will be asked to wait 3 months before enrollment in the study. Medications not Authorized: Opiates/Narcotics Chronic/Daily use of analgesics Anti-seizure meds Antidepressants (5HT3's / Tricyclics etc.) are allowed as long as it's been a stable dose for 3 months Medications for ADD/ADHD (I.e., Adderall) Any medication for appetite suppression Chronic use of laxative/antidiarrheals/medications affecting GI motility Insulin Bile acid sequestrants Use of centrally acting medications that will interfere with CNS testing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 groups (high stress/anxiety compared to low stress/anxiety) will be compared on their performance on within laboratory stress and cognitive tasks (4 different tests).
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Stress Group<br>Group of high stress participants based on cutoff scores on the Perceived Stress Scale (PSS) and the STAI - State Anxiety Scale. | Other: Cognitive Stress Testing<br>* Cognitive and stress study with no product intervention and noninvasive. The high stress/anxiety group will be compared to the low stress/anxiety group in terms of changes from baseline to after the cognitive and stress tests (i.e., 4 laboratory tasks) and metabolite measures.<br>* Other names: stress tasks;|
| Experimental: Low Stress Group<br>Group of low stress participants based on cutoff scores on the Perceived Stress Scale (PSS) and the STAI - State Anxiety Scale. | Other: Cognitive Stress Testing<br>* Cognitive and stress study with no product intervention and noninvasive. The high stress/anxiety group will be compared to the low stress/anxiety group in terms of changes from baseline to after the cognitive and stress tests (i.e., 4 laboratory tasks) and metabolite measures.<br>* Other names: stress tasks;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Subjective Stress Response | Between group differences in pre-and post- of the overall negative and positive affect subscale scores from the Positive Affect and Negative Affect Scale (PANAS) administered at baseline immediately before and after the 4 brief and well validated laboratory stress tasks. PANAS scores can range from 10-50 for both the positive and negative affect, with the lower scores representing lower levels of positive/negative affect, and higher scores representing higher levels of positive/negative affect. | Pre and Post laboratory testing during the in-clinic visit lasting 2-4 hours. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Differences in Attention/Executive Function | Between and within group differences on the time it takes to complete the Color Stroop attention/executive function lab stress task. | Throughout the Color Stroop laboratory test at the in-clinic visit lasting approximately 30 minutes. | 
| Differences in Emotional Arousal System | Between and within group differences in valence and emotional arousal ratings during the IAPS task. | Throughout the IAPS laboratory test during the in-clinic visit lasting approximately 30 minutes. | 
| Differences in Subjective Stress Response | Between and within group differences on the negative affect subscale from the Brief Positive Affect and Negative Affect Scale (PANAS) before and after the arithmetic task. PANAS scores can range from 10-50 for both the positive and negative affect, with the lower scores representing lower levels of positive/negative affect, and higher scores representing higher levels of positive/negative affect. | Pre and Post the arithmetic stress task during the in-clinic visit lasting approximately 30 minutes. | 
| Changes in Autonomic Measures - Heart Rate Variability | Between and within group differences in overall average change in heart rate variability pre and post each laboratory stress task. | Throughout each laboratory test during the in-clinic visit lasting 2-4 hours. | 
| Differences in Attention/Executive Function | Between and within group differences on the time it takes to complete the Trails A and B attention/executive function lab stress task. | Throughout the Trails A & B laboratory tests at the in-clinic visit lasting approximately 30 minutes. | 
| Changes in Autonomic Measures - diastolic and systolic blood pressure | Between and within group differences in overall average change in both diastolic and systolic blood pressure pre and post each laboratory stress task. | Throughout each laboratory test during the in-clinic visit lasting 2-4 hours. | 
| Changes in Autonomic Measures - Skin Conductance | Between and within group differences in overall average change in skin conductance pre and post each laboratory stress task. | Throughout each laboratory test during the in-clinic visit lasting 2-4 hours. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stress, women, high stress, low stress, perceived stress