Exploring the Impact of Perioperative Galacto-Oligosaccharides (GOS) on Stress, Anxiety and Cognition

Study Overview
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Brief Summary
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The overall objective of this proposal is to explore the association between the administration of the prebiotics GOS (trade name: Bimuno Travelaid; generic name:B galacto-oligosaccharides) with pain, anxiety, and cognitive function in the perioperative period. The investigators' central hypothesis is subjects who consume GOS in the perioperative period will demonstrate lower levels of salivary cortisol before, during, and after their operative procedures. In addition, the investigators expect subjects who consume GOS to have lower perceived levels of anxiety during the perioperative period. Finally, the investigators hypothesize that subjects who consume perioperative GOS will perform better on tests of cognition in the postoperative period. Such a finding would be beneficial in that administration of GOS in the perioperative period offers a safe and inexpensive adjunct to current medical management of perioperative anxiety.

Detailed Description
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AIM 1: In anterior cervical decompression and fusion (ACDF) subjects, explore the association between prebiotics, anxiety, and pain. Studies have recently elucidated a link between certain prebiotics and lower perceived anxiety as well as biomarkers of stress. In this aim the investigators will explore the association between consumption of prebiotics and their relationship to perioperative anxiety / physiological stress response. The investigators hypothesize that subjects who receive prebiotics will have lower perioperative anxiety and stress versus control as measured by standardized surveys and biomarkers. Furthermore, the investigators hypothesize that lower anxiety will result in lower postoperative pain scores. AIM 2: In ACDF patients, explore the association between GOS and post-operative cognitive dysfunction. Stress and anxiety is known to impair cognitive function. In addition, in preclinical studies, the administration of distinct keystone bacterial strains improves cognitive function in an anxious mouse model. In humans, prebiotics and probiotics have been shown to ameliorate the stress response. In this aim the investigators seek to explore the association between prebiotics and perioperative cognitive outcomes in humans. The investigators will perform cognitive function testing using the same time-tested battery used in the department to study post-operative cognitive decline (POCD). Subjects will be tested for cognitive function preoperatively (T1) and at 1.5 months post-op (T4). The investigators hypothesize that patients receiving prebiotics during the perioperative period will show less post-operative cognitive dysfunction than controls. A total of 8 subjects will be recruited from the Neurosurgery Clinics of Duke University Health System. The target population will include subjects undergoing ACDF. Exclusion criteria will include: pregnant women, age<21 years, a diagnosis of depression, mental or behavioral disorder, recent anxiolytic use, long-term opiate use, oral contraceptive use, or recent antibiotic use.

Official Title
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Exploring the Impact of Perioperative Galacto-Oligosaccharides (GOS) on Stress, Anxiety and Cognition

Conditions
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Anxiety, Pain, Surgery

Intervention / Treatment
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* Drug: Galacto-Oligosaccharide
* Drug: Maltodextrin (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients undergoing anterior cervical discectomy and fusion Exclusion Criteria: Pregnancy Breast Feeding Women Diagnosis of Depression Diagnosis of mental or behavioral disorder Recent anxiolytic use (within 1 week of enrollment) Long-term opiate use (greater than 1 week prior to enrollment) Recent systemic steroid use (within 1 week of enrollment) Diagnosis of cancer Oral or intravenous antibiotic use within 1 month of enrollment

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Galacto-Oligosaccharides (GOS)<br>Clasado Biosciences Limited will provide Bimuno Pastilles for the clinical trial. Each pastille contains 0.92g GOS and will be taken 3 times per day. Following informed consent, subjects will be issued prepackaged GOS pastilles to be taken three times daily up until the evening prior to surgery. Subjects will be randomly assigned to receive GOS prebiotics. Each subject has an equal chance of receiving GOS or placebo. GOSn will be administered in the hospital when patient reinstitutes oral intake. GOS will be issued to each subject to last until the day of their scheduled follow-up for POCD (approximately 1.5 months post surgery). | Drug: Galacto-Oligosaccharide<br>* Mixture produced from lactose utilizing the transgalactosidic activity of Bifidobacterium bifidum NCIMB 41171 beta-galactosidase<br>|
| Placebo Comparator: Maltodextrin (Placebo)<br>Clasado Biosciences Limited will provide placebo (Maltodextrin) for the clinical trial. Each pastille contains maltodextrin and will be taken 3 times per day. Following informed consent, subjects will be issued prepackaged pastilles to be taken three times daily up until the evening prior to surgery. Subjects will be randomly assigned to receive GOS prebiotics or placebo. Each subject has an equal chance of receiving GOS or placebo. Placebo will be administered in the hospital when patient reinstitutes oral intake. Placebo will be issued to each subject to last until the day of their scheduled follow-up for POCD (approximately 1.5 months post surgery). | Drug: Maltodextrin (Placebo)<br>* Maltodextrin is a polysaccharide commonly used as a food additive. It is produced from starch by partial hydrolysis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Waking Salivary Cortisol |  | Morning after Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 1-day after surgery, 6-week follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in pain perception | Collected through Visual Analog Scale. | Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 30 minutes after surgery, 1-day after surgery, 6 week follow-up visit | 
| Changes in cognition | Hopkins Verbal Learning Test - Revised (HVLT-R) | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in perceived stress | Subjects will complete web-based versions of the State-Trait Anxiety Scale. | Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 1-day after surgery, 6 week follow-up visit | 
| Changes in perceived stress | Subjects will complete web-based versions Hospital Anxiety and Depression Scale-HADS. | Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 1-day after surgery, 6 week follow-up visit | 
| Changes in perceived stress | Subjects will complete web-based versions Visual Analog Anxiety Scale. | Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 30 minutes after surgery, 1-day after surgery, 6 week follow-up visit | 
| Changes in cognition | Randt Short Story Memory Test | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in cognition | Modified Visual Reproduction Test from the Wechsler Memory Scale | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in cognition | Weschsler Adult Intelligence Scale - Revised (WAIS-R) | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in cognition | Trail Making Test | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in cognition | Grooved Pegboard | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Changes in cognition | Mini Mental Status Exam (MMSE) | Preop Clinic Visit (2 weeks prior to surgery), 6 week follow-up visit | 
| Suicidal ideation and behavior | Columbia-Suicide Severity Rating Scale (C-SSRS) | Preop Clinic Visit (2 weeks prior to surgery), 2-hours before surgery, 1-day after surgery, 6 week follow-up visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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perioperative, surgery, pain, anxiety, post operative cognitive dysfunction, cognition