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

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.

Study Overview

• Status: Withdrawn
• Conditions: Pain; Anxiety; Surgery
• Intervention / Treatment: Drug: Galacto-Oligosaccharide; Drug: Maltodextrin (Placebo)

Detailed Description

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Galacto-Oligosaccharides (GOS); 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; Mixture produced from lactose utilizing the transgalactosidic activity of Bifidobacterium bifidum NCIMB 41171 beta-galactosidase
Placebo Comparator: Maltodextrin (Placebo); 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); Maltodextrin is a polysaccharide commonly used as a food additive. It is produced from starch by partial hydrolysis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Jeff Taekman, M.D.
• Investigators: Principal Investigator: Jeffrey M Taekman, M.D., Duke University

Publications and helpful links

General Publications

• Schmidt K, Cowen PJ, Harmer CJ, Tzortzis G, Errington S, Burnet PW. Prebiotic intake reduces the waking cortisol response and alters emotional bias in healthy volunteers. Psychopharmacology (Berl). 2015 May;232(10):1793-801. doi: 10.1007/s00213-014-3810-0. Epub 2014 Dec 3.
• Tillisch K. The effects of gut microbiota on CNS function in humans. Gut Microbes. 2014 May-Jun;5(3):404-10. doi: 10.4161/gmic.29232. Epub 2014 May 16.

Study record dates

Study Major Dates

• Study Start (Actual): June 9, 2017
• Primary Completion (Actual): January 1, 2018
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: October 24, 2016
• First Submitted That Met QC Criteria: November 1, 2016
• First Posted (Estimate): November 3, 2016

Study Record Updates

• Last Update Posted (Actual): January 31, 2018
• Last Update Submitted That Met QC Criteria: January 30, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: pain; cognition; surgery; anxiety; perioperative; post operative cognitive dysfunction
• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders
• Other Study ID Numbers: Pro00075000

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