Metagenomic and Metabolomic Reconstitution of Gut Microbiota After Broad Spectrum Antibiotic Therapy

NCT ID: NCT04171466

Last Updated: 2022-10-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

46 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-08-12

Study Completion Date

2022-09-07

Brief Summary

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In the United States, healthcare providers prescribe over 270 million antibiotic prescriptions each year. While antibiotics have transformed medicine and methods of treating life-threatening bacterial infection, broad spectrum antibiotics also induce disruption of resident gut microbial communities by altering both composition and function. This disruption of microbial community dynamics has been demonstrated at the taxonomic level, yet the extent of functional disruptions to microbial metabolic output and host cells remains understudied in humans. This study explores the impact of a broad spectrum antibiotic cocktail on microbial communities throughout the gastrointestinal tract, and the impact of a defined, multi-strain consortia of probiotic organisms following antibiotic exposure.

Detailed Description

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Conditions

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Antibiotic Side Effect Antibiotic-associated Diarrhea Antibiotic-induced Dysbiosis Antibiotic-induced Epithelial Barrier Disintegrity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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Broad Spectrum Antibiotic Therapy + Microbial Consortia

Group Type ACTIVE_COMPARATOR

Ciprofloxacin + Metronidazole

Intervention Type OTHER

Participants will be instructed to take 1 capsule of Ciprofloxacin (500mg) twice daily for 7 days and 1 capsule of Metronidazole (500mg) thrice daily for 7 days. Antibiotics should be taken at least 2 hours before or 6 hours after mineral supplements containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc.

SH-DS01

Intervention Type OTHER

SH-DS01 is a rationally defined microbial consortia consisting of 24 strains across 12 species, with polyphenolic and phenolic prebiotic bioactive compounds. Participants will be instructed to take 2 capsules daily for the duration of the trial.

Broad Spectrum Antibiotic Therapy + Placebo

Group Type PLACEBO_COMPARATOR

Ciprofloxacin + Metronidazole

Intervention Type OTHER

Participants will be instructed to take 1 capsule of Ciprofloxacin (500mg) twice daily for 7 days and 1 capsule of Metronidazole (500mg) thrice daily for 7 days. Antibiotics should be taken at least 2 hours before or 6 hours after mineral supplements containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc.

Placebo

Intervention Type OTHER

Placebo capsules for SH-DS01 will contain rice flour matched for color and texture in an identical outer capsule shell. Participants will be instructed to take 2 capsules daily for the duration of the trial.

No Antibiotic Therapy + Microbial Consortia

Group Type ACTIVE_COMPARATOR

SH-DS01

Intervention Type OTHER

SH-DS01 is a rationally defined microbial consortia consisting of 24 strains across 12 species, with polyphenolic and phenolic prebiotic bioactive compounds. Participants will be instructed to take 2 capsules daily for the duration of the trial.

No Antibiotic Therapy + Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Placebo capsules for SH-DS01 will contain rice flour matched for color and texture in an identical outer capsule shell. Participants will be instructed to take 2 capsules daily for the duration of the trial.

Interventions

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Ciprofloxacin + Metronidazole

Participants will be instructed to take 1 capsule of Ciprofloxacin (500mg) twice daily for 7 days and 1 capsule of Metronidazole (500mg) thrice daily for 7 days. Antibiotics should be taken at least 2 hours before or 6 hours after mineral supplements containing magnesium or aluminum, as well as sucralfate, metal cations such as iron, and multivitamin preparations with zinc.

Intervention Type OTHER

SH-DS01

SH-DS01 is a rationally defined microbial consortia consisting of 24 strains across 12 species, with polyphenolic and phenolic prebiotic bioactive compounds. Participants will be instructed to take 2 capsules daily for the duration of the trial.

Intervention Type OTHER

Placebo

Placebo capsules for SH-DS01 will contain rice flour matched for color and texture in an identical outer capsule shell. Participants will be instructed to take 2 capsules daily for the duration of the trial.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

1. Males \& Females 18-55 years of age, inclusive
2. BMI of 18.5 - 29.9 kg/m2, inclusive
3. Waist circumference \< 102 cm in males or \< 88 cm in females
4. Female participant is not of child-bearing potential, defined as females who have undergone a sterilization procedure (e.g. hysterectomy, bilateral oophorectomy, bilateral tubal ligation, total endometrial ablation) Or, Females of child-bearing potential must have a negative baseline urine pregnancy test and agree to use a medically approved method of birth control for the duration of the study. All hormonal birth control must have been in use for a minimum of three months.
5. Healthy as determined by laboratory results, medical history, and physical exam by QI
6. Agrees to abstain from use of fermented foods or beverages with live bacteria or products containing active cultures for the duration of the study
7. Agrees to avoid alcoholic beverages and drugs containing alcohol during antibiotic treatment period and for at least one day after (days 0-8)
8. Agrees to avoid high caffeine intake (no more than 1 cup of coffee or 300 mg of caffeine/day) during antibiotic treatment period of the study (days 0-7)
9. Agrees to refrain from intake of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) during antibiotic treatment period of the study (days 0-7) and 72 hours prior to prior to lactulose and mannitol test
10. Agrees to refrain from using drugs and supplements containing aluminum, magnesium, sorbitol and/or mannitol 72 hours prior to lactulose and mannitol test.
11. Agrees to comply with all study procedures
12. Agrees to maintain current level of physical activity throughout the study

Exclusion Criteria

1. Women who are pregnant, breast feeding, or planning to become pregnant during the trial
2. Allergy or sensitivity to antibiotics (Ciprofloxacin, Metronidazole), Lactulose or Mannitol, or investigational product's active or inactive ingredients
3. Use of antibiotics or antifungals within three months prior to enrollment, including topical antibiotics or antifungals.
4. Clinically significant abnormal laboratory results at screening as assessed by the QI
5. Use of PPIs and H2-antagonists
6. Use of tobacco products
7. Type I or type II diabetes mellitus or treatment with anti-diabetic medication
8. Unstable metabolic diseases or chronic diseases as assessed by the QI
9. Self-reported current or pre-existing thyroid condition.
10. Unstable hypertension. Treatment on a stable dose of medication for at least 3 months will be considered by the QI
11. Current or history of any significant diseases of the gastrointestinal tract that may impact study outcomes as assessed by the QI
12. Significant cardiovascular event in the past 6 months. If the event occurred greater that 6 months ago and if on stable medication may be included after assessment by the QI on a case by case basis
13. Major surgery in the past 3 months or individuals who have planned surgery during the course of the trial. Participants with minor surgery will be considered on a case-by-case basis by the QI
14. Self-reported an autoimmune disease or an immune-compromised state
15. Self-reported HIV-, Hepatitis B- and/or C-positive diagnosis
16. History of or current diagnosis with kidney and/or liver diseases as assessed by the QI on a case-by-case basis, with the exception of history of kidney stones symptom free for 6 months
17. Self-reported medical or neuropsychological condition and/or cognitive impairment that, in the QI's opinion, could interfere with study participation
18. Self-reported blood/bleeding disorder. To be confirmed by the QI on a case by case basis
19. Cancer in the five years prior to enrollment, except skin cancers completely excised with no chemotherapy or radiation with a follow up that is negative. Volunteers with cancer in full remission for more than five years after diagnosis are acceptable following case by case assessment by QI.
20. Clinically significant illness in the four weeks prior to randomization
21. Current use of prescribed medications listed in Section 7.3.1
22. Current use of over-the-counter medications, supplements, foods and/or drinks listed in Section 7.3.2
23. Current use of any probiotic, prebiotic and symbiotic product unless willing to undergo a 4-week washout and abstain from consuming such products during the study.
24. Medical use of cannabinoid products
25. Use of any cannabinoid products (including synthetics) within one month of study entry
26. Alcohol or drug abuse within the last 12 months
27. High alcohol intake (\>2 per day or a total of \>10 standard drinks per week)
28. Blood donation 30 days prior to screening, during the study, or a planned donation within 30-days of the last study visit
29. Participation in other clinical research trials 30 days prior to screening
30. Any other active or unstable medical condition, that, in the opinion of the QI, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Seed Health

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gregor Reid, PhD

Role: PRINCIPAL_INVESTIGATOR

Lawson Health Research Institute, St. Joseph's Hospital

Locations

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KGK Science

London, Ontario, Canada

Site Status

Countries

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Canada

References

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Reference Type BACKGROUND
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De Wolfe TJ, Eggers S, Barker AK, Kates AE, Dill-McFarland KA, Suen G, Safdar N. Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection. PLoS One. 2018 Sep 28;13(9):e0204253. doi: 10.1371/journal.pone.0204253. eCollection 2018.

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Reference Type BACKGROUND
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Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013 Aug 2;341(6145):569-73. doi: 10.1126/science.1241165. Epub 2013 Jul 4.

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Ho L, Ono K, Tsuji M, Mazzola P, Singh R, Pasinetti GM. Protective roles of intestinal microbiota derived short chain fatty acids in Alzheimer's disease-type beta-amyloid neuropathological mechanisms. Expert Rev Neurother. 2018 Jan;18(1):83-90. doi: 10.1080/14737175.2018.1400909. Epub 2017 Nov 14.

Reference Type BACKGROUND
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Resta-Lenert S, Barrett KE. Probiotics and commensals reverse TNF-alpha- and IFN-gamma-induced dysfunction in human intestinal epithelial cells. Gastroenterology. 2006 Mar;130(3):731-46. doi: 10.1053/j.gastro.2005.12.015.

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van Baarlen P, Troost F, van der Meer C, Hooiveld G, Boekschoten M, Brummer RJ, Kleerebezem M. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways. Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1(Suppl 1):4562-9. doi: 10.1073/pnas.1000079107. Epub 2010 Sep 7.

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Suez J, Zmora N, Zilberman-Schapira G, Mor U, Dori-Bachash M, Bashiardes S, Zur M, Regev-Lehavi D, Ben-Zeev Brik R, Federici S, Horn M, Cohen Y, Moor AE, Zeevi D, Korem T, Kotler E, Harmelin A, Itzkovitz S, Maharshak N, Shibolet O, Pevsner-Fischer M, Shapiro H, Sharon I, Halpern Z, Segal E, Elinav E. Post-Antibiotic Gut Mucosal Microbiome Reconstitution Is Impaired by Probiotics and Improved by Autologous FMT. Cell. 2018 Sep 6;174(6):1406-1423.e16. doi: 10.1016/j.cell.2018.08.047.

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Spiller RC. Hidden Dangers of Antibiotic Use: Increased Gut Permeability Mediated by Increased Pancreatic Proteases Reaching the Colon. Cell Mol Gastroenterol Hepatol. 2018 Jul 11;6(3):347-348.e1. doi: 10.1016/j.jcmgh.2018.06.005. eCollection 2018. No abstract available.

Reference Type BACKGROUND
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Other Identifiers

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19SAHS

Identifier Type: -

Identifier Source: org_study_id

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