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

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ClinicalTrials.gov Identifier: NCT04171466
Recruitment Status : Recruiting
First Posted : November 21, 2019
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
Seed Health

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Antibiotic Side Effect Antibiotic-associated Diarrhea Antibiotic-induced Dysbiosis Antibiotic-induced Epithelial Barrier Disintegrity Other: Ciprofloxacin + Metronidazole Other: SH-DS01 Other: Placebo Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 64 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Determine the Efficacy of a Multi-strain Synbiotic (SH-DS01) to Restore Gut Barrier Integrity and Gut Microbiota Composition After Antibiotic Administration.
Actual Study Start Date : August 12, 2020
Estimated Primary Completion Date : May 31, 2021
Estimated Study Completion Date : June 1, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antibiotics

Arm Intervention/treatment
Active Comparator: Broad Spectrum Antibiotic Therapy + Microbial Consortia Other: 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.

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.

Placebo Comparator: Broad Spectrum Antibiotic Therapy + Placebo Other: 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.

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.

Active Comparator: No Antibiotic Therapy + Microbial Consortia 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.

Placebo Comparator: No Antibiotic Therapy + Placebo 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.




Primary Outcome Measures :
  1. Change in microbiota composition at 3 months as assessed by whole genome shotgun sequencing. [ Time Frame: Baseline- Days 91 ]
    Microbiota composition will be identified through fecal samples for total genomic DNA extraction in participants supplemented with SH-DS01 and with or without antibiotics.


Secondary Outcome Measures :
  1. Difference in serum LPS-binding protein (LBP) at Day 7. [ Time Frame: Baseline- Days 91 ]
    As a measure of intestinal barrier integrity in response to antibiotic therapy.

  2. Difference in the Intestinal Permeability Assessment (IPA) at Day 7 as measured by Lactulose/mannitol testing. [ Time Frame: Baseline- Days 91 ]
    As a measure of intestinal barrier integrity in response to antibiotic therapy.

  3. Metabolomic profile of stool samples. [ Time Frame: Baseline- Days 91 ]
    As assessed by untargeted metabolomics on whole stool samples.

  4. Number of participants with improved Antibiotic-Associated Gastrointestinal Function [ Time Frame: Baseline- Days 91 ]
    As assessed by daily symptom tracking software of stool quality, regularity, ease of expulsion, bloating, flatulence, and intestinal transit time.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04171466


Contacts
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Contact: Azza A Gadir, PhD 8446463586 azza@seed.com

Locations
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Canada, Ontario
KGK Science Recruiting
London, Ontario, Canada, N6A 5R8
Contact: Andrew Charrette         
Sponsors and Collaborators
Seed Health
Investigators
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Principal Investigator: Gregor Reid, PhD Lawson Health Research Institute, St. Joseph's Hospital
Publications:

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Responsible Party: Seed Health
ClinicalTrials.gov Identifier: NCT04171466    
Other Study ID Numbers: 19SAHS
First Posted: November 21, 2019    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: May 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Seed Health:
Gut microbiome
Dysbiosis
Antibiotic therapy
Rationally-defined consortia
Short-chain fatty acids
Gut metabolome
Metagenomic sequencing
Ciproflozacin
Metronidazole
Probiotic Therapy
Additional relevant MeSH terms:
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Diarrhea
Dysbiosis
Signs and Symptoms, Digestive
Pathologic Processes
Metronidazole
Ciprofloxacin
Anti-Infective Agents
Anti-Bacterial Agents
Antiprotozoal Agents
Antiparasitic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Cytochrome P-450 CYP1A2 Inhibitors
Cytochrome P-450 Enzyme Inhibitors