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

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.

Patrocinadores

Patrocinador principal: Seed Health

Fuente Seed Health
Resumen breve

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.

Estado general Not yet recruiting
Fecha de inicio June 1, 2020
Fecha de Terminación January 1, 2021
Fecha de finalización primaria July 31, 2020
Fase N/A
Tipo de estudio Interventional
Resultado primario
Medida Periodo de tiempo
Change in microbiota composition at 3 months as assessed by whole genome shotgun sequencing. Baseline- Days 91
Resultado secundario
Medida Periodo de tiempo
Difference in serum LPS-binding protein (LBP) at Day 7. Baseline- Days 91
Difference in the Intestinal Permeability Assessment (IPA) at Day 7 as measured by Lactulose/mannitol testing. Baseline- Days 91
Metabolomic profile of stool samples. Baseline- Days 91
Number of participants with improved Antibiotic-Associated Gastrointestinal Function Baseline- Days 91
Inscripción 64
Condición
Intervención

Tipo de intervención: Other

Nombre de intervención: Ciprofloxacin + Metronidazole

Descripción: 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.

Tipo de intervención: Other

Nombre de intervención: SH-DS01

Descripción: 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.

Tipo de intervención: Other

Nombre de intervención: Placebo

Descripción: 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.

Elegibilidad

Criterios:

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

Género: All

Edad mínima: 18 Years

Edad máxima: 55 Years

Voluntarios Saludables: Accepts Healthy Volunteers

Oficial general
Apellido Papel Afiliación
Gregor Reid, PhD Principal Investigator Lawson Health Research Institute, St. Joseph's Hospital
Contacto general

Apellido: Azza A Gadir, PhD

Teléfono: 8446463586

Email: [email protected]

Ubicación
Instalaciones: Contacto: KGK Science Andrew Charrette
Ubicacion Paises

Canada

Fecha de verificación

May 2020

Fiesta responsable

Tipo: Sponsor

Palabras clave
Tiene acceso ampliado No
Condición Examinar
Número de brazos 4
Grupo de brazo

Etiqueta: Broad Spectrum Antibiotic Therapy + Microbial Consortia

Tipo: Active Comparator

Etiqueta: Broad Spectrum Antibiotic Therapy + Placebo

Tipo: Placebo Comparator

Etiqueta: No Antibiotic Therapy + Microbial Consortia

Tipo: Active Comparator

Etiqueta: No Antibiotic Therapy + Placebo

Tipo: Placebo Comparator

Información de diseño del estudio

Asignación: Randomized

Modelo de intervención: Parallel Assignment

Propósito primario: Prevention

Enmascaramiento: Double (Participant, Care Provider)

Fuente: ClinicalTrials.gov