Autoflor -Lyophilized Capsulated Autological FMT to Restore Gut Microbiome After Treatment With Antibiotics (FMT)

February 13, 2024 updated by: Otto Helve

Lyophilized Capsulated Autological Fecal Microbial Transplant to Restore Gut Microbiome After Treatment With Antibiotics

In this clinical trial, our aim is to assess the effect of auto-FMT (Fecal microbiome transplantation) on the intestinal microbiota, after a course of antibiotics.

30 healthy adults are recruited. All are given a five day course of amoxicillin-clavulanate. The subjects are double blinded and randomized to two groups. Group A is given autologous FMT (auto-FMT) on day 7 (two days after the end of the course of antibiotics) and Group B is given auto-FMT on day 28 (23 days after the end of the course of antibiotics).

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The use of antibiotics also has short- and long-term disadvantages for the individual. In trials with human adults, oral intake of antibiotics has been shown to markedly affect the intestinal microbiota, by reducing the diversity and altering the composition, as well as by spreading of antibiotic resistance genes (AR).

Freeze dried FMT products have long lasting stability of fecal microbiota useful for encapsulation. The amount of capsules needed to digest is also much lower compared to using fresh or frozen material.

Anticipating a 25% drop-out we will recruit 40 healthy adults between 18-40 years of age. Inflammation status of the participants at recruitment will be tested by taking blood samples. A 100-150g sample of the participants feces is obtained. The feces will be tested for potential harmful pathogens.

50g of collected stool is processed within 6 h of passage, diluted in 0.85% NaCl, homogenized using a mixer. The fecal suspension is filtered through sterilized metal sieves under biological safety cabinet. The suspension is then centrifuged. Supernatant is then decanted into new centrifuge tubes and centrifuged. The upper bacterial pellet is resuspended in isotonic sodium chloride with 10% trehalose. The suspension is stored at -80°C up to two weeks before being lyophilized. The solution is lyophilized in a Lyoquest plus Ae85C (Telstar, Tarrasa, Spain) for 44 h, and the resulting product is encapsulated in hypromellose capsules (sizes 0, Capsugel Enprotect, Cambridge, MA, USA) and stored at 4°C. The protocol is applied from previous studies with capsulated FMT. Each capsule contains approximately 0.35g lyophilized stool extract. O'boy hot chocolate powder is used as placebo.

The 30 participants are randomized and double blinded into two groups, each having 15 subjects. All participants will be given a 5-day (Day 1-5) course of Amoxicillin + Clavulanate 875/125 mg × 2.

Group A Intervention group. The participants will be given 4 capsules containing fecal matter (Capsule 1) after treatment with antibiotics on day 7.

Group B Control group. The participants will be given 4 placebo capsules (Capsule 2) after treatment with antibiotics on day 7.

Group B will be given FMT capsules (Capsules 1) as "rescue therapy" on day 28. Group A will be given placebo (Capsules 2) as described earlier.

The capsules (at timepoints 7 and 28 days) are administered under the supervision of the research team. The capsules are swallowed with juice. Participants are asked to be on a clear liquid diet for 8 h prior to the intervention. No solid food should be taken within two hours of digesting the capsules. Otherwise, no restrictions to the diet are considered necessary. During the visit the participants are interviewed and ensured that no signs of infection have occurred and that there have been no significant changes in bowel function.

Fecal samples will be collected from all participants weekly starting from day 6 for 7 weeks until day 48 (total 7 samples (3 vials/sample)). The study samples are stored in stool collection containers in the home freezer (-18°C) until collected by the study personnel and stored there after at -80°C. Calprotectin samples are stored in the refrigerator until collected by the study personnel.

The participants will fill in a questionnaire including questions of any abdominal symptoms, defecation frequency, stool consistence, abdominal pain, nausea and other used medication weekly until 7 weeks. Use of additional antibiotics during the follow-up period leads to drop-out. Participants complete a quality of life (HRQoL) survey at day 1 (the introduction of antibiotics), on day 7 when auto-FMT/placebo (first intervention) is performed, on day 28 (second intervention) and at the end of the follow-up period (day 48) (http://www.15d-instrument.net/15d/).

Participants with fever, watery diarrhea (> 3 loose stools in 24 hours), bloody stools, abdominal pain and cramping) are tested for C. difficile. In case of fever, the CRP level and complete blood count are controlled. Participants with bloody stools will be excluded from the study.

Blood samples will be taken on days 7, 9, 28 and 30. 5mL of blood is gathered (C-reactive protein, complete blood count, plasma).

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Finland
    • Uusimaa
      • Helsinki, Uusimaa, Finland
        • Helsinki University Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Kaija-Leena Kolho, Professor
        • Sub-Investigator:
          • Otto Helve, Docent

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

-previously healthy

Exclusion Criteria:

  • IBD (inflammatory bowel disease)
  • celiac disease
  • abdominal symptoms such as diarrhea or constipation necessitating medical therapy
  • pregnancy and breastfeeding
  • allergy towards antibiotics penicillins
  • allergy towards soya.
  • trehalose intolerance.
  • travelling outside of European Union during the last 3 months
  • use of antibiotics during the last 3 months
  • use of probiotics during the previous 2 weeks or during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
The participants will be given 4 capsules containing fecal matter (Capsule 1) after treatment with antibiotics on day 7. Intervention group will be given placebo (Capsules 2) on day 28.
Other: FMT
Capsulated oral auto fecal microbiota transplant
Other: Placebo
Capsulated hot chocolate powder
Drug: Amox Clav
5 day course of Amoxicillin Clavulanic acid given to all participants
Other Names:
  • Amorion comp
Placebo Comparator: Control

The participants will be given 4 placebo capsules (Capsule 2) after treatment with antibiotics on day 7.

Control group will be given FMT capsules (Capsules 1) as "rescue therapy" on day 28.
Other: FMT
Capsulated oral auto fecal microbiota transplant
Other: Placebo
Capsulated hot chocolate powder
Drug: Amox Clav
5 day course of Amoxicillin Clavulanic acid given to all participants
Other Names:
  • Amorion comp

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Feasibility and safety; Number of participants with treatment-related adverse events such as; nausea, vomiting, signs of infection such as elevation of CRP after receiving the capsules, bloody stools
Time Frame: 2 months
The feasibility and safety of the transplantation process using lyophilized auto-FMT. All adverse events are reported, CRP is taken from all patients at the day of the transplant and 2 day after. The participants answer to weekly online questionaires including questions of any abdominal symptoms, defecation frequency, stool consistence, abdominal pain, nausea and other used medication weekly until 7 weeks.
2 months
Taxonomic restoration of the gut microbiome at day 27.
Time Frame: 1 month
Quantitative PCR will be used for quantitative microbiota profiling.
1 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Magnitude and duration of GI-symptoms
Time Frame: 3 months
The investigators will use questionaires filled by the participants.
3 months
Impact of FMT given to placebo group on day 28 on gut microbiome on day 48
Time Frame: 3 months
Quantitative PCR will be used for quantitative microbiota profiling.
3 months
The percentage of participants with restoration of intestinal microbiome.
Time Frame: 3 months
The investigators observe especially the influence of auto-FMT towards successful restoration of bacteria from beneficial groups, including Lachnospiraceae (family), Ruminococcaceae (family), and Bacteroidetes (phylum).
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otto Helve

Collaborators

University of Helsinki

Investigators

  • Study Director: Otto Helve, Docent, University of Helsinki

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2024

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

January 18, 2024

First Submitted That Met QC Criteria

January 31, 2024

First Posted (Actual)

February 9, 2024

Study Record Updates

Last Update Posted (Actual)

February 14, 2024

Last Update Submitted That Met QC Criteria

February 13, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUS/2231/2023

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

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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