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

Microbial Colonization Clinical Trial

— FMT  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06250413
• Other study ID #: HUS/2231/2023
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 2024
• Est. completion date: December 2027

Study information

• Verified date: February 2024
• Source: Helsinki University Central Hospital
• Contact: Noora Carpén, MD
• Phone: +358 9 4711
• Email: noora.carpen[@]hus.fi
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: December 2027
• Est. primary completion date: December 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

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.

Related Conditions & MeSH terms

• Antibiotic Side Effect
• Communicable Diseases
• Infections
• Microbial Colonization

Intervention

Other:
• FMT
Capsulated oral auto fecal microbiota transplant
• Placebo
Capsulated hot chocolate powder

Drug:
• Amox Clav
5 day course of Amoxicillin Clavulanic acid given to all participants

Locations

Country	Name	City	State
Finland	Helsinki University Hospital	Helsinki	Uusimaa

Sponsors (2)

Lead Sponsor	Collaborator
Otto Helve	University of Helsinki

Country where clinical trial is conducted

Finland, 

References & Publications (5)

Bulow C, Langdon A, Hink T, Wallace M, Reske KA, Patel S, Sun X, Seiler S, Jones S, Kwon JH, Burnham CA, Dantas G, Dubberke ER. Impact of Amoxicillin-Clavulanate followed by Autologous Fecal Microbiota Transplantation on Fecal Microbiome Structure and Met — View Citation

Jernberg C, Lofmark S, Edlund C, Jansson JK. Long-term impacts of antibiotic exposure on the human intestinal microbiota. Microbiology (Reading). 2010 Nov;156(Pt 11):3216-3223. doi: 10.1099/mic.0.040618-0. Epub 2010 Aug 12. — View Citation

Reygner J, Charrueau C, Delannoy J, Mayeur C, Robert V, Cuinat C, Meylheuc T, Mauras A, Augustin J, Nicolis I, Modoux M, Joly F, Waligora-Dupriet AJ, Thomas M, Kapel N. Freeze-dried fecal samples are biologically active after long-lasting storage and suited to fecal microbiota transplantation in a preclinical murine model of Clostridioides difficile infection. Gut Microbes. 2020 Sep 2;11(5):1405-1422. doi: 10.1080/19490976.2020.1759489. Epub 2020 Jun 5. — View Citation

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, Shap — View Citation

Taur Y, Coyte K, Schluter J, Robilotti E, Figueroa C, Gjonbalaj M, Littmann ER, Ling L, Miller L, Gyaltshen Y, Fontana E, Morjaria S, Gyurkocza B, Perales MA, Castro-Malaspina H, Tamari R, Ponce D, Koehne G, Barker J, Jakubowski A, Papadopoulos E, Dahi P, — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Primary	Taxonomic restoration of the gut microbiome at day 27.	Quantitative PCR will be used for quantitative microbiota profiling.	1 month
Secondary	The percentage of participants with restoration of intestinal microbiome.	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
Secondary	Magnitude and duration of GI-symptoms	The investigators will use questionaires filled by the participants.	3 months
Secondary	Impact of FMT given to placebo group on day 28 on gut microbiome on day 48	Quantitative PCR will be used for quantitative microbiota profiling.	3 months