Healthy Stool Volunteer Donors for Fecal Microbiota Transplantation Trials

Overview

Currently, ANSM recommendations govern FMT (Fecal Microbiota Transplantation) in clinical trials. The collection and validation of these stool donations as part of the trials is complex and not very efficient. It therefore seems essential to identify the limiting factors and the characteristics of Healthy Volunteer Donors to optimize the number of valid stool donations.

Detailed description

If the ANSM recommendations govern FMT (Fecal Microbiota Transplantation) in clinical trials, the selection, inclusion of Healthy Volunteer Donors (HVD), then the collection and validation of these stool donations is complex and not very effective. It therefore seems essential to identify the limiting factors and the characteristics of HVD to optimize the number of valid stool donations.

Healthy voluntary donors of stools for the preparation of TMF (Healthy Volunteer Donors, -TMF) for trials to evaluate its effectiveness in various pathologies will be selected, included and followed in a common protocol (ANSM agreement obtained) in order to facilitate this entire process and pool resources. This will allow us to describe the clinical characteristics and lifestyle habits of Healthy Volunteer Donors associated with the validity of stool donations.

Interventions

• Other Stools donation
  Healthy volunteer donors included in the selection process to donate stool for the preparation of a TMF as part of research projects. Donors will be followed from their selection until 6 months after their last valid stool donation.

Primary outcome measures

• Proportion of HVD included who made at least 1 valid stool donation in the 12 months following their inclusion [Time frame: 12 months]

Secondary outcome measures (9)

• Proportion of "good donors": included donors having made at least 5 valid stool donations in the 12 months following their inclusion. [Time frame: 12 months]
• Description of the clinical characteristics of HVD performing stool donation [Time frame: 12 months]
• Description of the lifestyle habits of HVD performing stool donation [Time frame: 12 months]
• Reasons for non-eligibility during the inclusion visit or during the phone screening [Time frame: 5 years]
• Factors limiting the number of donations made by HVD per donation period of 28 days maximum [Time frame: 12 months]
• Evaluate the membership of participation of HVD [Time frame: 5 years]
• Evaluate the duration of participation of HVD [Time frame: 5 years]
• Reasons for premature termination or non-validation of stools [Time frame: 5 years]
• Assess the characteristics of the microbiota of valid donations [Time frame: 5 years]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years and < 50 years
• 17 kg/m² < body mass index < 30 kg/m²
• Regular bowel movement defined as at least 1 stool every other day and maximum 2 stools per day
• Subject with health insurance (AME excepted)
• Informed written consent

Exclusion criteria

Definitive non-inclusion criteria:

• Infectious risk :

\- Known HIV, HBV, HCV, HTLV infection

• Residence of more than 2 years in the intertropics zone within the previous 5 years
• Hospitalization abroad for more than 24 hours in the last 12 months (including a member of the healthy volunteers donor's entourage)
• Risk factors for Creutzfeldt-Jakob disease (history: treatment with extractive growth hormone, a family case of transmissible spongiform subacute encephalopathy, surgery with opening of the dura or neurosurgery or invasive brain exploration before 1 January 1995, stay in United Kingdom for a duration greater than 1 year cumulatively between 1980 and 1996 or the presence of neurological or neuropsychiatric scalable recent clinical signs)
• Previous history of typhoid fever, tuberculosis and malaria
• Past or current injection drug user or regular use of other drug
• Gastrointestinal disease:

\- Personal or 1st degree family history of: inflammatory bowel disease or celiac disease

• Personal history of irritable bowel syndrome
• Previous history of gastrointestinal neoplasia or polyps
• Family history of 1st degree gastrointestinal neoplasia or polyps before age 60
• 1st degree family history of one of the following autoimmune or inflammatory disease : inflammatory arthritis, psoriasis, multiple sclerosis, type I diabetes, spondylitis, lupus and Basedow disease

\- If family history unknown in the first degree, the donor is not eligible

• Previous history of :

• Subject prone to hemorrhoids (at least 1 event within the previous 1 year)
• Subject with an active chronic illness (except active chronic mild allergic disease o (example: allergic rhinitis, chronic eczema…)) o Diagnosis of Gilbert's syndrome done by screening is not a chronic disease. The healthy volunteer donor will therefore remain eligible.
• Serious allergy requiring hospitalization within the previous 12 months
• Curative long-term treatment
• Severe allergy requiring hospitalization in the last 12 months
• Allogeneic human or animal tissue or organ transplant
• Factors that may affect the composition of the intestinal microbiota:

\- Special Diet (example: gluten-free...)

• Lactose-free, vegetarian and vegan diets are permitted.
• Pregnancy or breastfeeding
• Taking immunosuppressants (eg calcineurin inhibitors, corticosteroids, biological agents, etc.)
• Antineoplastic chemotherapy
• Subject under legal protection
• Participation in any other interventional study except studies for stool donation

Temporary non-inclusion criteria

• Infectious risk :

\- Unprotected sexual intercourse with a new partner in the previous 4 months and/or sexual intercourse with several different persons within the previous 4 months

\- sexual partner who has had more than 1 partner within the previous 4 months and/or

\- sexual transmitted infection within the previous 4 months (healthy volunteer donor himself or sexual partner)

\- Sexual relationship in exchange for money or drugs in the last 12 months. (healthy volunteer donor himself or sexual partner)

\- Sexual relationship with a partner with positive serology for HIV, viral hepatitis B or C, in the last 6 months.

\- Sexual relationship with a partner who has used intravenous drugs, doping substances

\- Hospitalization abroad for more than 24 hours in the last 12 months (healthy volunteer or entourage)

\- Travelling within the previous 6 months except : Germany, Austria, Belgium, Spain, Finland, Ireland, Italia, Luxembourg, Netherland, Portugal, Greece, Slovenia, Cyprus, Malta, Slovakia, Estonia , Bulgaria, Croatia , Hungary, Latvia , Lithuania, Poland , Romania, Czech Republic, the United Kingdom, Denmark, Norway, Sweden, Switzerland, USA, Iceland, Australia New Zealand, Japan, South Korea, Singapore, Israel or Canada.

\- Blood transfusion, piercing (including earrings) or tattoo within the previous 4 months

\- Surgery (all types) or hospitalization within the previous 4 months

\- Person living under the same roof or sexual partner with an infectious or contagious disease (i.e who have been hospitalized) within the previous 4 months

\- Blood exposure accident (for wound, pricking or projection ...) within the previous 4 months

\- Dental care within the previous 7 days

\- Gastroenteritis within the previous 3 months (defined by acute onset of diarrhea (> 3 soft or liquid stools per day) and duration < one week)

\- Episode of infection or skin infection/lesion within the previous 15 days 2-Risk linked to Covid-19

\- Confirmed infection in the previous 28 days (after symptoms have ceased)

• Clinical signs of suspected infection (chill, cough, fever, dyspnea, myalgia, asthenia, malaise, pharyngeal pain, anosmia , ageusia, rhinorrhea, chest pain, headache, diarrhea) in the previous 28 days (after the end of symptoms)
• Having been in risky contact (according to the definition of Santé Publique France with a person whose infection is confirmed or suspected: "14 days after the last risky contact: if the recommended screening tests in the event of risky contact between D15-D28 are negative "In the 28 days preceding inclusion in the absence of a screening test. Healthcare professionals using recommended protective measures with COVID patients are not considered high-risk contacts 3- Monkeypox risk
• Confirmed or suspected infection within the previous 42 days ( after beginning of symptoms)
• Risky contact with a person with confirmed or suspected infection within the previous 21 days (from the date of last contact)

4- vaccination with a live attenuated vaccine during the last month 5- Chronic diarrhoea in the previous 3 months or chronic constipation (fewer than 3 bowel movements per week for more than 6 months) 6- Excessive alcohol consumption in the last 4 months. (French Public Health definition: 10 standard drinks per week and a maximum of 2 drinks per day)

7 - Factors that may affect the composition of the intestinal microbiota:

• Taking antibiotic or antifungal (oral) in the previous 3 months before donation
• Taking non-steroidal anti-inflammatory drugs (oral) in the previous month before donation
• Taking corticosteroids (oral) in the previous 4 weeks before donation. Corticosteroids allowed if taken more than 4 weeks before donation. and not for an autoimmune or inflammatory disease.

Temporary or permanent exclusion criteria:

\- At each visit of the donation period, the temporary or definitive exclusion criteria (identical to the temporary or definitive non-inclusion criteria) will be rechecked

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Other

Study locations

France · 1 center

• LRIPH CRC-Est SAT — Paris

Identifiers

NCT: NCT06478823 · APHP220606 · 2022-A01401-42

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗