Clinical trial NCT03728868: Tolerability and Risk of Adverse Events With a Probiotic Supplement
Official title: Tolerability and Risk of Adverse Events With a Probiotic Supplement: A Randomised and Placebo Controlled Study in Healthy Individuals
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Individuals
Keywords: Faecalibacterium prausnitzii
Desulfovibrio piger
tolerability
blood glucose levels
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: MetaboGen AB
First posted: 2018-11-02
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: The butyrate-producing bacterium Faecalibacterium prausnitzii is abundant in the human bowel and can make up to 5% of the gastrointestinal flora in healthy individuals. A reduced presence of it has been associated with an imbalance in the gastrointestinal flora of metabolic syndromes such as type 2 diabetes, fat liver, and in inflammatory bowel disease.

The present double-blind, placebo-controlled, randomized study is designed to investigate if dietary supplementation with F.prausnitzii (combined with D. piger) once a day for 8 consecutive weeks is tolerated compared to placebo and if it can affect the metabolism in a positive way.

Detailed description: The understanding of the role of the gastrointestinal microbes for human health has gained considerable interest in recent years. The butyrate-producing bacterium Faecalibacterium prausnitzii is a naturally occurring bacterial species in the human gut that can make up to 5% of the gastrointestinal flora in healthy individuals.

Several studies have shown that the presence of butyrate producing bacteria, including F. prausnitzii, is lower in patients with inflammatory bowel disease; Crohn's disease and ulcerative colitis. Furthermore, lower levels of short fatty acids have been found in people with ulcerative colitis as compared to healthy individuals. Similar results have been obtained from studies about Crohn's disease, where people with a low abundance of F. prausnitzii run a higher risk of post-operative recurrence of their disease.

It has become evident that bacteria in the human gastrointestinal tract are symbiotic and dependent on each other's metabolism. Studies conducted by the sponsor (Metabogen AB) have shown that butyrate production from F. prausnitzii increases in the presence of Desulfovibrio piger, a common sulphate-reducing bacterium present in the human intestine. The symbiotic relationship between F. prausnitzii and D. piger can be utilised by combining these bacterial species into a probiotic dietary supplement, thus maintaining butyrate production in the intestine.

In animal models, who received approximately 5,000 times higher doses per kilogram of body weight than the highest dose scheduled in the proposed study, the intake of F. prausnitzii has shown anti-inflammatory effects as well as positive effects on the metabolism.

The present study is a double-blind, placebo-controlled, randomized, study in 48 healthy individuals (men and women) between 20 and 40 years old recruited from the general population. These volunteers will either receive F. prausnitzii and D. piger (in two different doses) or placebo orally once a day for 8 consecutive weeks. The investigators will assess how well treatment with the study product compared to placebo is tolerated (termination due to adverse events within 8 weeks of treatment) and if it can cause gastrointestinal symptoms (measured with The Gastrointestinal Symptom Rating Scale). The investigators will also assess if the intake of the study product can potentially give positive effects in the metabolism (blood glucose, fatty acids, protein ect).

Eligibility criteria: Inclusion Criteria:

1. 20 to 40 years old
2. Signed consent for participation
3. Healthy individuals without any known diseases
4. Willingness and ability to attend to planned visits, participate in telephone interviews and follow study instructions
5. Understanding the Swedish language in spoken and written terms

Exclusion Criteria:

1. Ongoing treatment with prescription drugs
2. Regular or sporadic intake of probiotic products (foods with probiotics are allowed)
3. Treated with antibiotics during the last 3 months
4. Pregnancy
5. Have experienced gastrointestinal tract symptoms (during the last month), which could affect study participation, as deemed by study physician.
6. Current tobacco use (smoking or snuff)
7. Participation in another clinical study

Primary outcomes:
measure: Tolerability of the oral intake of F. prausnitzii and D. piger, defined as study discontinuation due to adverse events under 8 weeks of treatment.
timeFrame: 0-8 weeks
Secondary outcomes:
measure: Gastrointestinal side effects, measured using the Gastrointestinal Symptom Rating Scale (GSRS)
timeFrame: 0-8 weeks
measure: Effects on inflammation - erythrocyte sedimentation rate (safety parameters )
timeFrame: 0-8 weeks
measure: Effects on inflammation - CRP (safety parameters )
timeFrame: 0-8 weeks
measure: Effect on hematopoiesis - red blood cells (safety parameters)
timeFrame: 0-8 weeks
measure: Effect on hematopoiesis - white blood cells (safety parameters)
timeFrame: 0-8 weeks
measure: Effect on hematopoiesis - platelets (safety parameters)
timeFrame: 0-8 weeks
measure: Effects on liver enzymes - ALAT (safety parameters)
timeFrame: 0-8 weeks
measure: Effects on liver enzymes - ASAT (safety parameters)
timeFrame: 0-8 weeks
measure: Effects on liver enzymes - ALP (safety parameters)
timeFrame: 0-8 weeks
measure: Effects on serum bilirubin (safety parameters)
timeFrame: 0-8 weeks
measure: Effects on the blood glucose
timeFrame: 0-8 weeks
measure: Effects on abundance of short-chain fatty acids
timeFrame: 0-10 weeks
measure: Colonization with F. prausnitzii
timeFrame: 0-8 weeks
measure: Effect on renal function(safety parameter)
timeFrame: 0-8 weeks
measure: Effect on serum total protein (safety parameter)
timeFrame: 0-8 weeks
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Geriatric Medicine, Sahlgrenska University Hospital, Mölndal
state: Västra Götaland
Study officials:
affiliation: Dept Geriatrics, Sahlgrenska University Hospital
name: Mattias Lorenzon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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