Revisions for Safety evaluation of Bacillus coagulans AO1167 for its use as a probiotic in humans | Registro Público Cubano de Ensayos Clínicos

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Current revision:

Safety evaluation of Bacillus coagulans AO1167 for its use as a probiotic in humans

General information

Section to complete general information about the trial: scientific and public title, protocol identifiers, sponsors and Source(s) of Monetary or Material Support.

Scientific title:

Safety evaluation of Bacillus coagulans AO1167 for its use as a probiotic in humans

Secondary indentifying numbers:

Not applicable

Issuing authority of the secondary identifying numbers:

Not apllicable

Source(s) of monetary or material support:

The Biocollective LLC Company, Denver Colorado USA,

Authorization for beginning

Section to complete information about the regulatory approval of clinical trial: regulatory agency name, approval date and reference number in the agency.

Regulatory instance to authorize the initiation of the study:

Only approved by Ethics Committees

Principal investigator

Section to complete information about Email address, telephone number and postal address of the Principal Investigator.

First name:

Gissel

Last name:

García Menéndez

Medical Specialty :

Graduate in Biochemistry, Master in Virology, PhD in Health Science

Affiliation:

Hermanos Ameijeiras Clinical Surgical Hospital

Postal address:

San Lazaro 701 croner to Belascoain

City:

Havana

Country:

Cuba

Zip Code:

10300

Telephone:

+53-78761632

Email address:

gisselgarcia@infomed.sld.cu

gisselgarcia2805@gmail.com

Clinical sites to participate

Section to complete the data related to the clinical sites involved in the trial: site and responsible investigator for every site.

Countries of recruitment:

Cuba

Clinical sites:

Not applicable

Recruitment status

Section to complete information about the recruitment status and the date of first enrolment subject

Recruitment status:

Complete

Date of first enrollment:

05/09/2023

Health condition and Intervention

Section to complete information about the primary medical condition(s) or problem(s) studied and, a characteristics of the intervention(s).

Health condition(s) or Problem(s) studied:

healthy volunteers

Health condition(s) code:

Healthy Volunteers

Healthy Aging

Intervention(s):

Group I (Experimental) One capsule of Bacillus coagulans AO1167 (2.5 x109 bacteria / capsule mixed with the following excipients: calcium phosphate, magnesium stearate and colloidal silica), orally, fasting for 2 months . Group II (Control) Placebo; same appearance and application scheme as the Experimental product.

Intervention code:

Probiotics

Dietary Supplements

Placebos

Intervention keyword:

Bacillus coagulans AO1167

Outcomes and Timepoint

Section to complete information about primary and secondary outcomes including. It includes the metric or method of measurement used and, the time point for every outcome.

Primary outcome(s):

1.- Adverse effect. It will be measured taking into account: the presence of the adverse effect: (It does not appear to be an adverse effect, Possible adverse effect, Similar to an adverse effect, Adverse effect). Measurement time: at the end of the study, day 60. 2.- Intensity of the Adverse Effect. (Mild (Does not produce restrictions in daily activities), Moderate (Produces a partial restriction of daily activities), Severe (Inability to carry out daily activities)). Measurement time: at the end of the study, day 60.

Key secondary outcomes:

Hematological variables, clinical chemistry, hemodynamic parameters and calculation of muscle mass Clinical Chemistry: -Liver enzymes (UKAT/L) -creatinine (umolL/L) -Urea (mmol/L) Hematological parameters Blood glucose (mmol/L), Leukocytes (x 109/L) Red blood cells (x 1012/L) Hemoglobin (g/dL) Hematocrit (%) MCV (fL) MCHC (g/dL) RDW (%) platelets (x 109/L) MPV (fL) Neutrophils (%) Lymphocytes (%) Monocytes (%) Eosinophils (%) Basophils (%) Neutrophils (x 109/L) Lymphocytes (x 109/L) Monocytes (x 109/L) Eosinpophils (x 109/L) Basophils (x 109/L) Hemodynamic Parameters Systolic blood pressure (mmHg). Diastolic blood pressure (mmHg) Heart rate (bpm) Calculation of muscle mass Muscle mass (MM) will be calculated for men and women using the following formulas using height and weight. For Men: MM=(0.32810*Weight)+(0.33929*height)-29.5336 For Women: MM=(0.29569*weight)+(0.41813*height)-43.2933 Measurement time: All the variables will be measured at the beginning, day 0; and at the end of the study, day 60.

Selection criterias

Section to complete information about the inclusion and exclusion criteria for participant selection, including age and gender.

Gender:

Male/Female

Minimum age:

19 years

Maximum age:

none

Inclusion criteria:

1.- Healthy individuals, over 18 years of age and will have no distinction of sex or skin color. 2.- They give their consent to participate in the study. 3.- Individuals who have hematological, clinical chemistry and hemodynamic parameters in normal ranges

Exclusion criteria:

Individuals suffering from any comorbidity and who show alterations in their hematological, clinical or hemodynamic parameters

Type of population:

Adults

Type of participant:

Healthy volunteers

Study design

Section to complete information about the characteristics of the study design.

Type study:

Interventional

Purpose:

Other

Other purpose:

This is a study that will evaluate the probiotic strain Bacillus coagulans AO1167 in healthy individuals, which has anti-inflammatory properties, so its use will have an impact on intestinal health as well as on improving the immunity of individuals.

Allocation:

Randomized controlled trial

Masking:

Double Blind

Control group:

Placebo

Study design:

Parallel

Phase:

1

Target sample size:

100

Contact for public queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to general queries, including information about current recruitment status

First Name:

Gissel

Last Name:

Garcia Menendez

Specialty:

Graduate in Biochemistry, Master in Virology, PhD in Health Science

Affiliation:

Hermanos Ameijeiras Clinical Surgical Hospital

Postal Address:

San Lazaro 701 esq. to Belascoain

City:

Havana

Country:

Cuba

Zip Code:

10300

Telephone:

+53-78761632

Email :

gisselgarcia@infomed.sld.cu

gisselgarcia2805@gmail.com

Contact for scientific queries

Section to complete information about Email address, telephone number and postal address of the contact who will respond to scientific queries.

First Name:

Gissel

Last Name:

Garcia Menendez

Specialty:

Graduate in Biochemistry, Master in Virology, PhD in Health Science

Affiliation:

Hermanos Ameijeiras Clinical Surgical Hospital

Postal Address:

San Lázaro 701 esq. to Belascoain

City:

Havana

Country:

Cuba

Zip Code:

10300

Telephone:

+53-78761632

Email :

gisselgarcia@infomed.sld.cu

gisselgarcia2805@gmail.com

Research Ethics Committees

Section to complete the data related to the review ethics committees.

Name of Research Ethics Committees:

Hermanos Ameijieras Clinical Surgery Hospital

Status of evaluation:

Approved

Status of evaluation date of Ethic Committee:

15/02/2023

Postal address of Ethic Committee :

San Lazaro 701 corner Belascoain, ZC 10300, Cuba

Telephone:

+53-78761000

Email:

hha@infomed.sld.cu

About study completion

Section to complete the data related to the study completion.

Final enrolment number:

100

Study completion date:

03/12/2023

Results Study

Section to complete the data related to the summarized results.

Participant flow:

A total of 254 accepted for eligibility, 54 were excluded and 100 healthy volunteers were randomly allocated to either the H. coagulans AO1167B or Placebo groups, with 50 individuals in each group. We lost to follow -up ,1 participants for personal reasons in the Placebo cohort

Baseline characteristics:

Distribution of cases according to demographics parameters Demographic Variables H. coagulans AO1167B cohort (n=50) Placebo cohort (n=49) pValue No % No % Sex Female 31 62 31 63.3 0.896 a Male 19 38 18 36.7 Age (years) Median ± SD 42.82±16.3 44.43 ± 14.74 1.0 b BMI Median ± SD 23.20 ± 3.93 23.63± 4.17 0.764a

Outcome measures:

Primary Outcome Most participants (86.9%, n=86) did not experience any AEs (Table 6). Among them, 80% were in the probiotic group (n=40) and 93.9% were in the placebo group (n=46). There was a significant difference in the incidence of AEs between the treated and placebo groups (p = 0.04). Secondary Outcome: The analysis of independent samples showed at baseline, only cholesterol levels were statistically significant (p = 0.020). By day 60, significant changes were observed in albumin (p < 0.01), total triglycerides (p = 0.031), and total bilirubin (p = 0.028) in both study groups. Significant differences were found at both baseline (ALAT p = 0.008, ASAT p < 0.01) and day 60 (ALAT p = 0.047, ASAT p < 0.01). In the H. coagulans group, a student’s T-test for related samples showed significant decreases in creatinine (p = 0.032), albumin (p < 0.01), and MVC (p = 0.003). Significant increases were found in ASAT (p < 0.01), triglycerides (p = 0.001), total bilirubin (p = 0.010), MCHC (p < 0.01), and MPV (p = 0.040). In the placebo group, significant increases were detected in urea (p = 0.012), GGT (p = 0.026), HTC (p = 0.001), and MVC (p < 0.01). Significant reductions were found in ALAT (p = 0.002), ASAT (p < 0.01), cholesterol (p < 0.01), total bilirubin (p = 0.002), and direct bilirubin (p = 0.001). Bioimpedance measurements of weight and BMI showed no significant differences between study groups when analysed using the T-test for independent and related samples. SF-36 questions (1, 6, 7, 11) on physical and emotional health status were analysed. Responses in both groups showed highly similar behaviours over time (Kappa ~1, p = 0.000), indicating strong agreement between initial and subsequent responses in both groups

Adverse events:

Most participants (86.9%, n=86) did not experience any AEs (Table 6). Among them, 80% were in the probiotic group (n=40) and 93.9% were in the placebo group (n=46). There was a significant difference in the incidence of AEs between the treated and placebo groups (p = 0.04). Three AE cases occurred in the Placebo group: two reported looser stools, and the third, oedema, coincided with a new dengue infection, likely linked to the virus. Among those taking H. coagulans probiotic capsules, 10 individuals (20%) experienced mild AE. These included gastrointestinal pain or discomfort (n=2), gas (n=5), headache (n=1), and constipation (n=2). The study comprised 62 females and 37 males. Most AE cases were reported by females (10/62) compared to males (3/37). One female (7%) from the Placebo group experienced moderate intensity AE coinciding with a dengue infection debut; others reported mild effects that lessened over treatment days without hindering daily activities.

Summary study:

Heyndrickxia coagulans, a lactic acid-producing bacterium, exhibits characteristics of both Lactobacillus and Bacillus genera. Clinical evidence suggests that Heyndrickxia coagulans strains have significant health benefits. This study aims to assess the safety of Heyndrickxia coagulans AO1167B as a potential probiotic supplement. Strain identification was confirmed via morphological and cultural techniques, and genomic characterization utilized 16S RNA and whole genome sequencing to identify antimicrobial resistance and virulence factors. Phenotypic analysis included disk diffusion tests for antimicrobial resistance. Cytotoxicity and haemolytic activity were assessed using Vero cells and erythrocytes. This phase I, double-blind, placebo-controlled clinical trial evaluated Heyndrickxia coagulans AO1167B through in vivo analyses Healthy adult volunteers were randomized into Heyndrickxia coagulans AO1167B and placebo groups, with a study duration of 60 days. Daily consumption of the test capsule or placebo was monitored through clinical and haematological evaluations, adverse event (AE) tracking, and health surveys. The genome of Heyndrickxia coagulans AO1167B showed no concerning features. Disk diffusion tests revealed no antimicrobial resistance. The strain exhibited no cytotoxic or haemolytic activity, indicating in vitro safety. No significant differences were observed in clinical or haematological parameters between the Heyndrickxia coagulans AO1167B and placebo groups. The most frequent adverse event was gas, which decreased over time. Heyndrickxia coagulans AO1167B is safe and well-tolerated for daily consumption over 60 days in healthy adults, supporting its potential for further probiotic development

Registration and Update

Section to complete information about the name of Primary Registry, date of registration and the unique ID number assigned by the registry (RPCEC).

Primary registry:

RPCEC

Unique ID number:

RPCEC00000430

Date of Registration in Primary Registry:

07/08/2023

Record Verification Date:

2025/12/12

Next update date:

2026/12/12

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Safety evaluation of Bacillus coagulans AO1167 for its use as a probiotic in humans

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