Safety and Tolerability of Bacillus Subtilis MB40 in Healthy Adult Volunteers

Single Center, Clinical Trial Examining the Safety and Tolerability of a Bacillus Subtilis Probiotic in Healthy Adult Volunteers in a Single-Blind Design

This study is a single-blind, placebo-lead in design examining the safety and tolerability of a probiotic, Bacillus subtilis MB40. Subjects received a 7-day placebo BID lead-in and a 21-day BID course of Bacillus subtilis MB40. GI questionnaires and Bristol stool charts along with evaluation of any medically significant changes, based on physical examination findings, clinical laboratory tests and vital signs assessments were used to determine the safety and tolerability of MB40.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Dietary supplement: Bacillus subtilis MB40

• Study Type: Observational
• Enrollment (Actual): 30

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Human volunteers meeting eligibility criteria listed above.

Description

Inclusion Criteria:

1. Normal, healthy adult volunteers aged 18 to 55 years.
2. BMI of 18 to 32 kg/m2 (inclusive)
3. Have no clinically significant findings on screening evaluations (clinical, laboratory)

4. If female, participant is not of child bearing potential, which is defined as females who have had a hysterectomy or oophorectomy, bilateral tubal ligation or are post-menopausal (natural or surgically with > 1 year since last menstruation) OR

   Females of childbearing potential must agree to use a medically approved method of birth control and have a negative urine pregnancy test result. Acceptable methods of birth control include:

   • Hormonal contraceptives (stable for 1 month) including oral contraceptives, hormone birth control patch (Ortho Evra), vaginal contraceptive ring (NuvaRing), injectable contraceptives (Depo-Provera, Lunelle), or hormone implant (Norplant System)
   • Double-barrier method
   • Intrauterine devices
   • Non-heterosexual lifestyle or agrees to use contraception if planning on changing to heterosexual partner(s)
   • Vasectomy of partner (shown successful as per appropriate follow-up)
5. Able to comprehend and willing to sign an Informed Consent Form (ICF).

Exclusion Criteria:

1. History or clinical manifestations of significant metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders.
2. Current or recent history (<30 days prior to Screening) of a clinically significant bacterial, fungal, or mycobacterial infection.
3. Frequent GERD, indigestion, nausea, or vomiting (1 or more days per week).
4. Frequent abdominal pain/cramps or bloating (1 or more days per week).
5. Frequent constipation, diarrhea, or alternating constipation/diarrhea (1 or more days per week).
6. Abdominal pain before bowel movements that is relieved with defecation (most bowel movements).
7. Abdominal complaints often worsened by worry or tension (1 or more days per week).
8. Medical diagnosis of esophagitis, gastritis, ulcers, inflammatory bowel disease, gastrointestinal cancer, celiac disease, or irritable bowel syndrome.
9. Recent gastrointestinal bleeding (hematemesis, hematochezia, melena in past 3 months) or anemia in the past 3 months.
10. Unintentional weight loss of 10 lbs or more in the past 3 months.
11. Screening GI Questionnaire Score of ≥ 4 for any single item.
12. Current clinically significant viral infection
13. History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin
14. Resting heart rate less than 45 bpm or greater than 100 bpm.
15. History of unstable ischemic heart disease or uncontrolled hypertension (blood pressure >150/90 mm Hg)
16. History of stomach or intestinal surgery, except that appendectomy and/or cholecystectomy will be allowed.
17. Presence of a malabsorption syndrome possibly affecting drug/Product absorption (e.g., Crohn's disease or chronic pancreatitis)
18. History of alcoholism or drug addiction within 1 year prior to Screening, or current alcohol or drug use that, in the opinion of the investigator, will interfere with the subject's ability to comply with the dosing schedule and study evaluations.
19. Use of any tobacco-containing or nicotine-containing products (including cigarette, pipe, cigar, chewing tobacco, nicotine patch, or nicotine gum) more frequently than 50 cigarettes per week within 2 months prior to Screening or > 20 per week from screen through the end of the study
20. Current treatment or treatment within 30 days or 5 half-lives (t ½) prior to the first dose of study product with another investigational product or current enrollment in another investigational drug protocol at the time of screening.
21. Use of any over-the-counter, prescription, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant derived preparations), within 7 days prior to study entry, unless deemed acceptable by the Investigator.
22. Use of greater that 2 units per day of alcohol-containing or caffeine-containing foods or beverages within 72 hours prior to study entry and throughout the duration of the study.
23. Donation of blood in excess of 500 ml within 4 weeks prior to study entry or of plasma within 2 weeks prior to Screening.
24. Receipt of blood products within 3 months prior to study entry.
25. Subjects who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Bacillus subtilis MB40; 1-week placebo (maltodextrin and excipients) lead-in followed by MB40 intervention	Dietary supplement: Bacillus subtilis MB40; 1-week placebo (maltodextrin and excipients) lead-in followed by 250 mg capsule (5 billion CFU/capsule) administered twice daily for 21 days; Other Names: OPTI-BIOME MB40

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of adverse events	GI Questionnaire and weekly in person assessment of adverse events	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly mean of daily frequency of GI symptoms	GI symptom frequency and severity questionnaire	4 weeks
Weekly mean of daily severity of GI symptoms	GI symptom frequency and severity questionnaire	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of bowel movements	Bristol Stool Chart questionnaire	4 weeks
Incidence of clinically significant abnormal vital signs		Screening and day 29
Incidence of clinically significant abnormal complete blood panel		Screening and day 29

Collaborators and Investigators

• Sponsor: BIO-CAT Microbials, LLC
• Collaborators: Prism Research LLC
• Investigators: Study Director: Mark Matson, MD, Prism Research LLC

Publications and helpful links

General Publications

• Spears JL, Kramer R, Nikiforov AI, Rihner MO, Lambert EA. Safety Assessment of Bacillus subtilis MB40 for Use in Foods and Dietary Supplements. Nutrients. 2021 Feb 25;13(3):733. doi: 10.3390/nu13030733.

Helpful Links

• Full text link

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2015
• Primary Completion (Actual): December 17, 2015
• Study Completion (Actual): December 17, 2015

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): February 10, 2022
• Last Update Submitted That Met QC Criteria: January 27, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: BCT-100-000

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