Safety and Tolerability of Oral Supplementation With 1 mg of KGA-10 Daily (a Novel Environmentally-derived Mycolicibacterium) - a Pilot Study

Clinical Trial of Oral Supplementation With Novel Mycolicibacterium (KGA-10)

The goal of this clinical trial is to learn if a novel strain of heat-killed Mycolicibacterium that is being considered by the International Code of Nomenclature of Prokaryotes (ICNP) as candidate species and type strain "Candidatus Mycolicibacterium petrae" KGA-10 (KGA-10) is safe and well tolerated for healthy adults. This novel Mycolicibacterium species is also referred to as NeuroAlly and MTC 0012. The questions it aims to answer are: 1) is KGA-10 associated with adverse side effects and 2) is KGA-10 well tolerated.

Researchers will compare daily KGA-10 (1 mg mixed with microcrystalline cellulose in capsule form) to a placebo (microcrystalline cellulose in capsule form, but contains no KGA-10) to examine any adverse side effects and tolerability of KGA-10 relative to placebo.

Participants will take KGA-10 or a placebo everyday for 1 week and keep a daily log of their supplement intake that includes the time of day. Participants will complete the Generic Assessment of Side Effects - Probiotics (GASE-P)* survey to assess side effects experienced during the trial both related and not related to the supplement at baseline, 2 hrs following their first dose, 24 hrs following their first dose, and on day-7. Participants will complete the Treatment Satisfaction Questionnaire for Medication (TSQM) survey to assess tolerability/satisfaction of the supplement at 2 hrs following their first dose, 24 hrs following their first dose, and on day-7.

*Survey was modified by replacing the work "probiotic" with "postbiotic" for accuracy.

Enrolled participants reported to the study site to complete onboarding, which included baseline surveys, receipt of their 1-week supply of study supplement, and ingest their first dose of their supplement. The active treatment group received capsules containing 1 mg of KGA-10 and excipient (microcrystalline cellulose) while the placebo group received capsules of excipient only. Participants remained at the study site for two hours to be under the supervision of a medical professional to evaluate and respond to any anaphylactic, allergic, or adverse events (AE). Following the two-hour observation period, participants were cleared for release by the medical professional and provided with the 24 hr contact information (mobile phone number and email address) to reach the study principal investigator (PI) and medical professional. They were then released from the study site with the remaining 1-week supply of their supplement and completed the rest of the trial remotely via the data capture platform. Participants were instructed to seek immediate medical attention for any serious adverse events and to report any additional concerns to the study PI and/or medical professional. Additionally, participants had 24 hr access to an AE reporting mechanism on the data capture platform dashboard. Participants were informed that missed doses were not to be replaced with a double dose the following day.

Inclusion Criteria:

• Healthy individuals between the ages of 18 and 65
• Able to provide informed consent
• Willing to take a daily supplement
• Willing to complete at-home finger prick - blood spot samples on three occasions
• English speaking

Exclusion Criteria:

• Inability to adequately respond to questions regarding the informed consent procedure
• Currently involved in the criminal justice system as a prisoner or ward of the state
• Non-English speaking
• Current (past month) alcohol or substance abuse or dependence
• Lifetime history of bipolar disorder or psychosis
• Receiving intravenous, intramuscular, or oral antibiotics within the last month
• Receiving medications that interfere with gut motility (opiates, loperamide, stool softeners)
• Presence of central venous catheters (CVCs)
• Gastrointestinal (GI) barriers as identified by the 2-week run-in period as determined by the study team (e.g., daily GI discomfort with frequent diarrhea prior to supplementation)
• Participation in conflicting interventional research protocol
• Vital signs outside of acceptable range (i.e., blood pressure >160/100, oral temperature >100°F, pulse >100)
• Use of any of the following drugs within the last 6 months: systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral); oral, intravenous, intramuscular, nasal or inhaled corticosteroids; cytokines or cytokine inhibitors; methotrexate or immunosuppressive cytotoxic agents
• Acute disease at the time of enrollment (defer sampling until the participant recovers-acute disease is defined as the presence of a moderate or severe illness with or without fever)
• Chronic, clinically significant (unresolved, requiring ongoing medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality
• History of cancer except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision
• Positive test for human immunodeficiency virus (HIV), Hepatitis B virus, or Hepatitis C virus
• Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection
• Major surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time
• Regular urinary incontinence necessitating use of incontinence protection garments
• Female who is pregnant or lactating
• Treatment for or suspicion of ever having had toxic shock syndrome
• Those receiving immunosuppressive drugs or treatment including antineoplastic therapy, post-transplantation immunosuppressive therapy, and/or radiation therapy