Menopause Related Conditions, Osteopenia, Osteoporosis, Probiotic Intervention, Synbiotics
Conditions
Keywords
Probiotic, Synbiotic, Bone Loss, Osteopenia, Osteoporosis, Fully Remote
Brief summary
The purpose of this study is to determine whether a modified formulation and daily intake schedule of SBD111 results in similar levels of probiotic microbes in the gut compared with the currently used formulation. SBD111 is a food made of probiotic microbes (bacteria and yeast) and prebiotic dietary fibers (a form of fiber obtained from diet). SBD111 is a medical food used for the dietary management of postmenopausal bone loss.SBD111 was previously found to be safe and well tolerated in a human clinical safety study and a clinical efficacy study. Study participation will include a screening virtual visit, periodic remote questionnaires and check-in calls, and three at-home stool swab sample collections. Eligible participants will be assigned to one of two SBD111 study groups evaluating different formulations and dosing schedules. Each day for a 28-day period, they will take (i) two capsules once daily or (ii) two capsules twice daily (morning and evening), depending on the study group assigned. Investigators will collect demographic information and will ask questions related to dietary intake, bowel habits, and health history. Upon enrollment into the study, participants will receive six at-home stool sample collection kits, two each for baseline, Week 1, and Week 4 analysis. Samples will be collected at home and mailed to a Sōlaria Biō for analysis of the bacterial community that lives in the intestine (the gut microbiome). During the study, participants will also be asked to complete brief questionnaires related to gastrointestinal symptoms, cognitive function, well-being, and sleep. On days 7 and 28 of the study, they will be asked to complete a brief adherence questionnaire and discuss any adverse (negative) events. All participants will receive compensation in the form of gift cards for completing study procedures and returning stool samples. Participants will receive a $50.00 gift card after completing the Week 1 study procedures and after receipt of the mailed baseline and Day 7 stool swab samples. Participants will receive a $150.00 gift card after completing the Week 4 study procedures and after receipt of the mailed Week 4 stool swab sample.
Detailed description
The human gut microbiome plays an important role in immune regulation, inflammatory signaling, and skeletal homeostasis. Alterations in the gut microbiome have been associated with multiple chronic conditions, and microbiome-directed interventions such as probiotics and prebiotics have been investigated for their effects on host metabolism and immune function. Preclinical and clinical findings suggest that microbiome-derived metabolites, including short-chain fatty acids, may help regulate pathways involved in bone remodeling and inflammatory balance. SBD111 is a defined microbial assemblage composed of Lactobacillus brevis, Lactobacillus plantarum, Leuconostoc mesenteroides, and Pichia kudriavzevii in combination with oligofructose, dried blueberry powder, vitamin D3, and formulation excipients. The currently marketed formulation is administered as two capsules twice daily. A modified formulation has been developed to deliver the same total daily microbial load and strain composition in two capsules taken once daily. The modified formulation uses a larger capsule format and a reduced amount of dried blueberry powder while maintaining comparable microbial exposure. In preclinical studies, SBD111 was associated with maintenance of bone mineral density and favorable effects on markers related to bone turnover and inflammatory signaling. Prior clinical evaluation in healthy adults and postmenopausal women indicated that SBD111 was safe and well tolerated. These data support further evaluation of formulation and dosing optimization. The purpose of this study is to compare gastrointestinal exposure to SBD111 microbial strains following administration of the currently marketed twice-daily formulation and the modified once-daily formulation in healthy adults. The key objective is to determine whether once-daily administration of the modified formulation results in fecal abundance of SBD111 strains comparable to that observed with twice-daily administration of the currently marketed formulation. Healthy adults aged 35 years and older will complete a 28-day study period. Baseline stool collection will occur before first product administration. Stool samples will be collected at baseline, Day 7, and Day 28 and analyzed using strain-specific quantitative polymerase chain reaction to assess fecal abundance of the four SBD111 strains. Gastrointestinal tolerability, adherence, adverse events, and participant-reported measures of sleep, cognitive function, and well-being will also be assessed during the study period. Study product will be shipped to participants, and study procedures will be conducted remotely. Samples will be collected at home and returned by mail for laboratory analysis. Laboratory personnel performing sample analysis will remain blinded to treatment assignment. Participant confidentiality will be protected through coded identifiers and secure storage of study records.
Interventions
COMBINATION_PRODUCTSBD111(current formulation)
SBD111 (current formulation) is a combination of probiotic bacteria and yeast as well as prebiotic fibers taken twice daily
COMBINATION_PRODUCTSBD111 (new formulation)
SBD111 (new formulation) is a combination of probiotic bacteria and yeast as well as prebiotic fibers taken once daily
Sponsors
Solarea Bio, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Masking description
While this interventional trial is open label, the researchers performing the product abundance analyses will be blinded to the treatment groups.
Eligibility
Sex/Gender
ALL
Age
35 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
• Provide written informed consent. * Stated availability throughout entire study period and willingness to fulfill all details of the protocol. * Age 35 years or older. * Be in general good health as determined by a screening evaluation within 30 days of the first administration of SBD111 medical foods. * Willing to comply with protocol and report on compliance and side effects during study period. * Body Mass Index between 18.5 and 40kg/m2.
Exclusion criteria
* • Are currently taking probiotic or prebiotic supplements or have taken them in the past 30 days. If participant is willing to stop taking probiotic or prebiotic supplement for 30-days, they can be re-screened for eligibility and enrollment after consent. * Unwilling to avoid probiotics/prebiotics supplements for the duration of the study. * Known or suspected allergies to probiotics, maltodextrin, or berries. * Received oral or parenteral antibiotics within 30 days of enrollment or prescribed antibiotics on the day of enrollment. * Major surgery on the intestines or endoscopy within last 3 months. * History of drug and/or alcohol abuse at the time of enrollment. * Presence of any of the following based on participant reported health history: * Clinically significant systems abnormalities based on screening questionnaire. * Indwelling catheter or feeding tube. * Febrile illness (oral temperature \>37 degrees Celsius) or one or more episodes of diarrhea within 72 hours of baseline (first administration of study article). * Active bowel leak, acute abdomen, colitis, or active GI disease or history of gastric or intestinal dysmotility, slowed transit time, variable small intestinal permeability, pancreatitis, or inflammatory bowel disease. * History of Hepatitis B or Hepatitis C infections, cirrhosis, or chronic liver disease. * Underlying structural heart disease or previous history of endocarditis or valve replacement. * Immunosuppression including HIV positive, solid organ or stem cell transplant recipient, receiving any oral or parenteral immunosuppressive therapy. * History of Celiac disease. * History of cancer. a. Excluding non-melanoma skin cancers or cancer more than 10 years ago. * History of autoimmune disease and taking any immunosuppressant drugs. * Active tuberculosis. * Pregnant, planning on becoming pregnant within the next 2 months, breastfeeding, positive urine pregnancy test within 24 hours of first administration of DMA. * Participants may be excluded if, in the investigator's opinion, there is evidence of cognitive impairment or dementia which is sufficient to interfere with informed consent or adherence to the study protocol. Four questions will be asked during the informed consent process to confirm participant's understanding and ability to comply. (See section 8.3) * Any other condition that in the opinion of the investigator would jeopardize the safety or rights of the volunteer participating in the study or would make it unlikely the volunteer could complete the study. * Bowel movement frequency less than one per 36-hour period. * If the subject has been in a recent experimental trial, these must have been completed not less than 30 days prior to this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Composite fecal abundance of SBD111 microbial strains measured by strain-specific qPCR | From enrollment out to 28 days of consuming the product | Composite fecal abundance of the four SBD111 microbial strains (Lactobacillus brevis, Lactobacillus plantarum, Leuconostoc mesenteroides, and Pichia kudriavzevii) assessed by strain-specific qPCR and expressed as log10(copies/16S copies). The composite endpoint is the mean of the four log10-transformed strain-specific values. Non-inferiority of the modified formulation vs. the currently marketed formulation will be declared if the upper bound of the 95% CI for the between-group difference does not exceed 0.5 log units. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Gastrointestinal tolerability assessed by Gastrointestinal Tolerability Questionnaire (GITQ) | From enrollment through 28 days of product consumption | Gastrointestinal tolerability assessed using the Gastrointestinal Tolerability Questionnaire (GITQ), which records the presence and severity of gastrointestinal symptoms, at baseline, Day 7, and Day 28. |
| Fecal abundance of individual SBD111 microbial strains by strain-specific qPCR | From enrollment through 28 days of product consumption | Relative fecal abundance of each individual microbial strain contained in SBD111 -- Lactobacillus brevis, Lactobacillus plantarum, Leuconostoc mesenteroides, and Pichia kudriavzevii -- assessed separately by strain-specific qPCR and expressed as log10(copies/16S copies) at Days 7 and 28. Baseline-adjusted abundance for each strain will be compared between the modified (once-daily) and currently marketed (twice-daily) formulations using the same non-inferiority margin of 0.5 log units applied to the primary composite endpoint. |
| Gastrointestinal symptoms assessed by Patient-Reported Outcomes Measurement Information System Gastrointestinal Gas and Bloating 13a score | From enrollment through 28 days of product consumption | Gastrointestinal symptoms assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.1 - Gastrointestinal Gas and Bloating 13a. PROMIS response-pattern scoring is preferred; for fully completed forms, raw summed scores range from 13 to 59. Higher scores indicate worse gas and bloating symptoms. |
| Gastrointestinal symptoms assessed by Patient-Reported Outcomes Measurement Information System Gastrointestinal Constipation 9a score | From enrollment through 28 days of product consumption | Gastrointestinal symptoms assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.0 - Gastrointestinal Constipation 9a. For fully completed forms, raw summed scores range from 12 to 45. Higher scores indicate worse constipation symptoms. |
| Gastrointestinal symptoms assessed by Patient-Reported Outcomes Measurement Information System Gastrointestinal Diarrhea 6a score | From enrollment through 28 days of product consumption | Gastrointestinal symptoms assessed using the Patient-Reported Outcomes Measurement Information System (PROMIS) Scale v1.0 - Gastrointestinal Diarrhea 6a. For fully completed forms, raw summed scores range from 8 to 30. Higher scores indicate worse diarrhea symptoms. |
Contacts
CONTACTAlicia E Ballok, PhD
CONTACTMark Charbonneau, PhD
PRINCIPAL_INVESTIGATORAlicia E Ballok, PhD
Solaria Bio
Outcome results
None listed