Clinical trial NCT06389539: Synbiotic to Attenuate Resorption of the Skeleton
Official title: A Randomized, Double-Blind, Placebo-Controlled, Clinical Food Trial of Probiotic/Prebiotic Medical Food for the Dietary Management of Age Related Bone Loss
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Osteoporosis
Inflammation
Aging
Keywords: Dietary probiotics
Dietary prebiotics
Gut microbiome
Older women
Randomized Controlled Trial
Lead sponsor: Hebrew SeniorLife
Sponsor class: OTHER
Collaborators: name: Solarea Bio, Inc
name: Beth Israel Deaconess Medical Center
name: Tufts University
name: MaineHealth
First posted: 2024-04-29
Enrollment: 220
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized to either SBD111 medical food or placebo capsules for a period of 18 months.
Primary purpose: OTHER

Brief summary: This randomized, double blind, placebo controlled clinical trial will test the efficacy of a probiotic/prebiotic combination ("synbiotic") on the skeleton in older women.

Detailed description: There are currently no consistent guidelines on how middle aged and older adults can maintain healthy bone mass as they age. Hence, there is an unmet need for safe and effective dietary interventions for the metabolic processes underlying bone loss. The objective of this project, is to test the efficacy of a probiotic/prebiotic combination or synbiotic i.e. Solarea Bio defined microbial assemblage 111 (SBD111) medical food on the skeleton of older women.

Aim 1: To determine the effect of 18 months of daily intake of SBD111 medical food on the primary outcome of lumbar spine dual energy x-ray absorptiometry (DXA) bone mineral density (BMD) and secondary outcomes (Biomechanical Computed Tomography analysis (BCT)-derived vertebral compressive strength, volumetric BMD (vBMD), and markers of bone turnover) in women.

Hypothesis 1a: BMD, vertebral compressive strength, and vBMD will be greater in women randomized to SBD111 medical food compared to placebo.

Hypothesis 1b: Biochemical markers of bone turnover will decrease with SBD111 medical food use compared to placebo.

Aim 2: To determine the effect of 18 months of daily intake of SBD111 medical food on markers of inflammation and gut microbiome function (secondary outcomes) in women.

Hypothesis 2a: Markers of inflammation \[interleukin 17A (IL17A) and tumor necrosis factor alpha (TNF-α)\] will be reduced with SBD111 medical food use compared to placebo.

Hypothesis 2b: Functional genes and pathways related to fiber breakdown (glycosyl hydrolases), menaquinone 7 production, and short chain fatty acid (SCFA) production, will be enriched in stool metagenomes and upregulated in stool metatranscriptomes from those receiving SBD111 medical food compared to placebo.

Eligible women will be randomized to SBD111 medical food versus placebo capsules for 18 months. Assessments will be made at the in-person baseline visit, 9-month and 18-month follow-up visits as well as monthly telephone calls.

The primary outcome is lumbar spine BMD (g/cm2) and secondary outcomes include vertebral compressive strength (N), vBMD (g/cm3), and bone biomarkers.

Intent-to-treat analysis will be conducted for all endpoints.

Eligibility criteria: Inclusion Criteria:

1. Provide written informed consent
2. Stated availability throughout entire study period and willingness to fulfill all details of the protocol
3. Age 60 years and above
4. DXA-BMD of the hip and spine (T-score) \> -2.5. Women with a BMD T score ≤ -2.5 (i.e. women with low BMD indicating osteoporosis) will also be considered if they have decided not to accept the standard of care with use of osteoporosis medications for the entire duration of their participation in the study.
5. 25-hydroxy vitamin D ≥ 20 ng/mL
6. Normal renal function (eGFR \>50 ml/min)
7. Have chosen to not accept the standard of care with use of osteoporosis medications for the duration of the study.
8. Willing to comply with protocol and report on compliance and side effects during study period.

Exclusion Criteria:

1. BMI greater than equal to 35 kg/m2.
2. Participants consuming dietary supplements (fish oil, probiotics/prebiotics, and fiber) in the prior month, and and unwilling to avoid these supplements for the duration of the study.
3. Known or suspected allergies to probiotics, gelatin, rice, edible fruit extract or berries.
4. We will exclude women using antibiotics in the past 3 months but those placed on an antibiotic after enrollment, will be retained.
5. History of drug and/or alcohol abuse at the time of enrolment.
6. Presence of any of the following:

   1. History of other bone disorders (e.g. Paget's disease)
   2. History of major low-trauma fragility fractures (hip, forearm, humerus, spine) since the age of 50 years
   3. History of cancer other than skin cancer \<5 years in remission, autoimmune disease, immune problems such as AIDS, type 1 or 2 diabetes, gastrointestinal disorders (ulcerative colitis, inflammatory bowel disease)
   4. History of colon resection, any disease that could interfere with the intestinal barrier function such as ulcerative colitis, irritable bowel syndrome or Crohn's disease
   5. Women with untreated hyperparathyroidism
   6. History of chronic antibiotic use
   7. History of bariatric surgery
   8. History of partial colectomy
   9. History of problems with pancreas
   10. History of history of chronic Hepatitis B or Hepatitis C, cirrhosis, fatty liver (nonalcoholic steatohepatitis; NASH) or chronic liver disease
   11. History of problems with your heart valves, endocarditis, or previously had a valve replacement
   12. Currently have problems with bone marrow such as myelodysplastic syndrome or anemia requiring transfusions
   13. Women with spine abnormalities that would interfere with the assessment of BMD
   14. Current smoking or use of nicotine products within the past 6-months
   15. Major surgery or endoscopy within last 3 months
   16. Coloscopy planned in the next 18-months and unwilling to reschedule it
   17. Indwelling catheter, implanted hardware/prosthetic device or feeding tube
   18. Any medical condition that could interfere with the conduct of the study
7. Treatment with calcitonin, estrogens, selective estrogen receptor modulators, progestins, anabolic steroids, or glucocorticoids in the past 6 months
8. Treatment with bisphosphonates in the past 3 yrs
9. Previous treatment with parathyroid hormone (PTH), abaloparatide, romosozumab or denosumab in the last year or current coumadin use.
10. Participation in other bone, diet, autoimmune, or GI related clinical trials in the last 6 months. If the subject has been in a recent experimental trial, these must have been completed not less than 60 days prior to this study.
11. Participants who plan on changing diet and/or exercise regime during trial participation.
12. Screening laboratory tests greater than upper normal limit (ULN) or less than lower normal limit (LLN):

    * 25-hydroxy vitamin D \<20 ng/mL
    * Renal dysfunction (eGFR ≤50 ml/min)
13. Seated blood pressure greater than equal to 160 mm Hg or seated diastolic BP greater than equal to 100mm Hg.
14. Short Blessed Test score \>10 or judged by the research staff as unable to follow the study protocol
15. Current treatment or previous with Glucagon-like peptide (GLP-1) agonists in the last one year.
16. Any other condition that in the opinion of the investigator or study clinician would jeopardize the safety or rights of the volunteer participating in the study or would make it unlikely the volunteer could complete the study.

Primary outcomes:
measure: Lumbar spine BMD (g/cm2)
timeFrame: Change over 18 months
Secondary outcomes:
measure: Vertebral compressive strength (N)
timeFrame: Change over 18 months
measure: volumetric BMD
timeFrame: Change over 18 months
measure: C-terminal cross-linked telopeptide of type I collagen (β-CTX)
timeFrame: Change over 18 months
measure: Procollagen Type I Intact N-terminal Propeptide (P1NP)
timeFrame: Change over 18 months
Other outcomes:
Locations:
city: Roslindale
country: United States
facility: Hebrew SeniorLife
state: Massachusetts
Study officials:
affiliation: Hebrew SeniorLife
name: Shivani Sahni, PhD
role: PRINCIPAL_INVESTIGATOR
References: