Synbiotic to Attenuate Resorption of the Skeleton (STARS)

A Randomized, Double-Blind, Placebo-Controlled, Clinical Food Trial of Probiotic/Prebiotic Medical Food for the Dietary Management of Age Related Bone Loss

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

Study Overview

• Status: Not yet recruiting
• Conditions: Inflammation; Aging; Osteoporosis
• Intervention / Treatment: Other: Placebo; Other: SBD111 medical food

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.

• Study Type: Interventional
• Enrollment (Estimated): 220
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shivani Sahni, PhD; Phone Number: 617-971-5382; Email: ShivaniSahni@hsl.harvard.edu
• Study Contact Backup: Name: Evelyn O'Neill; Phone Number: 617-697-6599; Email: oneill@hsl.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Roslindale, Massachusetts, United States, 02131
      • Hebrew SeniorLife
      • Contact: Kathryn Tasker; Phone Number: 617-971-5351; Email: KathyTasker@hsl.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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
5. 25-hydroxy vitamin D ≥ 20 ng/mL
6. Normal renal function (eGFR >50 ml/min)
7. 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 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. Current 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. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SBD111 medical food; This group will receive SBD111 medical food capsules to be consumed over 18 months.	Other: SBD111 medical food; SBD111 medical food is a defined microbial assemblage (DMA) consisting of oligofructose and dried berry powder (prebiotics), a Pseudomonas fluorescens, a Lactobacillus brevis, a Leuconostoc mesenteroides, a Lactobacillus plantarum, and a Pichia kudriavzevii (yeast).
Placebo Comparator: Placebo; This group will receive placebo capsules to be consumed over 18 months.	Other: Placebo; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lumbar spine BMD (g/cm2)	BMD of the lumbar spine (L1-L4) will be measured at the baseline exam, 9-month, and 18-month final follow-up visit	Change over 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vertebral compressive strength (N)	Quantitative computed tomography (QCT) scans acquired at baseline and 18-months will be used to estimate vertebral compressive bone strength using Biomechanical Computed Tomography (BCT, VirtuOst, O.N. Diagnostics, Berkeley, CA).	Change over 18 months
volumetric BMD	Measurements of integral and vertebral trabecular vBMD at L1-L3.	Change over 18 months
C-terminal cross-linked telopeptide of type I collagen (β-CTX)	A biochemical marker of bone resorption	Change over 18 months
Procollagen Type I Intact N-terminal Propeptide (P1NP)	A biochemical marker of bone formation	Change over 18 months

Collaborators and Investigators

• Sponsor: Hebrew SeniorLife
• Collaborators: Beth Israel Deaconess Medical Center; Tufts University; MaineHealth; Solarea Bio, Inc
• Investigators: Principal Investigator: Shivani Sahni, PhD, Hebrew SeniorLife

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): April 1, 2028

Study Registration Dates

• First Submitted: April 24, 2024
• First Submitted That Met QC Criteria: April 24, 2024
• First Posted (Actual): April 29, 2024

Study Record Updates

• Last Update Posted (Actual): April 29, 2024
• Last Update Submitted That Met QC Criteria: April 24, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Gut microbiome; Older women; Dietary probiotics; Dietary prebiotics
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Inflammation; Osteoporosis
• Other Study ID Numbers: Pro00070958

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