Clinical trial NCT06845995: Effects of a Synbiotic Supplement on Metabolic & Cognitive Outcomes Among Older Adults
Official title: The Effects of a Synbiotic Supplement on Metabolic & Cognitive Outcomes and Vitamin D Receptor Variants on Bone Health Among Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Older Adults
Bioelectrical Impedance
Appetite Hormones
Metabolic Health
Body Composition Measurement
Cognitive Health
Keywords: Synbiotic supplement
Vitamin D receptor variants
Body composition
Bone health
Metabolic outcomes
Muscle strength
Appetite hormons
Cognitive health
Lead sponsor: Texas Tech University
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 32
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Potential subjects will be informed of the study through a study being conducted at Nutrition and Metabolic Health Initiative and at local exercise centers for senior adults and independent living communities by flyers and social media, which will give interested subjects contact information. Once interested subjects communicate with the research team, a research personnel will begin screening process by phone or in-person to see if subject qualifies based on inclusion/exclusion criteria. A research team member will schedule an in-person appointment for subjects that qualify for the study. The research team will ask the subjects to sign a consent form in-person prior to the baseline appointment, Once the consent is signed, random assignment to the study group and data collection will begin.
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to investigate the effects of a prebiotic and probiotic supplement on metabolic, cognitive, and muscle health in older adults.

Participants in the study will be older adults who will receive a prebiotic and probiotic supplement containing different strains of Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus gasseri. The study will collect data at baseline and after 3 months of supplementation to compare the effects on metabolic, cognitive, and muscle health. Additionally, genetic variants associated with vitamin D deficiency and muscle phenotypes will be identified in this population.

Detailed description: Objective one of this research is to determine if there are significant differences in metabolic and muscle health including anthropometrics, biochemical, and muscle quality indices using a prebiotic and probiotic supplement containing different strains of Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus gasseri in older adults.

There are many physiological changes that occur with aging, which include alterations in the gut microbiota. Gut dysbiosis has also been associated with aging as well as immunity and metabolic alterations such as cardiovascular disease, low-grade inflammation and frailty (Badal et al., 2020). Some studies have shown that probiotics can be a potential therapy to restore the balance of healthy human intestinal function and gut bacterial composition of the gut microbiota because they contain microorganisms naturally found in the human microfiora (Lee et al., 2020). The gut microbiota and its associations with aging are related to clinical and metabolic improvements (Badal et al., 2020). Probiotics and functional foods may have a beneficial effect on the gut by increasing the levels of bifidobacteria or modifying subpopulations of lactobacilli (Ale \& Binetti, 2021). The gut microbiota is very important to human metabolism because of its' contribution of enzymes that are not encoded by the human genome, for example, the breakdown of polysaccharides, polyphenols, and synthesis of vitamins (Rowland et al., 2018). It is important to identify the effect that environmental factors, dietary factors (pre and probiotics, etc.), and their combined effect on metabolic and muscle health such as body composition, blood parameters, and muscle quality. Literature shows the benefits of synbiotic (pre and probiotic formula) on several cardiovascular risk factors including lipid and glycemic metabolic parameters in elderly patients (Cicero et al.,2021). However, the optimal timing for supplementation, duration of treatment, as well as the type and dose of the prebiotic and synbiotic to be used needs to be contemplated (Ale \& Binetti., 2021).

• Objective two will be to identify variant genes associated with vitamin D deficiency and muscle phenotypes among older adults. Genetic variants for vitamin D deficiency have not been thoroughly studied in older adults. Significant associations have been identified between VDR polymorphism and muscle performance phenotypes although results were conflicting (Pratt et al., 2020). Several allelic variations have been described in the VDR gene, including restriction fragment length polymorphisms, such as Fok1 (C/T) (rs10735810/rs2228570) and Bsm1 (A/G) (rs1544410) (Berry \& Hypponen, 2011). This will study the effect of genetic variations on the nutritional requirements of an individual and can provide some prediction to help with prevention as well as contribute to personalized dietary management (Crovesy \& Rosado, 2019). It could also lead to improved clarification on the association between vitamin D status and patient outcomes following bariatric surgery (Berry \& Hypponen, 2011; Davies et al., 2018).

Objective three will be to identify if there are significant differences in cognitive health including memory, attention, executive functioning, biochemical, and psychomotor skills indices using a prebiotic and probiotic supplement containing different strains of Lactobacillus acidophilus, Bifidobacterium longum, Lactobacillus rhamnosus, and Lactobacillus gasseri in older adults. There are many cognitive changes that occur with aging. Probiotics have been proposed to improve cognitive impairment via the gut-brain axis in patients and experimental animal models (Kim et al, 2021), (Asaoka et al, 2022), (Handajani et al, 2022). However, the beneficial role of synbiotics in brain function of healthy older adults remains unclear (Kim et al, 2021).

Objective one:

Based on 0- to 3-month data collection for baseline and post-intervention physiological outcomes: • What are the differences between basal and 3-month post synbiotic supplementation with regard to the following measurements (biological markers, gut QOL, genetic markers, anthropometric variables).

Based on 3-month supplementation of synbiotics from baseline to 3 months:

Does synbiotic supplementation for 3 months (from baseline to 3rd month) improve gut bacterial functions and gut quality of life in older adults compared to no supplementation?

* If participant report improvement in gut quality of life, are these associated with other physiological indicators of metabolic health (i.e. biological markers, genetic markers, anthropometric variables)?
* Is there an association between improved gut microbiota and gut quality of life and physiological indicators of metabolic health?
* Are any associations observed between improved gut microbiota and biological markers, guts QOL, genetic markers, anthropometric variables?

Objective two:

* What is the prevalence of Vitamin D Receptor (DR) genetic variants in this population?
* Are VDR genetic variants associated with vitamin D deficiency and muscle quality (measured by serum levels, body composition and grip strength)?

Objective three:

Based on 0- to 3-month data collection for baseline and post-intervention physiological outcomes:

What are the differences between basal and 3-month post synbiotic supplementation with regard to the following measurements (biological markers, cognitive function tests, and psychomotor skills)?

Based on 3-month supplementation of synbiotics from baseline to 3 months:

If participant report improvement in gut quality of life, are these associated with other indicators of cognitive health (i.e. biological markers, cognitive function tests, and psychomotor skills)?

Is there an association between improved gut microbiota and gut quality of life and indicators of cognitive health?

Are any associations observed between improved gut microbiota and biological markers, cognitive function tests, and psychomotor skills?

Eligibility criteria: Inclusion screening:

* ≥65 years of age
* Male and female
* Physically active as defined by participating in activity beyond baseline activities of daily living (dressing, bathing, toileting, continence, eating, and transferring).

Exclusion screening:

* \<65 years of age
* Intake of nicotine, alcohol, and/or drugs such as amphetamines, cocaine, marijuana, and opiates
* Intake of antibiotics or probiotics in the past 3 months
* Intake of medications that might interfere with the study outcomes (e.g. bisphosphonates, steroids, calcitonin, thiazides, glucocorticoids)
* Subjects with hypogonadism, hyperparathyroidism or acute or chronic inflammatory diseases including inflammatory bowel disease, infectious diseases, viral infection, cancer, transplant, renal disorders
* Limited mobility
* Self-reported cognitive dysfunction
* Have heart pacemaker
* People with Type 1 diabetes and Type 2 diabetes taking insulin

Primary outcomes:
measure: Fecal samples (bacterial diversity)
timeFrame: Baseline and at 3 months
measure: Fecal samples (transcriptomics)
timeFrame: Baseline and at 3 months
measure: Serum Glucagon-like peptide-1 (GLP-1)
timeFrame: Baseline and at 3 months
measure: Serum Interleukin-1beta (IL-1beta)
timeFrame: Baseline and at 3 months
measure: Serum Noradrenaline/Norepinephrine
timeFrame: Baseline and at 3 months
measure: Serum Vitamin D
timeFrame: Baseline and at 3 months
measure: Serum Total Cholesterol
timeFrame: Baseline and at 3 months
measure: gut quality of life questionnaire
timeFrame: Baseline and at 3 months
measure: Serum Peptide YY (PYY)
timeFrame: Baseline and at 3 months
measure: Serum Ghrelin
timeFrame: Baseline and at 3 months
measure: Serum Leptin
timeFrame: Baseline and at 3 months
measure: Serum Insulin
timeFrame: Baseline and at 3 months
measure: Serum Glucagon
timeFrame: Baseline and at 3 months
measure: Serum Tumor Necrosis Factor Alpha (TNF-α)
timeFrame: Baseline and at 3 months
measure: Serum Interferon gamma (IFNG or IFN-γ)
timeFrame: Baseline and at 3 months
measure: Serum Interleukin-6 (IL-6)
timeFrame: Baseline and at 3 months
measure: Serum Interleukin-1 receptor (IL-1R)
timeFrame: Baseline and at 3 months
measure: Serum Interleukin-10 (IL-10)
timeFrame: Baseline and at 3 months
measure: Serum Dopamine
timeFrame: Baseline and at 3 months
measure: Serum Serotonin
timeFrame: Baseline and at 3 months
measure: Serum Brain-derived neurotrophic factor (BDNF)
timeFrame: Baseline and at 3 months
measure: Serum Precursor proneurotrophin isoform of BDNF (pro-BDNF)
timeFrame: Baseline and at 3 months
measure: Serum Cortisol
timeFrame: Baseline and at 3 months
measure: Serum Insulin-like growth factor-1 (IGF-1)
timeFrame: Baseline and at 3 months
measure: Serum LDL cholesterol
timeFrame: Baseline and at 3 months
measure: Serum Triglycerides
timeFrame: Baseline and at 3 months
measure: Serum Glucose
timeFrame: Baseline and at 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Lubbock
country: United States
facility: Shannon Galyean
state: Texas
Study officials:
affiliation: Texas Tech Nutritional Sciences
name: Shannon Galyean
role: PRINCIPAL_INVESTIGATOR
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