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Impact of Diet on the Gut-Muscle Axis in Older Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05549622
Recruitment Status : Not yet recruiting
First Posted : September 22, 2022
Last Update Posted : September 23, 2022
Sponsor:
Information provided by (Responsible Party):
Michael Lustgarten, PhD, Tufts University

Brief Summary:
Muscle health declines during aging. One factor that may impact muscle health is the community of bacteria that live in our intestines, but studies aimed at improving muscle health by targeting the gut in older adults are sparse. The primary goal of this study is to use a diet that is enriched in soluble fiber, which is exclusively utilized by gut bacteria to make substances that can impact muscle health, to improve muscle-related measures in older adults.

Condition or disease Intervention/treatment Phase
Sarcopenia Dietary Exposure Microbial Colonization Other: Low-soluble fiber diet Other: High-soluble fiber diet Not Applicable

Detailed Description:

During aging, skeletal muscle mass and physical function decrease, whereas levels of lipids and adipocytes increase within and between muscle cells, thereby worsening muscle composition. As a result of these age-related changes, older adults are at a higher risk for frailty, falls and fracture, disability and hospitalization, and all-cause mortality. Accordingly, elucidation of mechanisms that underlie muscle mass, muscle composition, and physical function, and interventions that positively affect these variables will be important for addressing the public health priority of an improved quality of life and healthy aging in older adults.

The gut microbiome and its metabolic products are involved in mechanisms that impact skeletal muscle mass, muscle composition, and physical function, which has been defined as the gut-muscle axis. For example, muscle mass and physical function are reduced in animals that do not have a microbiome (germ-free mice), and in antibiotic-treated mice, an intervention that reduces gut bacterial content. Investigating further, gut bacteria-derived metabolites affect muscle mass, muscle composition, and physical function in young and aged animals, including positive effects for the short-chain fatty acids (SCFAs) acetate, propionate, and butyrate, and negative effects for indoxyl sulfate (IS) and para-cresol sulfate (PCS). Similarly, phenol sulfate (PS) and phenylacetylglutamine (PAG) are gut microbiome-derived metabolites that were associated with poor muscle composition and worse physical function in studies of older adult humans that were published by our group. Interestingly, higher colonic levels of SCFAs are associated with a lower pH, an important finding because growth of Enterobacteriaceae, a bacterial family that contains genes involved in the production of IS, PCS, PS, and PAG, is limited in an acidic environment and following exposure to physiological levels of SCFAs. Taken together, these data suggest that interventions aimed at increasing bacterial SCFA production may be an important approach for improving muscle-related measures in older adults.

Soluble fiber fermentation by gut bacteria results in the formation of acetate, propionate, and butyrate, and fecal SCFAs proportionally increase, whereas circulating levels of IS and PCS are reduced in response to high-soluble fiber diets. As a proof of concept, fecal and circulating levels of SCFAs, muscle mass, and aerobic exercise capacity were increased in young mice that were fed a relatively higher soluble fiber diet, but few studies have attempted this approach in older adult humans. When considering that fecal levels of SCFAs decrease during aging, whereas plasma levels of IS, PCS, PS, and PAG increase, these data collectively suggest that a high-soluble fiber diet may be an important approach for improving muscle-related measures in older adults humans. To test this hypothesis, older adults will be randomized to consume a high- or low-soluble fiber diet for 12-weeks.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: 24 older adults (> 65y) will be randomized to consume a high- or low-soluble fiber diet
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of a High-Soluble Fiber Diet on the Gut-Muscle Axis in Older Adults
Estimated Study Start Date : September 15, 2022
Estimated Primary Completion Date : April 15, 2025
Estimated Study Completion Date : April 15, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dietary Fiber

Arm Intervention/treatment
Low-soluble fiber diet Other: Low-soluble fiber diet
12 older adults (>65y) will be randomized to consume the USDA Guidelines for fiber intake (10g of total fiber/1000 calories), as the low-soluble fiber diet

Active Comparator: High-soluble fiber diet Other: High-soluble fiber diet
12 older adults (>65y) will be randomized to consume 34-35g of total fiber/1000 calories, as the high-soluble fiber diet




Primary Outcome Measures :
  1. Quantification of SCFAs in fecal samples [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Fecal levels of bacterial metabolites, including acetate, propionate, and butyrate will be determined at the baseline and week-13 study visits

  2. Quantification of whole-body lean mass with DXA [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Measurement of whole-body lean mass will be determined at the baseline and week-13 study visits

  3. Quantification of hand grip strength [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Grip strength will be determined at the baseline and week-13 study visits

  4. Chair stand test [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    The number of chair stands that can be performed in 30 seconds will be determined at the baseline and week-13 study visits


Secondary Outcome Measures :
  1. Quantification of thigh muscle composition with computed tomography [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Determined at the baseline and week-13 study visits

  2. 6-minute walk test [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    The distance walked in 6 minutes will be determined at the baseline and week-13 study visits

  3. Quantification of gut bacterial metabolites in plasma [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Bacterial metabolites, including SCFAs but also indoxyl sulfate, p-cresol sulfate, phenol sulfate, and phenylacetylglutamine will be determined at the baseline and week-13 study visits

  4. Quantification of gut bacterial composition in fecal samples [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Determined at the baseline and week-13 study visits

  5. Quantification of pH in fecal samples [ Time Frame: Change from baseline when compared with the Week-13 visit ]
    Determined at the baseline and week-13 study visits



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Independently living older adults (> 65y)
  2. Sedentary (Godin-Shepard Leisure Time Physical Activity Questionnaire score < 10)
  3. Non-smoking
  4. Not already consuming a high-fiber diet (> 22, 28 g/day for women, men)
  5. Free of gastrointestinal disease (gastrointestinal cancer, inflammatory bowel disease, bariatric surgery, irritable bowel syndrome)
  6. Fluent in English
  7. Willing to attend three study visits (enrollment, baseline, and week-13)
  8. Willing to consume an abundance of fruits, vegetables, nuts/seeds
  9. Willing to consume an abundance of soluble fiber-rich foods (broccoli, brussels sprouts, flaxseeds sweetened with dates, lima beans, butternut squash, carrots, collard greens)
  10. Willing to tolerate mild gastrointestinal discomfort (bloating, belly grumbling, flatulence). Note that all attempts will be made to replace foods that may trigger these issues.
  11. Willing to not consume antibiotics during the 13-week study
  12. Willing to not schedule a colonoscopy during the 13-week study

Exclusion Criteria:

  1. Unwilling to visit the Tufts Human Nutrition Research Center on Aging (HNRCA) 3x/week to pick up the pre-prepared study diet
  2. Unwilling to only consume the provided food (unsweetened tea and/or black coffee are allowed)
  3. Food allergies related to foods that are included in the study
  4. Chewing problems
  5. Unwilling to wear a daily step counter (pedometer)
  6. Unwilling to complete a daily questionnaire that will assess gastrointestinal comfort
  7. Malnutrition (BMI < 18.5 kg/m2)
  8. Use of supplemental probiotics or antibiotics, participation in an investigational drug evaluation, or a recent change in habitual medication use within the 1 month-period prior to the screening visit
  9. > 5% weight loss or weight gain within the past 6-months
  10. A recent history of alcohol abuse (within the past 5 years)
  11. A history of any significant injury or surgery that currently affects physical functioning and ability to perform physical function testing
  12. Treatment with immunosuppressive drugs
  13. A prior diagnosis of organ failure (heart, liver, renal, respiratory)
  14. Diabetes mellitus (type 1, or type 2 with insulin therapy)
  15. Chronic kidney disease (eGFR ≤ 30 mL/min/1.73 m2)
  16. Overt disease (cancer, dementia, cardiovascular disease)
  17. Chronic use of anti-inflammatory medication (corticosteroids)
  18. Already enrolled in another research study
  19. Active infection, including Tuberculosis , HIV, malaria, hepatitis, shingles, Methicillin-Resistant Staphylococcus Aureus (MRSA), SARS-CoV-2
  20. Any major illness or condition that may interfere with study outcomes at the discretion of the study physician
  21. Won't remain in Boston for the 13-week study duration
  22. Unwilling to complete a daily checklist aimed at quantifying the amount of food eaten on the study diet

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05549622


Contacts
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Contact: Michael S Lustgarten, PhD 646 600 0124 michael.lustgarten@tufts.edu

Sponsors and Collaborators
Tufts University
Investigators
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Study Director: Michael S Lustgarten, PhD Scientist II, NEPS Laboratory
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Responsible Party: Michael Lustgarten, PhD, Principal Investigator, Tufts University
ClinicalTrials.gov Identifier: NCT05549622    
Other Study ID Numbers: GRANT13386865
First Posted: September 22, 2022    Key Record Dates
Last Update Posted: September 23, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No data from participants will be shared with researchers not affiliated with this project.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Michael Lustgarten, PhD, Tufts University:
skeletal muscle
soluble fiber
gut-muscle axis
microbiome
SCFA
Uremic metabolites
Additional relevant MeSH terms:
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Communicable Diseases
Infections
Sarcopenia
Muscular Atrophy
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Atrophy
Pathological Conditions, Anatomical
Disease Attributes
Pathologic Processes