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

Primary Purpose

Sarcopenia, Dietary Exposure, Microbial Colonization

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Low-soluble fiber diet
High-soluble fiber diet
Sponsored by
Tufts University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcopenia focused on measuring skeletal muscle, soluble fiber, gut-muscle axis, microbiome, SCFA, Uremic metabolites

Eligibility Criteria

65 Years - undefined (Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Jean Mayer Human Nutrition Research Center on Aging at Tufts UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Active Comparator

Arm Label

Low-soluble fiber diet

High-soluble fiber diet

Arm Description

Outcomes

Primary Outcome Measures

Quantification of SCFAs in fecal samples
Fecal levels of bacterial metabolites, including acetate, propionate, and butyrate will be determined at the baseline and week-13 study visits
Quantification of whole-body lean mass with DXA
Measurement of whole-body lean mass will be determined at the baseline and week-13 study visits
Quantification of hand grip strength
Grip strength will be determined at the baseline and week-13 study visits
Chair stand test
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

Quantification of thigh muscle composition with computed tomography
Determined at the baseline and week-13 study visits
6-minute walk test
The distance walked in 6 minutes will be determined at the baseline and week-13 study visits
Quantification of gut bacterial metabolites in plasma
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
Quantification of gut bacterial composition in fecal samples
Determined at the baseline and week-13 study visits
Quantification of pH in fecal samples
Determined at the baseline and week-13 study visits

Full Information

First Posted
August 24, 2022
Last Updated
April 10, 2023
Sponsor
Tufts University
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1. Study Identification

Unique Protocol Identification Number
NCT05549622
Brief Title
Impact of Diet on the Gut-Muscle Axis in Older Adults
Official Title
Impact of a High-Soluble Fiber Diet on the Gut-Muscle Axis in Older Adults
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tufts University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcopenia, Dietary Exposure, Microbial Colonization
Keywords
skeletal muscle, soluble fiber, gut-muscle axis, microbiome, SCFA, Uremic metabolites

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
24 older adults (> 65y) will be randomized to consume a high- or low-soluble fiber diet
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low-soluble fiber diet
Arm Type
Other
Arm Title
High-soluble fiber diet
Arm Type
Active Comparator
Intervention Type
Other
Intervention Name(s)
Low-soluble fiber diet
Intervention Description
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
Intervention Type
Other
Intervention Name(s)
High-soluble fiber diet
Intervention Description
12 older adults (>65y) will be randomized to consume 34-35g of total fiber/1000 calories, as the high-soluble fiber diet
Primary Outcome Measure Information:
Title
Quantification of SCFAs in fecal samples
Description
Fecal levels of bacterial metabolites, including acetate, propionate, and butyrate will be determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Quantification of whole-body lean mass with DXA
Description
Measurement of whole-body lean mass will be determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Quantification of hand grip strength
Description
Grip strength will be determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Chair stand test
Description
The number of chair stands that can be performed in 30 seconds will be determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Secondary Outcome Measure Information:
Title
Quantification of thigh muscle composition with computed tomography
Description
Determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
6-minute walk test
Description
The distance walked in 6 minutes will be determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Quantification of gut bacterial metabolites in plasma
Description
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
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Quantification of gut bacterial composition in fecal samples
Description
Determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit
Title
Quantification of pH in fecal samples
Description
Determined at the baseline and week-13 study visits
Time Frame
Change from baseline when compared with the Week-13 visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Independently living older adults (> 65y) Sedentary (Godin-Shepard Leisure Time Physical Activity Questionnaire score < 10) Non-smoking Not already consuming a high-fiber diet (> 22, 28 g/day for women, men) Free of gastrointestinal disease (gastrointestinal cancer, inflammatory bowel disease, bariatric surgery, irritable bowel syndrome) Fluent in English Willing to attend three study visits (enrollment, baseline, and week-13) Willing to consume an abundance of fruits, vegetables, nuts/seeds Willing to consume an abundance of soluble fiber-rich foods (broccoli, brussels sprouts, flaxseeds sweetened with dates, lima beans, butternut squash, carrots, collard greens) 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. Willing to not consume antibiotics during the 13-week study Willing to not schedule a colonoscopy during the 13-week study Exclusion Criteria: Unwilling to visit the Tufts Human Nutrition Research Center on Aging (HNRCA) 3x/week to pick up the pre-prepared study diet Unwilling to only consume the provided food (unsweetened tea and/or black coffee are allowed) Food allergies related to foods that are included in the study Chewing problems Unwilling to wear a daily step counter (pedometer) Unwilling to complete a daily questionnaire that will assess gastrointestinal comfort Malnutrition (BMI < 18.5 kg/m2) 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 > 5% weight loss or weight gain within the past 6-months A recent history of alcohol abuse (within the past 5 years) A history of any significant injury or surgery that currently affects physical functioning and ability to perform physical function testing Treatment with immunosuppressive drugs A prior diagnosis of organ failure (heart, liver, renal, respiratory) Diabetes mellitus (type 1, or type 2 with insulin therapy) Chronic kidney disease (eGFR ≤ 30 mL/min/1.73 m2) Overt disease (cancer, dementia, cardiovascular disease) Chronic use of anti-inflammatory medication (corticosteroids) Already enrolled in another research study Active infection, including Tuberculosis , HIV, malaria, hepatitis, shingles, Methicillin-Resistant Staphylococcus Aureus (MRSA), SARS-CoV-2 Any major illness or condition that may interfere with study outcomes at the discretion of the study physician Won't remain in Boston for the 13-week study duration Unwilling to complete a daily checklist aimed at quantifying the amount of food eaten on the study diet
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michael S Lustgarten, PhD
Phone
646 600 0124
Email
michael.lustgarten@tufts.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael S Lustgarten, PhD
Organizational Affiliation
Scientist II, NEPS Laboratory
Official's Role
Study Director
Facility Information:
Facility Name
Jean Mayer Human Nutrition Research Center on Aging at Tufts University
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02111
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael S Lustgarten, PhD

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
No data from participants will be shared with researchers not affiliated with this project.

Learn more about this trial

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

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