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The RAMP Study - Rejuvenation of the Aging Microbiota With Prebiotics (RAMP)

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ClinicalTrials.gov Identifier: NCT03690999
Recruitment Status : Completed
First Posted : October 1, 2018
Last Update Posted : July 6, 2021
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
Justin L. Sonnenburg, Stanford University

Brief Summary:
An individual's immune and metabolic status is coupled to consumed carbohydrates. Complex carbohydrates that are not digested by human enzymes may influence host biology by impacting microbiota composition and function, or act in a yet-unknown microbiota-independent manner. Prebiotics offer a promising safe route to influence host health, possibly via the microbiota. However, it remains largely unknown to what extent immune function and metabolism can be modulated by prebiotics.

Condition or disease Intervention/treatment Phase
Microbiome Immune Function Inflammation Dietary Supplement: Placebo Dietary Supplement: Prebiotic supplement Not Applicable

Detailed Description:
The objective of this study is to define the impact of a prebiotic supplement on microbiome, immune system, and metabolic status in older adults. This study will determine the degree to which a prebiotic supplement can 1) regulate immune status and function including reducing chronic, systemic inflammation as assessed by high dimensional immune profiling, 2) alter microbiota composition and function, 3) impact the microbiota metabolites-potential normalizers of metabolic and immune dysfunction, and 4) alter metabolic markers.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Impact of a Prebiotic Supplement on Microbiome, Immune System, and Metabolic Status of Older Adults
Actual Study Start Date : March 14, 2019
Actual Primary Completion Date : November 13, 2020
Actual Study Completion Date : December 14, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Placebo group
Placebo product
Dietary Supplement: Placebo
Placebo product

Experimental: Prebiotic Supplement, low dose Dietary Supplement: Prebiotic supplement
Prebiotic supplement

Experimental: Prebiotic Supplement, high dose Dietary Supplement: Prebiotic supplement
Prebiotic supplement




Primary Outcome Measures :
  1. Immune status and function [ Time Frame: Baseline and 6 weeks ]
    Change from baseline in Cytokine Response Score (CRS) at 6 weeks. The CRS is a single composite measure of cell-type specific activation of signaling pathways from ex vivo cytokine stimulation of blood samples. This provides a measure of immune response capacity which may be an indicator of immune fitness. The CRS will be calculated as described in Shen-Orr et al, Cell Systems, 2016. The CRS is the sum of 15 age-associated normalized cytokine responses identified in Shen-Orr et. al: In CD8+ T cells: IFNα pSTAT1, pSTAT3, pSTAT5; IL-6 pSTAT1, pSTAT3, pSTAT5; IFNγ pSTAT1; IL-21 pSTAT1; In CD4+ T cells: IFNα pSTAT5; IL-6 pSTAT5; In B cells: IFNα pSTAT1; in monocytes: IL-10 pSTAT3; IFNγ pSTAT3; IFNα pSTAT3; IL-6 pSTAT3. Each feature is calculated as the fold change of the protein in the stimulated condition relative to its level in the unstimulated condition. That value is then normalized to the feature's range: normalized = (x - xmin)/xmax. The 15 normalized values are summed for the CRS.


Secondary Outcome Measures :
  1. Microbiota composition [ Time Frame: Baseline and 6 weeks ]
    Change from baseline in alpha diversity at 6 weeks. We will be using number of observed sequence variants ("species") determined by standard 16S rRNA amplicon sequencing (V3-V5 region followed by DADA2 to define error-corrected sequence variants) as our primary metric of alpha diversity. Higher alpha diversity is better. The units are the # of sequence variants.

  2. Microbiota function [ Time Frame: Baseline and 6 weeks ]
    Change from baseline in composite of short-chain fatty acids (SCFA) concentration (ug/g stool: acetate + propionate + butyrate) at 6 weeks.

  3. Weight [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in weight at 6 weeks.

  4. Waist Circumference [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in waist circumference at 6 weeks.

  5. Blood pressure [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in blood pressure at 6 weeks.

  6. Total Cholesterol [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in total cholesterol at 6 weeks.

  7. Triglycerides [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in triglycerides at 6 weeks.

  8. HDL-cholesterol [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in HDL-cholesterol at 6 weeks.

  9. Fasting Glucose [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in fasting glucose at 6 weeks.

  10. Fasting Insulin [ Time Frame: Baseline and 6 weeks ]
    Change from Baseline in fasting insulin at 6 weeks.



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 60 years old and older
  • Otherwise, healthy subjects willing and able to provide blood as well as stool specimens
  • Must be able to provide signed and dated informed consent and be willing to follow protocol

Exclusion Criteria:

  • Body Mass Index >= 40
  • LDL-C > 190 mg/dL
  • Systolic Blood Pressure >160 mmHg OR Diastolic Blood Pressure > 90 mmHg
  • Use of any of the following drugs/supplements within the last 2 months:

    • systemic antibiotics, antifungals, antivirals or antiparasitics (intravenous, intramuscular, or oral);
    • corticosteroids (intravenous, intramuscular, oral, nasal or inhaled)
    • cytokines
    • methotrexate or immunosuppressive cytotoxic agents
    • metformin
    • proton pump inhibitors (PPIs)
  • Regular use of any of the following medications:

    • regular dose aspirin (>81mg/day)
    • opiate pain medication
  • Use of large doses of commercial probiotics consumed (greater than or equal to 10-8 cfu or organisms per day) - includes tablets, capsules, lozenges, chewing gum or powders in which probiotic is a primary component. Ordinary dietary components such as fermented beverages/milks, yogurts, foods do not apply.
  • Acute disease at the time of enrollment. Acute disease is defined as the presence of a moderate or severe illness with or without fever. Examples include flu or gastroenteritis. Defer sampling until subject recover.
  • Chronic, clinically significant, unstable (unresolved, requiring on-going changes to medical management or medication) pulmonary, cardiovascular, gastrointestinal, hepatic or renal functional abnormality, as determined by medical history. Type 2 diabetes, type 1 diabetes, and dialysis will be excluded.
  • History of active uncontrolled gastrointestinal disorders or diseases including:

    • inflammatory bowel disease (IBD) including ulcerative colitis (mild-moderate-severe), Crohn's disease (mild-moderate-severe), or indeterminate colitis;
    • irritable bowel syndrome (IBS) (moderate-severe);
    • persistent, infectious gastroenteritis, colitis or gastritis, persistent or chronic diarrhea of unknown etiology, Clostridium difficile infection (recurrent) or Helicobacter pylori infection (untreated).
  • History of active cancer in the past 3 years except for squamous or basal cell carcinomas of the skin that have been medically managed by local excision.
  • Unstable dietary history as defined by major changes in diet during the previous month, where the subject has eliminated or significantly increased a major food group in the diet.
  • Recent history of chronic excessive alcohol consumption defined as more than five 1.5-ounce servings of 80 proof distilled spirits, five 12-ounce servings of beer or five 5-ounce servings of wine per day; or > 14 drinks/week.
  • Positive test for HIV, HBV or HCV.
  • Any confirmed or suspected condition/state of immunosuppression or immunodeficiency (primary or acquired) including HIV infection.
  • Surgery of the GI tract, with the exception of cholecystectomy and appendectomy, in the past five years. Any major bowel resection at any time.
  • Regular/frequent use of smoking or chewing tobacco, e-cigarettes, cigars or other nicotine-containing products.
  • Any confirmed or suspected autoimmune disease. Examples include multiple sclerosis and Graves disease.
  • Veganism.
  • Dairy allergies.

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): NCT03690999


Locations
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United States, California
Stanford University
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Abbott
Investigators
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Principal Investigator: Justin Sonnenburg, PhD Stanford University
  Study Documents (Full-Text)

Documents provided by Justin L. Sonnenburg, Stanford University:
Statistical Analysis Plan  [PDF] June 25, 2021

Additional Information:
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Responsible Party: Justin L. Sonnenburg, Associate Professor of Microbiology and Immunology, Stanford University
ClinicalTrials.gov Identifier: NCT03690999    
Other Study ID Numbers: 47252
First Posted: October 1, 2018    Key Record Dates
Last Update Posted: July 6, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Inflammation
Pathologic Processes