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

Impact of a Prebiotic Supplement on Microbiome, Immune System, and Metabolic Status of Older Adults

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Microbiome; Immune Function
• Intervention / Treatment: Dietary supplement: Placebo; Dietary supplement: Prebiotic supplement

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.

• Study Type: Interventional
• Enrollment (Actual): 98
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune status and function	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.	Baseline and 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Microbiota composition	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.	Baseline and 6 weeks
Microbiota function	Change from baseline in composite of short-chain fatty acids (SCFA) concentration (ug/g stool: acetate + propionate + butyrate) at 6 weeks.	Baseline and 6 weeks
Weight	Change from Baseline in weight at 6 weeks.	Baseline and 6 weeks
Waist Circumference	Change from Baseline in waist circumference at 6 weeks.	Baseline and 6 weeks
Blood pressure	Change from Baseline in blood pressure at 6 weeks.	Baseline and 6 weeks
Total Cholesterol	Change from Baseline in total cholesterol at 6 weeks.	Baseline and 6 weeks
Triglycerides	Change from Baseline in triglycerides at 6 weeks.	Baseline and 6 weeks
HDL-cholesterol	Change from Baseline in HDL-cholesterol at 6 weeks.	Baseline and 6 weeks
Fasting Glucose	Change from Baseline in fasting glucose at 6 weeks.	Baseline and 6 weeks
Fasting Insulin	Change from Baseline in fasting insulin at 6 weeks.	Baseline and 6 weeks

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: Abbott
• Investigators: Principal Investigator: Justin Sonnenburg, PhD, Stanford University

Publications and helpful links

Helpful Links

• Study description

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2019
• Primary Completion (Actual): November 13, 2020
• Study Completion (Actual): December 14, 2020

Study Registration Dates

• First Submitted: September 17, 2018
• First Submitted That Met QC Criteria: September 28, 2018
• First Posted (Actual): October 1, 2018

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 47252

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