The RAMP Study - Rejuvenation of the Aging Microbiota With Prebiotics

Inflammation Clinical Trial

— RAMP  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03690999
• Other study ID #: 47252
• Status: Completed
• Phase: N/A
• Start date: March 14, 2019
• Est. completion date: December 14, 2020

Study information

• Verified date: February 2023
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 98
• Est. completion date: December 14, 2020
• Est. primary completion date: November 13, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Immune Function
• Inflammation
• Microbiome

Intervention

Dietary Supplement:
• Placebo
Placebo product
• Prebiotic supplement
Prebiotic supplement

Locations

Country	Name	City	State
United States	Stanford University	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Abbott

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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: IFNa pSTAT1, pSTAT3, pSTAT5; IL-6 pSTAT1, pSTAT3, pSTAT5; IFN? pSTAT1; IL-21 pSTAT1; In CD4+ T cells: IFNa pSTAT5; IL-6 pSTAT5; In B cells: IFNa pSTAT1; in monocytes: IL-10 pSTAT3; IFN? pSTAT3; IFNa 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	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
Secondary	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
Secondary	Weight	Change from Baseline in weight at 6 weeks.	Baseline and 6 weeks
Secondary	Waist Circumference	Change from Baseline in waist circumference at 6 weeks.	Baseline and 6 weeks
Secondary	Blood pressure	Change from Baseline in blood pressure at 6 weeks.	Baseline and 6 weeks
Secondary	Total Cholesterol	Change from Baseline in total cholesterol at 6 weeks.	Baseline and 6 weeks
Secondary	Triglycerides	Change from Baseline in triglycerides at 6 weeks.	Baseline and 6 weeks
Secondary	HDL-cholesterol	Change from Baseline in HDL-cholesterol at 6 weeks.	Baseline and 6 weeks
Secondary	Fasting Glucose	Change from Baseline in fasting glucose at 6 weeks.	Baseline and 6 weeks
Secondary	Fasting Insulin	Change from Baseline in fasting insulin at 6 weeks.	Baseline and 6 weeks

External Links

•   Study description