Role of Gastrointestinal Microbes on Digestion of Resistant Starch and Tryptophan Availability to Humans
1 other identifier
interventional
20
1 country
1
Brief Summary
There is currently a critical gap in knowledge of how intestinal bacterial communities alter metabolic substrates available to the host thereby influencing central and enteric nervous system (CNS/ENS) neurotransmitter levels involved in regulating carbohydrate consumption in humans. Understanding these relationships is essential for developing strategies to improve blood glucose control and to reduce the risk of transitioning from prediabetes to type-2 diabetes (T2D). The investigators' long-term goal is to determine the biological underpinnings of behaviors that impact food intake and blood glucose control that contribute to the development of T2D. The objective of this proposal, which is an essential next step in attaining the investigators' long-term goals, is to determine how bacterial populations in the digestive system impact circulating tryptophan (TRP) and large neutral amino acid (LNAA) levels that regulate production of monoamine 5-hydroxytryptamine (5-HT, serotonin) in the ENS and in gastrointestinal system and the brain. The central hypothesis is that a reduced ratio of TRP producing (TRPp) to TRP consuming (TRPc) bacteria (decreased TRPp:TRPc ratio) in the gut will decrease TRP availability following a carbohydrate meal lowering the plasma TRP:LNAA ratio and resulting in less TRP for ENS/CNS production of 5HT. Further, dietary interventions that promote TRPp bacterial abundance within the gut will increase TRP availability to the host. The investigators will test the central hypothesis and, thereby, accomplish the overall objective for this project by pursuing the following specific aims: 1) Assess impact of divergent microbiota on plasma TRP:LNAA ratio in response to acute carbohydrate consumption, and 2) Assess the impact of dietary supplementation with resistant starch (RS) on gut microbiota and circulating TRP:LNAA ratio. During Aim 1, stool samples will be collected from healthy participants. Participants will be stratified based on gut TRPp:TRPc ratio and the response to an acute meal will be assessed by determining plasma TRP:LNAA ratios. During Aim 2 the capacity for 4-weeks of pre-biotic RS (Potato Starch) supplementation to increase the TRPp:TRPc bacterial ratio in the gut will be determined from stool samples. Additionally, plasma TRP:LNAA ratio following acute carbohydrate consumption before and after supplementation will be determined. The scientific contribution will be to determine the impact of RS on TRPp and TRPc bacteria abundance in the gut, and how bacterial populations impact circulating TRP:LNAA levels, that can impact ENS and CNS 5HT production in humans. This contribution will be significant because it will have direct translational implications for human diseases with altered 5HT signaling.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for early_phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 21, 2016
CompletedFirst Posted
Study publicly available on registry
November 28, 2016
CompletedStudy Start
First participant enrolled
January 1, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2017
CompletedMay 4, 2017
May 1, 2017
11 months
November 21, 2016
May 1, 2017
Conditions
Outcome Measures
Primary Outcomes (2)
Plasma Amino Acid Levels
Baseline
Plasma Amino Acid Levels
Following 4 weeks of supplementation
Secondary Outcomes (1)
Change in Plasma Amino Acid Levels
Baseline vs. 4-weeks
Study Arms (2)
Potato Starch (Bob's Red Mill)
EXPERIMENTALDaily dietary supplementation with Potato Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
Resource ThickenUp Pregelatinized Starch
PLACEBO COMPARATORDaily dietary supplementation with Pregelatinized Starch (48g total/day) suspended in water. 24g will be consumed 2 times per day.
Interventions
Subjects will be assigned to Potato Starch (active) following assessment of their gut microbiome.
Subjects will be assigned to Pregelatinized Starch (placebo) following assessment of their gut microbiome.
Eligibility Criteria
You may qualify if:
- Male and female
- Age 18 - 65 years old
- Non-Obese (BMI ≤ 30 kg/m2 and \>17 kg/m2 )
You may not qualify if:
- Urine toxicology positive,
- Pregnant (female)
- Alcohol intake 48 hours prior to studies,
- Evidence of inherited disorders of lipid metabolism,
- History of Cancer within the last 5 years,
- Human immunodeficiency virus (HIV) antibody positive,
- Patients with solid organ transplants,
- Unstable angina or NY heart association class II failure or above,
- Gastrointestinal disease specifically GI motility disorders,
- Unstable neuropsychiatric disease including major depression/anxiety, eating disorder such as bulimia or anorexia,
- End stage renal or hepatic disease,
- Autoimmune disorders (e.g. SLE),
- Prior bariatric surgery,
- A history or current alcohol/substance abuse or nicotine containing products or illicit drugs of abuse during the preceding 6 months,
- Treatment within one month with sedative hypnotic medications (benzodiazepines, barbiturates), or over the counter sleeping aids
- +5 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Wayne State University
Detroit, Michigan, 48202, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- early phase 1
- Allocation
- NON RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- BASIC SCIENCE
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
November 21, 2016
First Posted
November 28, 2016
Study Start
January 1, 2017
Primary Completion
December 1, 2017
Last Updated
May 4, 2017
Record last verified: 2017-05