A Proof-of-concept Study Evaluating the Microbiota-gut-brain Axis

October 17, 2024 updated by: National Taiwan University Hospital

The concept of "Microbiota-gut-brain axis" has long been elucidated. However, only few microbiota-related radionuclide imaging studies have been published. The etiology of physiologic bowel FDG uptake is not fully understood. Some previous studies suggested that bacteria play a role in accumulating FDG and the variability of intestinal FDG activity may rely on a specific type of bacteria in the lumen. It is unclear if FDG transfer from the blood to the bowel lumen through a transcellular or paracellular pathways. The GLUT transporters are known to export glucose from mucosal cells to the blood, but it is doubtful they can also transport in the opposite direction. Therefore, some research speculated the focal or intense FDG uptake might be caused by an increase in intestinal permeability and reflects intestinal barrier impairment.

Gut microbiota compositional changes may affect pathogenesis in patients with Parkinson's disease (PD). A previous hypothesis of PD pointed disease originates in the enteric nervous system and spreads via autonomic neurons to the brain, eventually causing PD. Besides, several studies support the clinical use of Tc-99m TRODAT-1 SPECT in assessing the neurodegenerative status of PD. To date, the correlation between physiologic bowel FDG uptake and dopamine transporter degeneration, as evaluated by either semiquantitative or visual analyses, has never been elucidated.

The objective of this study is to investigate the relationship between the pattern of intestinal FDG activity and Tc-99m TRODAT-1 SPECT images based on the theory of "Microbiota-gut-brain axis".

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The key role of gut microbiota in keeping local and systemic homeostasis is termed the "Microbiota-gut-brain axis", which is a complex bidirectional communication system between the gastrointestinal tract and the brain. The hypothalamic-pituitary adrenal (HPA) axis takes part to this bidirectional communication by releasing corticotrophin-releasing factor (CRF), which facilitates the release of adenocorticotrophin hormone (ACTH) from the pituitary, which enters systemic circulation to lead to the release of cortisol from the adrenal glands. Many reports indicating that this hormonal cascade has a significant role in the adjustment of several functions like gastrointestinal transit, visceral sensation and permeability of the intestinal wall.

The etiology of intestinal FDG uptake without pathologic lesions is not fully understood. Tohihara et al. reported physiologic bowel FDG activity at the delayed phase was more than that at the early phase in dual-time images, and postulated FDG secretion was the major cause of physiologic uptake. Franquet et al. reported that physiologic bowel FDG uptake was inhibited by antibiotics, such as rifaximin. Some studies proposed that a specific type of bacteria in the lumen plays a role in gathering FDG, and it explain individual differences in physiologic bowel FDG activity. Previous studies debated about if FDG transfer from the blood to the bowel lumen through a transcellular or paracellular pathways. The GLUT transporters are known to export glucose from mucosal cells to the blood, but it is doubtful they can also transport in the opposite direction. If bowel FDG uptake is associated to intestinal permeability, FDG is likely to migrate through a paracellular pathway because intestinal permeability is adjusted by paracellular tight junction.

There is strong evidence that microbial strains may generate neuroactive molecules such as neurotransmitters, which may interfere with gut and brain functions. Furthermore, gut microbiota compositional changes may affect pathogenesis in patients with Parkinson's disease (PD). A previous hypothesis of PD pointed disease originates in the enteric nervous system and spreads via autonomic neurons to the brain, eventually causing PD. Besides, several studies support the clinical use of Tc-99m TRODAT-1 SPECT in assessing the neurodegenerative status of PD.

To date, no radionuclide imaging studies for correlation between physiologic bowel FDG uptake and dopamine transporter degeneration have been elucidated. The investigators hope to have insight into pathophysiology of PD by investigating the association between the pattern of intestinal FDG activity and Tc-99m TRODAT-1 SPECT images. In addition, research in this field opens the possibility to use neuroactive molecule-producing probiotics as new potential therapeutic tools for patients with PD.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
100

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Taiwan
      • Douliu, Taiwan
        • Recruiting
        • National Taiwan University Hospital Yunlin Branch
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 80 Parkinson's disease patients over 20 years old (the Unified Parkinson's Disease Rating Scale and Hoehn-Yahr Grading Scale are required to provide clinical staging).
  2. 20 non-Parkinson's disease patients over 20 years old (control group).
  3. Those who are not currently using Metformin, can tolerate fasting for 8 hours, have not used antibiotics within 3 months, and have no obvious intestinal diseases.
  4. Subjects and their families agree to join the trial and agree to undergo fluorine-18 deoxyglucose positron imaging (100 subjects will be paid for by research funds) and phosphonium-99m dopamine transporter scan (20 non-Parkinson's patients will be paid for by research funds) syndrome patients) examination.

Exclusion Criteria:

  1. Unable to accept positron or single photon angiography such as checking for panic disorder and hemodynamic instability.
  2. The possible cancer risk caused by the radiation dose obtained from the experiment cannot be accepted.
  3. Pregnant women or women currently breastfeeding.
  4. There is a lack of recent unified Parkinson's disease rating scale and Hoehn-Yahr grading scale, making it impossible to know the clinical stage.
  5. Those who are currently using Metformin, cannot tolerate fasting for 8 hours, have used antibiotics within 3 months, and have obvious intestinal diseases.
  6. The subjects and their families do not agree to join the trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 18F-FDG PET is used as an imaging marker of gut microbiota composition evaluation in PD patients
We will investigate the correlation between 18F-FDC PET bowel uptake and dopamine transporter changes in patients with PD.
Diagnostic test: F18-FDG, Tc-99m TRODAT-1
In this project, 18F-FDG PET is used as an imaging marker of gut microbiota composition evaluation in PD patients, and the nigrostriatal dopamine system is assessed by Tc-99m TRODAT-1 SPECT.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Physiological parameter (visual score 1-3)
Time Frame: through study completion, an average of 2 years
Intestinal FDG uptake classified by visual analysis
through study completion, an average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Taiwan University Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Yi-Hsien Chou, MD, NTUH Yunlin Branch

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 3, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 30, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 26, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 9, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 21, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 202112226MINC

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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