Gut Microbiomes in Patients With Metabolic Syndrome

Gut Microbiomes and Viromes in Patients With Metabolic Syndrome

Metabolic syndrome (MS) is defined by a manifestation of cardiometabolic risk factors including high blood pressure, glucose and triglycerides, low high-density lipoprotein (HDL) cholesterol, and abdominal obesity. It is closely associated with other diseases such as fatty liver and gouty arthritis. In recent years there is evidence that gut microorganisms are intimately linked to health and wellbeing. Here, the investigators hypothesize that gut microorganisms are involved in the regulation and/or onset of MS and its symptoms.

Study Overview

• Status: Unknown
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Drug: Metformin; Behavioral: lifestyle modification; Drug: Simvastatin 10mg; Drug: Amlodipine 5mg

Detailed Description

There is mounting evidence that the gut microbiome plays a vital role in health and wellbeing. In particular, population-association and mouse model studies have demonstrated that gut bacteria can be reproducibly linked to obesity and diabetes. There is, however, a lack of progress in translating current scientific knowledge to healthcare practices in part due to the strong influence of biogeography and demography on gut microbiomes. Another major knowledge gap in gut microbiomes is the ecology of gut viruses and their associations with MS despite having intimate relationships with human and bacterial hosts.

In this study, the investigators aim to assess variation in the gut microbiomes of patients with MS with reference to the healthy population in Hong Kong, and to explore gut microorganisms as predictive/diagnostic markers of MS and clinical outcomes associated with medical interventions. This will be achieved through studying microorganisms in the stools of participants. The investigators will use the 16S small subunit ribosomal RNA (16S rRNA) marker gene to create compositional profiles of the gut microbial community in healthy and individuals with MS to identify bacterial populations that are associated with the onset and progression of MS. A subset of samples will be selected for bulk DNA sequencing based on their stool community profiles and/or MS parameters to obtain genomic information of the microorganisms involved.

Participants who undergo intervention as part of their routine medical care for MS will be invited to provide stool samples following intervention. These stools will be used to profile gut microbial communities to investigate whether their compositions undergo changes reflective of medical intervention. Here, the aim is to investigate whether resolution of MS symptoms can be linked to alterations in gut microorganisms, and the hypothesis is that their profiles will more closely resemble healthy individuals following medical intervention.

• Study Type: Observational
• Enrollment (Anticipated): 1000

Contacts and Locations

Study Locations

• Hong Kong
  • Sha Tin, Hong Kong
    • Recruiting
    • Department of Microbiology, Chinese University of Hong Kong
    • Contact: Yun Kit Yeoh; Phone Number: 85235053333; Email: yeohyunkit@cuhk.edu.hk
  • Sha Tin, Hong Kong
    • Recruiting
    • Lek Yuen Health Centre
    • Contact: Martin Wong; Phone Number: 85222528782; Email: wong_martin@cuhk.edu.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Residents of Hong Kong will be invited from health talks, blogs, notices and advertisement through various public media channels, as well as patients referred to the Lek Yuen Health Centre, a university teaching clinic, for suspected or confirmed metabolic syndrome.

Description

Inclusion Criteria:

• Resident of Hong Kong

Exclusion Criteria:

• Major organ system impairment such as heart failure, renal failure, and severe impairment of respiratory function.
• On long-term regular immunosuppressive therapy
• Current or history of malignancy
• Current or history of major gastrointestinal diseases, including inflammatory bowel disease, major gastrointestinal surgery
• On medication for glucose or lipid control, such as metformin and statin

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
No metabolic syndrome; Participants who do not fulfill any of the five criteria for metabolic syndrome defined by the International Diabetes Federation.
Metabolic syndrome- partial; Participants who fulfill one or two of the five criteria for metabolic syndrome defined by the International Diabetes Federation.	Drug: Metformin; Participants with high glucose levels will usually be prescribed Metformin 250 mg three times daily. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Behavioral: lifestyle modification; Participants with metabolic syndrome will be offered advice on modifying their diets and exercise regimes. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Drug: Simvastatin 10mg; Participants with elevated lipid levels will usually be prescribed simvastatin 10 mg at night. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Drug: Amlodipine 5mg; Participants with high blood pressure could be prescribed antihypertensive medicine such as Amlodipine. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.
Metabolic syndrome- full; Participants who fulfill three or more of the five criteria for metabolic syndrome defined by the International Diabetes Federation.	Drug: Metformin; Participants with high glucose levels will usually be prescribed Metformin 250 mg three times daily. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Behavioral: lifestyle modification; Participants with metabolic syndrome will be offered advice on modifying their diets and exercise regimes. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Drug: Simvastatin 10mg; Participants with elevated lipid levels will usually be prescribed simvastatin 10 mg at night. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.; Drug: Amlodipine 5mg; Participants with high blood pressure could be prescribed antihypertensive medicine such as Amlodipine. Can be prescribed to either metabolic syndrome-partial or full groups depending on their metabolic syndrome conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist circumference at four weeks	Waist circumference is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a circumference of ≥90 cm (male) or ≥80 cm (female) is a criteria for metabolic syndrome. The investigators will measure this in participants receiving drug-based treatment before and four weeks after medical intervention, and assess stool microbial community compositions to determine whether any changes in waist circumference can be associated with gut microorganisms.	four weeks in participants receiving drug intervention for metabolic syndrome
Change in baseline systolic and diastolic blood pressure at four weeks	Blood pressure is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a blood pressure reading of ≥130/85 mm Hg (systolic/diastolic pressure) is a criteria for metabolic syndrome. The investigators will measure this in participants receiving drug-based treatment before and four weeks after medical intervention, and assess stool microbial community compositions to determine whether any changes in baseline systolic and diastolic blood pressure can be associated with gut microorganisms.	four weeks in participants receiving drug intervention for metabolic syndrome
Change in blood triglyceride levels at four weeks	Blood triglyceride concentration is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a triglyceride level of ≥1.7 mmol/L is a criteria for metabolic syndrome. The investigators will measure this in participants receiving drug-based treatment before and four weeks after medical intervention, and assess stool microbial community compositions to determine whether any changes in blood triglyceride levels can be associated with gut microorganisms.	four weeks in participants receiving drug intervention for metabolic syndrome
Change in high-density lipoprotein (HDL) cholesterol levels at four weeks	High-density lipoprotein (HDL) cholesterol levels is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a HDL cholesterol level of <1.03 mmol/L (males) or <1.29 mmol/L (females) is a criteria for metabolic syndrome. The investigators will measure this in participants receiving drug-based treatment before and four weeks after medical intervention, and assess stool microbial community compositions to determine whether HDL cholesterol levels can be associated with gut microorganisms.	four weeks in participants receiving drug intervention for metabolic syndrome
Change in fasting blood sugar levels at four weeks	Fasting blood sugar levels is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a fasting blood sugar level of ≥5.6 mmol/L is a criteria for metabolic syndrome. The investigators will measure this in participants receiving drug-based treatment before and four weeks after medical intervention, and assess stool microbial community compositions to determine whether fasting blood sugar levels can be associated with gut microorganisms.	four weeks in participants receiving drug intervention for metabolic syndrome
Change in waist circumference at six months	Waist circumference is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a circumference of ≥90 cm (male) or ≥80 cm (female) is a criteria for metabolic syndrome. The investigators will measure this in all participants with metabolic syndrome six months after their initial visit, and assess stool microbial community compositions to determine whether any changes in waist circumference can be associated with gut microorganisms.	six months in all participants with metabolic syndrome
Change in baseline systolic and diastolic blood pressure at six months	Blood pressure is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a blood pressure reading of ≥130/85 mm Hg (systolic/diastolic pressure) is a criteria for metabolic syndrome. The investigators will measure this in all participants with metabolic syndrome six months after their initial visit, and assess stool microbial community compositions to determine whether any changes in baseline systolic and diastolic blood pressure can be associated with gut microorganisms.	six months in all participants with metabolic syndrome
Change in blood triglyceride levels at six months	Blood triglyceride concentration is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a triglyceride level of ≥1.7 mmol/L is a criteria for metabolic syndrome. The investigators will measure this in all participants with metabolic syndrome six months after their initial visit, and assess stool microbial community compositions to determine whether any changes in blood triglyceride levels can be associated with gut microorganisms.	six months in all participants with metabolic syndrome
Change in high-density lipoprotein (HDL) cholesterol levels at six months	High-density lipoprotein (HDL) cholesterol levels is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a HDL cholesterol level of <1.03 mmol/L (males) or <1.29 mmol/L (females) is a criteria for metabolic syndrome. The investigators will measure this in all participants with metabolic syndrome six months after their initial visit, and assess stool microbial community compositions to determine whether HDL cholesterol levels can be associated with gut microorganisms.	six months in all participants with metabolic syndrome
Change in fasting blood sugar levels at six months	Fasting blood sugar levels is one of the five criteria for classifying metabolic syndrome as defined by the International Diabetes Federation. Specifically, a fasting blood sugar level of ≥5.6 mmol/L is a criteria for metabolic syndrome. The investigators will measure this in all participants with metabolic syndrome six months after their initial visit, and assess stool microbial community compositions to determine whether fasting blood sugar levels can be associated with gut microorganisms.	six months in all participants with metabolic syndrome

Collaborators and Investigators

• Sponsor: Chinese University of Hong Kong
• Investigators: Principal Investigator: Yun Kit Yeoh, Chinese University of Hong Kong

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2017
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 23, 2018
• First Submitted That Met QC Criteria: April 3, 2018
• First Posted (Actual): April 5, 2018

Study Record Updates

• Last Update Posted (Actual): July 23, 2018
• Last Update Submitted That Met QC Criteria: July 20, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: gut microbiome; stool
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Amlodipine; Metformin; Simvastatin
• Other Study ID Numbers: 2017.514

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

IPD Plan Description

Participant data may be shared with researchers within the Faculty of Medicine at the Chinese University of Hong Kong, however, these will likely be limited to the healthy cohort as controls for other gut community surveys or the metabolic syndrome cohort for research into closely related medical conditions such as hypertension.

The investigators will share participant clinical (blood pressure, waist circumference, fasting blood sugar, triglycerides), demography (age, gender, medical history, etc) and gut microbial community composition data within the department where the need arises and appropriate approvals have been obtained.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No