Obesity-Related Glycine Deficiency: Investigating a Long-standing Metabolic Paradox Using Bedside and Bench Approaches

December 7, 2020 updated by: Singapore General Hospital

Obesity, in addition to causing abnormal glucose and lipid metabolism, is also associated with altered plasma concentrations of multiple amino acids, including increased levels of branched-chain amino acids and decreased levels of glycine. The mechanisms and consequences of obesity- related glycine deficiency are unknown.

The overall aim of this project is to comprehensively study glycine metabolic pathways in morbid obesity using stable-isotope tracer techniques in human subjects and validating kinetic findings using a cell model of oxidative stress.

This will be a single-centre, observational study. 21 individuals with morbid obesity scheduled for bariatric surgery and 21 non-obese controls will be recruit. They will undergo different study visits and procedures and the human biological materials collected will be analysed for as per aims of the studies. We believe that the glycine metabolic pathways, possibly through the optimization of gluthathione (GSH) synthesis, may provide targets to develop novel therapeutic agents.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Metabolic tracers: 1,2-[13C2]-Glycine, 1,2-[13C2]-Glycine, 2,3,3,-[2H3]-Serine and [2H5]-Phenylalanine will be infused for quantification of various pathways associated with glycine metabolism.

Study Type

Observational

Enrollment (Actual)

42

Contacts and Locations

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

Study Locations

  • Singapore
      • Singapore, Singapore, 169856
        • Singapore General Hospital

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

Ages Eligible for Study

21 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

N/A

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Non-obese controls from our healthy volunteer database will be invited to participate. Obese subjects attending the weight management clinics in the hospital will be referred to the study team by their attending physicians

Description

Inclusion Criteria:

  1. Age: 21-65 years
  2. BMI < 25 kg/m2 for non-obese controls or BMI ≥ 32.5 kg/m2 for obese subjects scheduled for bariatric surgery
  3. Able to provide informed consent

Exclusion Criteria:

All subjects:

  1. Weight > 150 kg
  2. Renal impairment (estimated creatinine clearance estimated by Cockcroft-Gault Equation < 60 ml/min)
  3. Haemoglobin concentration < 10 g/L
  4. Serum alanine aminotransferase or aspartate aminotransferase above 2x upper limit of normal
  5. Uncontrolled hypertension (BP > 180/110 mmHg)
  6. Pregnancy
  7. Nursing mothers
  8. Significant cardiovascular disease (e.g. acute myocardial infarction, congestive cardiac failure, ischemic heart disease, atrial fibrillation, sick sinus syndrome, supraventricular tachycardia)
  9. Previous stroke
  10. Uncontrolled thyroid disease
  11. Surgery requiring general anaesthesia within 4-weeks before enrolment
  12. Psychiatric disorders requiring medication
  13. Significant alcohol intake (> 1 unit per day for women and > 2 units per day for men)
  14. Subcutaneous insulin injections
  15. Systemic steroid usage (eg. prednisolone, hydrocortisone, cortisone, dexamethasone)
  16. Cancer within the last 5-years (except squamous cell and basal cell cancer of the skin)
  17. Any factors likely to limit adherence to study protocol (e.g. dementia; alcohol or substance abuse; history of unreliability in medication taking or appointment keeping; significant concerns about participation in the study from spouse, significant other or family members)

Non-obese controls 1. Known Diabetes Mellitus (diagnosed according to 2014 Ministry of Health Clinical Practice Guidelines for Diabetes Mellitus)

Obese subjects

1. HbA1C < 9%

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

  • Observational Models: Case-Control
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Morbid obesity
BMI 32.5 kg/m2 and above
Procedure: Bariatric surgery
Subjects with morbid obesity underwent bariatric surgery
Non-obese healthy controls
BMI below 25 kg/m2

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Glycine kinetic
Time Frame: Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group
Differences in glycine kinetic measurements between obese subjects and controls, and within obese subjects after bariatric surgery
Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group
Insulin sensitivity
Time Frame: Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group
Differences in insulin sensitivity between obese subjects and controls, and within obese subjects after bariatric surgery
Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group

Collaborators and Investigators

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

Sponsor

Singapore General Hospital

Collaborators

Baylor College of Medicine
National University Health System, Singapore
Duke-NUS Graduate Medical School

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

December 8, 2018

Primary Completion (Actual)

November 4, 2020

Study Completion (Actual)

November 4, 2020

Study Registration Dates

First Submitted

December 1, 2020

First Submitted That Met QC Criteria

December 7, 2020

First Posted (Actual)

December 9, 2020

Study Record Updates

Last Update Posted (Actual)

December 9, 2020

Last Update Submitted That Met QC Criteria

December 7, 2020

Last Verified

December 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGH-ENDO-GlycineTA-001

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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