Skip to main content
OpenTrials
Completed

NCT Number: NCT04660513

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Glycine Metabolism Disturbances Body Weight Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Metabolic Diseases Morbid Obesity Nutrition Disorders Nutritional and Metabolic Diseases Obesity Obesity, Morbid Overnutrition Overweight Oxidative Stress Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

21 year–65 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Singapore General Hospital

Singapore, 169856

About this study

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.

Who can participate

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

All subjects:

  • Weight > 150 kg
  • Renal impairment (estimated creatinine clearance estimated by Cockcroft-Gault Equation < 60 ml/min)
  • Haemoglobin concentration < 10 g/L
  • Serum alanine aminotransferase or aspartate aminotransferase above 2x upper limit of normal
  • Uncontrolled hypertension (BP > 180/110 mmHg)
  • Pregnancy
  • Nursing mothers
  • Significant cardiovascular disease (e.g. acute myocardial infarction, congestive cardiac failure, ischemic heart disease, atrial fibrillation, sick sinus syndrome, supraventricular tachycardia)
  • Previous stroke
  • Uncontrolled thyroid disease
  • Surgery requiring general anaesthesia within 4-weeks before enrolment
  • Psychiatric disorders requiring medication
  • Significant alcohol intake (> 1 unit per day for women and > 2 units per day for men)
  • Subcutaneous insulin injections
  • Systemic steroid usage (eg. prednisolone, hydrocortisone, cortisone, dexamethasone)
  • Cancer within the last 5-years (except squamous cell and basal cell cancer of the skin)
  • 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

  • HbA1C < 9%

Treatment and study plan

bariatric surgery

Procedure

Subjects with morbid obesity underwent bariatric surgery

Primary outcomes

  1. 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

  2. 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

Sponsors and collaborators

Lead sponsor

Singapore General Hospital

Other

Collaborators

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

Registry information

Important dates

Study start
2018
Primary completion
2020
Study completion
2020
First posted
Dec 9, 2020
Registry last updated
Dec 9, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.