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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04660513
Recruitment Status : Completed
First Posted : December 9, 2020
Last Update Posted : December 9, 2020
Sponsor:
Collaborators:
Duke-NUS Graduate Medical School
Baylor College of Medicine
National University Health System, Singapore
Information provided by (Responsible Party):
Singapore General Hospital

Study Description
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:

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.


Condition or disease Intervention/treatment
Glycine Metabolism Disturbances Insulin Resistance Morbid Obesity Oxidative Stress Procedure: Bariatric surgery

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 Design
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Study Type : Observational
Actual Enrollment : 42 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Obesity-Related Glycine Deficiency: Investigating a Long-standing Metabolic Paradox Using Bedside and Bench Approaches
Actual Study Start Date : December 8, 2018
Actual Primary Completion Date : November 4, 2020
Actual Study Completion Date : November 4, 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Glycine

Groups and Cohorts
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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


Outcome Measures
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Primary Outcome Measures :
  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


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes 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
Criteria

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%

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04660513


Locations
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Singapore
Singapore General Hospital
Singapore, Singapore, 169856
Sponsors and Collaborators
Singapore General Hospital
Duke-NUS Graduate Medical School
Baylor College of Medicine
National University Health System, Singapore
More Information
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Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Singapore General Hospital
ClinicalTrials.gov Identifier: NCT04660513    
Other Study ID Numbers: SGH-ENDO-GlycineTA-001
First Posted: December 9, 2020    Key Record Dates
Last Update Posted: December 9, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Singapore General Hospital:
glycine
obesity
bariatric surgery
gluthathione
Additional relevant MeSH terms:
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Obesity
Insulin Resistance
Obesity, Morbid
Overweight
Overnutrition
 Nutrition Disorders
Body Weight
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases