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

Insulin Resistance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04660513
• Other study ID #: SGH-ENDO-GlycineTA-001
• Status: Completed
• Start date: December 8, 2018
• Est. completion date: November 4, 2020

Study information

• Verified date: December 2020
• Source: Singapore General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: November 4, 2020
• Est. primary completion date: November 4, 2020
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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%

Related Conditions & MeSH terms

• Glycine Metabolism Disturbances
• Insulin Resistance
• Morbid Obesity
• Obesity
• Obesity, Morbid
• Oxidative Stress

Intervention

Procedure:
• Bariatric surgery
Subjects with morbid obesity underwent bariatric surgery

Locations

Country	Name	City	State
Singapore	Singapore General Hospital	Singapore

Sponsors (4)

Lead Sponsor	Collaborator
Singapore General Hospital	Baylor College of Medicine, Duke-NUS Graduate Medical School, National University Health System, Singapore

Country where clinical trial is conducted

Singapore, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycine kinetic	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
Primary	Insulin sensitivity	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