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

NCT ID: NCT04660513

Last Updated: 2020-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

42 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-12-08

Study Completion Date

2020-11-04

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Glycine Metabolism Disturbances Insulin Resistance Morbid Obesity Oxidative Stress

Keywords

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glycine obesity bariatric surgery gluthathione

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Morbid obesity

BMI 32.5 kg/m2 and above

Bariatric surgery

Intervention Type PROCEDURE

Subjects with morbid obesity underwent bariatric surgery

Non-obese healthy controls

BMI below 25 kg/m2

No interventions assigned to this group

Interventions

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Bariatric surgery

Subjects with morbid obesity underwent bariatric surgery

Intervention Type PROCEDURE

Eligibility Criteria

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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%
Minimum Eligible Age

21 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke-NUS Graduate Medical School

OTHER

Sponsor Role collaborator

Baylor College of Medicine

OTHER

Sponsor Role collaborator

National University Health System, Singapore

OTHER

Sponsor Role collaborator

Singapore General Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Singapore General Hospital

Singapore, , Singapore

Site Status

Countries

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Singapore

References

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Tan HC, Hsu JW, Tai ES, Chacko S, Kovalik JP, Jahoor F. The impact of obesity-associated glycine deficiency on the elimination of endogenous and exogenous metabolites via the glycine conjugation pathway. Front Endocrinol (Lausanne). 2024 Apr 3;15:1343738. doi: 10.3389/fendo.2024.1343738. eCollection 2024.

Reference Type DERIVED
PMID: 38633754 (View on PubMed)

Tan HC, Hsu JW, Tai ES, Chacko S, Wu V, Lee CF, Kovalik JP, Jahoor F. De Novo Glycine Synthesis Is Reduced in Adults With Morbid Obesity and Increases Following Bariatric Surgery. Front Endocrinol (Lausanne). 2022 Jun 9;13:900343. doi: 10.3389/fendo.2022.900343. eCollection 2022.

Reference Type DERIVED
PMID: 35757406 (View on PubMed)

Other Identifiers

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SGH-ENDO-GlycineTA-001

Identifier Type: -

Identifier Source: org_study_id