Glycine Metabolism DisturbancesNCT04660513
Obesity-Related Glycine Deficiency: Investigating a Long-standing Metabolic Paradox Using Bedside and Bench Approaches
An observational study of Glycine Metabolism Disturbances and Insulin Resistance, run by Singapore General Hospital at 1 site in Singapore.
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. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Glycine Metabolism Disturbances, Insulin Resistance, Morbid Obesity
- What is being tested?
- Bariatric surgery
- Type of treatment
- Surgery or procedure
- How many people
- 42 participants
- Where
- 1 siteSingapore
- Study dates
- 8 Dec 2018to 4 Nov 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- Adult, Older adult
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
Who may be able to join
- 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
Who cannot join
- 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)
Show all 21Show fewer
- 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
- 1. HbA1C < 9%
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Being tested
- Bariatric surgery
- Keywords
- glycine, obesity, bariatric surgery, gluthathione
- Medical subject headings
- Insulin Resistance, Obesity, Morbid, Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bariatric surgeryProcedure or surgery
Subjects with morbid obesity underwent bariatric surgery
| Study group | Role | What they receive |
|---|---|---|
| Morbid obesity | BMI 32.5 kg/m2 and above Receives: Procedure: Bariatric surgery | |
| Non-obese healthy controls | BMI below 25 kg/m2 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycine kinetic
Differences in glycine kinetic measurements between obese subjects and controls, and within obese subjects after bariatric surgery
Measured: Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group
Insulin sensitivity
Differences in insulin sensitivity between obese subjects and controls, and within obese subjects after bariatric surgery
Measured: Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2020
- Study start8 Dec 2018
- Primary completion4 Nov 2020
- Study completion4 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Glycine Metabolism DisturbancesStudies of the same condition, open and under way.
- More trials run by Singapore General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Singapore General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Duke-NUS Graduate Medical School, Baylor College of Medicine, National University Health System, Singapore
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04660513
- Sponsor's protocol ID
- SGH-ENDO-GlycineTA-001
- Status last verified
- Dec 2020
- First submitted
- 1 Dec 2020
- Last updated
- 9 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 38633754Tan 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.
PubMed 35757406
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Obesity-Related Glycine Deficiency: Investigating a Long-standing Metabolic Paradox Using Bedside and Bench Approaches
- ClinicalTrials.gov ID
- NCT04660513
- Acronym / sponsor ID
- SGH-ENDO-GlycineTA-001
- Keywords
- glycine, obesity, bariatric surgery, gluthathione
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Singapore General HospitalUniversity, hospital or other
- Collaborators
- Duke-NUS Graduate Medical School, Baylor College of Medicine, National University Health System, Singapore
- Study start
- 8 Dec 2018 (actual)
- Primary completion
- 4 Nov 2020 (actual)
- Study completion
- 4 Nov 2020 (actual)
- First posted
- 9 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morbid obesity | – | Procedure: Bariatric surgeryBMI 32.5 kg/m2 and above |
| Non-obese healthy controls | – | –BMI below 25 kg/m2 |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- 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
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (21 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bariatric surgerySubjects with morbid obesity underwent bariatric surgery | Procedure or surgery | Morbid obesity |
Primary outcome
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Derived from this study: PubMed 38633754Tan 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.
- Derived from this study: PubMed 35757406Tan 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.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Glycine Metabolism Disturbances and Insulin Resistance, run by Singapore General Hospital at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycine kinetic (time frame: Baseline for all subjects and 5-12 months after bariatric surgery for morbid obesity group). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04660513, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Dec 2020.