Glycine Deficiency and the Kinetics of Acylglycine in Morbid Obesity

Study Overview
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Brief Summary
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This study aims to evaluate the effects of oral glycine supplementation on plasma glycine concentration, intracellular glutathione (GSH) concentration, plasma acylglycine concentration, urine acylglycine concentration, and insulin resistance in subjects with morbid obesity. This is an open-labelled trial. 20 adults with morbid obesity will be recruited. Following screening and baseline metabolic evaluations, eligible subjects will be given oral glycine supplements for 14 ± 5 days. Upon completing glycine supplementation, subjects will return for their post-supplement metabolic assessment. The investigators hypothesize that oral glycine supplementation in morbidly obese patients normalizes plasma glycine concentration, increases intracellular GSH concentration, increases plasma and urinary acylglycine concentration, and improves insulin resistance.

Official Title
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Glycine Deficiency and the Kinetics of Acylglycine in Morbid Obesity

Conditions
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Morbid Obesity, Glycine; Metabolic Disorder

Intervention / Treatment
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* Dietary Supplement: Glycine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 21-65 years BMI ≥ 32.5 kg/m2 Able to provide informed consent Able to maintain present diet throughout the study duration Exclusion Criteria: Weight > 150 kg Type 2 Diabetes Mellitus Allergy to soy Ongoing treatment with weight-loss medications (e.g. orlistat, phentermine, liraglutide) Systemic steroid usage (eg. prednisolone, hydrocortisone, cortisone, dexamethasone) 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 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) Cancer within the last 3-years (except squamous cell and basal cell cancer of the skin) Any factors likely to limit adherence to study protocol

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glycine supplementation<br>Glycine supplementation | Dietary Supplement: Glycine<br>* Oral glycine tablets (100 mg/kg/day) in divided doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amino acid concentration | Post-treatment changes amino acid concentration in plasma and red blood cell | 14 days | 
| Acylglycine concentration | Post-treatment changes acylglycine concentration in plasma and urine | 14 days | 
| Acylcarnitine concentration | Post-treatment changes acylcarnitine concentration in plasma and urine | 14 days | 
| Glutathione concentration | Post-treatment changes in glutathione concentration in plasma and red blood cell | 14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin resistance index | Post-treatment changes in insulin resistance index | 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Morbid obesity, Insulin Resistance, Glycine metabolism