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The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters.

Primary Purpose

Metabolic Syndrome, Dyslipidemias, Diabetes Mellitus

Status

Unknown status

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

Glycine

About this trial

This is an interventional prevention trial for Metabolic Syndrome

Eligibility Criteria

40 Years - 65 Years (Adult, Older Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

Male between the ages of 40-65 years old.
Fulfill at least three of the five diagnostic criteria for the Metabolic Syndrome.
To be able to give their written consent to participate in this study.

Exclusion Criteria:

Abnormal Liver function tests ≥ 3 times upper limit of normal (ULN).
Chronic liver disease other than NAFLD.
Previous gastric or small bowel surgery.
Abnormal Thyroid-stimulating hormone (TSH) level.
Known Tobacco Smoking more than 10 cigarettes per day.
Known alcohol consumption more than 2 drink per day.
Use of medications that include: Insulin or Insulin secretagogues, Thiazolidinediones, Glucocorticosteroids, Hormone replacement therapy.
Fever > 38.2 °C in the past 2 weeks.
Autoimmune or Auto-inflammatory disease.
Chronic kidney disease ≥ stage III.
Nephrotic syndrome.
Hemoglobin <12 g/dL.
Metal clips or implants that preclude magnetic resonance imaging.

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Glycine

Arm Description

Glycine total daily dose of 150mg/kg divided three times daily with meals (powder dissolved in 1 cup of water) for 12 weeks.

Outcomes

Primary Outcome Measures

LDL Cholesterol levels

Change in LDL Cholesterol levels

Secondary Outcome Measures

Triglyceride levels

Change in Triglyceride levels

HDL Cholesterol levels

Change in HDL Cholesterol levels

HbA1C levels

Change in Glycated hemoglobin (HbA1C) levels

Full Information

NCT ID

NCT03850314

First Posted

February 19, 2019

Last Updated

February 20, 2019

Sponsor

Prof. Tony hayek MD

1. Study Identification

Unique Protocol Identification Number

NCT03850314

Brief Title

The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters.

Official Title

The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters: A Clinical and Ex-vivo Study.

Study Type

Interventional

2. Study Status

Record Verification Date

February 2019

Overall Recruitment Status

Unknown status

Study Start Date

March 2019 (Anticipated)

Primary Completion Date

December 2019 (Anticipated)

Study Completion Date

June 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Prof. Tony hayek MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

The current study will test the central hypothesis that Glycine supplementation in humans improves Lipid profile and therefore reduces the risk of Atherosclerosis. Secondary outcomes including Insulin sensitivity and parameters related to Metabolic Syndrome (MetS) will also be measured. Furthermore, a mechanistic study in an ex-vivo model will test the hypothesis that Glycine via its key biosynthetic pathway involving Serine Hydroxymethyltransferase 2 (SHMT2), is athero-protective by inhibiting Sterol regulatory element-binding protein 2 (SREBP2)-mediated cholesterol biosynthesis in murine macrophage-like cell line.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome, Dyslipidemias, Diabetes Mellitus, Obesity, Atherosclerosis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2, Phase 3

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Glycine

Arm Type

Experimental

Arm Description

Glycine total daily dose of 150mg/kg divided three times daily with meals (powder dissolved in 1 cup of water) for 12 weeks.

Intervention Type

Dietary Supplement

Intervention Name(s)

Glycine

Intervention Description

Glycine powder to be dissolved in water.

Primary Outcome Measure Information:

Title

LDL Cholesterol levels

Description

Change in LDL Cholesterol levels

Time Frame

12 weeks

Secondary Outcome Measure Information:

Title

Triglyceride levels

Description

Change in Triglyceride levels

Time Frame

12 weeks

Title

HDL Cholesterol levels

Description

Change in HDL Cholesterol levels

Time Frame

12 weeks

Title

HbA1C levels

Description

Change in Glycated hemoglobin (HbA1C) levels

Time Frame

12 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male between the ages of 40-65 years old. Fulfill at least three of the five diagnostic criteria for the Metabolic Syndrome. To be able to give their written consent to participate in this study. Exclusion Criteria: Abnormal Liver function tests ≥ 3 times upper limit of normal (ULN). Chronic liver disease other than NAFLD. Previous gastric or small bowel surgery. Abnormal Thyroid-stimulating hormone (TSH) level. Known Tobacco Smoking more than 10 cigarettes per day. Known alcohol consumption more than 2 drink per day. Use of medications that include: Insulin or Insulin secretagogues, Thiazolidinediones, Glucocorticosteroids, Hormone replacement therapy. Fever > 38.2 °C in the past 2 weeks. Autoimmune or Auto-inflammatory disease. Chronic kidney disease ≥ stage III. Nephrotic syndrome. Hemoglobin <12 g/dL. Metal clips or implants that preclude magnetic resonance imaging.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Tony Hayek, MD

Phone

+972523782009

t_hayek@rmc.gov.il

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Tony Hayek, MD

Organizational Affiliation

Rambam Health Care Campus

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

23995626

Citation

Moore KJ, Sheedy FJ, Fisher EA. Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol. 2013 Oct;13(10):709-21. doi: 10.1038/nri3520. Epub 2013 Sep 2.

Results Reference

background

PubMed Identifier

22064431

Citation

Weber C, Noels H. Atherosclerosis: current pathogenesis and therapeutic options. Nat Med. 2011 Nov 7;17(11):1410-22. doi: 10.1038/nm.2538.

Results Reference

background

PubMed Identifier

24727233

Citation

Michas G, Micha R, Zampelas A. Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle. Atherosclerosis. 2014 Jun;234(2):320-8. doi: 10.1016/j.atherosclerosis.2014.03.013. Epub 2014 Mar 27.

Results Reference

background

PubMed Identifier

28620111

Citation

Sacks FM, Lichtenstein AH, Wu JHY, Appel LJ, Creager MA, Kris-Etherton PM, Miller M, Rimm EB, Rudel LL, Robinson JG, Stone NJ, Van Horn LV; American Heart Association. Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association. Circulation. 2017 Jul 18;136(3):e1-e23. doi: 10.1161/CIR.0000000000000510. Epub 2017 Jun 15. Erratum In: Circulation. 2017 Sep 5;136(10 ):e195.

Results Reference

background

PubMed Identifier

28030455

Citation

Rom O, Aviram M. It is not just lipids: proatherogenic vs. antiatherogenic roles for amino acids in macrophage foam cell formation. Curr Opin Lipidol. 2017 Feb;28(1):85-87. doi: 10.1097/MOL.0000000000000377. No abstract available.

Results Reference

background

PubMed Identifier

20173117

Citation

Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, Dungan J, Newby LK, Hauser ER, Ginsburg GS, Newgard CB, Kraus WE. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010 Apr;3(2):207-14. doi: 10.1161/CIRCGENETICS.109.852814. Epub 2010 Feb 19.

Results Reference

background

PubMed Identifier

22450427

Citation

Wurtz P, Raiko JR, Magnussen CG, Soininen P, Kangas AJ, Tynkkynen T, Thomson R, Laatikainen R, Savolainen MJ, Laurikka J, Kuukasjarvi P, Tarkka M, Karhunen PJ, Jula A, Viikari JS, Kahonen M, Lehtimaki T, Juonala M, Ala-Korpela M, Raitakari OT. High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis. Eur Heart J. 2012 Sep;33(18):2307-16. doi: 10.1093/eurheartj/ehs020. Epub 2012 Mar 26.

Results Reference

background

PubMed Identifier

24401236

Citation

Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, Hauser ER, Newgard CB, Kraus WE, Newby LK, Shah SH. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014 Jan;232(1):191-6. doi: 10.1016/j.atherosclerosis.2013.10.036. Epub 2013 Nov 12.

Results Reference

background

PubMed Identifier

24910999

Citation

Yang R, Dong J, Zhao H, Li H, Guo H, Wang S, Zhang C, Wang S, Wang M, Yu S, Chen W. Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors. PLoS One. 2014 Jun 9;9(6):e99598. doi: 10.1371/journal.pone.0099598. eCollection 2014.

Results Reference

background

PubMed Identifier

26231617

Citation

Yang RY, Wang SM, Sun L, Liu JM, Li HX, Sui XF, Wang M, Xiu HL, Wang S, He Q, Dong J, Chen WX. Association of branched-chain amino acids with coronary artery disease: A matched-pair case-control study. Nutr Metab Cardiovasc Dis. 2015 Oct;25(10):937-42. doi: 10.1016/j.numecd.2015.06.003. Epub 2015 Jun 14.

Results Reference

background

PubMed Identifier

29944113

Citation

Grajeda-Iglesias C, Aviram M. Specific Amino Acids Affect Cardiovascular Diseases and Atherogenesis via Protection against Macrophage Foam Cell Formation: Review Article. Rambam Maimonides Med J. 2018 Jul 30;9(3):e0022. doi: 10.5041/RMMJ.10337.

Results Reference

background

PubMed Identifier

26722126

Citation

Ding Y, Svingen GF, Pedersen ER, Gregory JF, Ueland PM, Tell GS, Nygard OK. Plasma Glycine and Risk of Acute Myocardial Infarction in Patients With Suspected Stable Angina Pectoris. J Am Heart Assoc. 2015 Dec 31;5(1):e002621. doi: 10.1161/JAHA.115.002621.

Results Reference

background

PubMed Identifier

26959710

Citation

Rom O, Aviram M. Endogenous or exogenous antioxidants vs. pro-oxidants in macrophage atherogenicity. Curr Opin Lipidol. 2016 Apr;27(2):204-6. doi: 10.1097/MOL.0000000000000287. No abstract available.

Results Reference

background

PubMed Identifier

28431321

Citation

Rom O, Grajeda-Iglesias C, Najjar M, Abu-Saleh N, Volkova N, Dar DE, Hayek T, Aviram M. Atherogenicity of amino acids in the lipid-laden macrophage model system in vitro and in atherosclerotic mice: a key role for triglyceride metabolism. J Nutr Biochem. 2017 Jul;45:24-38. doi: 10.1016/j.jnutbio.2017.02.023. Epub 2017 Apr 6.

Results Reference

background

PubMed Identifier

28323968

Citation

Yan-Do R, MacDonald PE. Impaired "Glycine"-mia in Type 2 Diabetes and Potential Mechanisms Contributing to Glucose Homeostasis. Endocrinology. 2017 May 1;158(5):1064-1073. doi: 10.1210/en.2017-00148.

Results Reference

background

PubMed Identifier

25586045

Citation

Yamakado M, Tanaka T, Nagao K, Ishizaka Y, Mitushima T, Tani M, Toda A, Toda E, Okada M, Miyano H, Yamamoto H. Plasma amino acid profile is associated with visceral fat accumulation in obese Japanese subjects. Clin Obes. 2012 Feb;2(1-2):29-40. doi: 10.1111/j.1758-8111.2012.00039.x. Epub 2012 May 22.

Results Reference

background

PubMed Identifier

28802074

Citation

Gaggini M, Carli F, Rosso C, Buzzigoli E, Marietti M, Della Latta V, Ciociaro D, Abate ML, Gambino R, Cassader M, Bugianesi E, Gastaldelli A. Altered amino acid concentrations in NAFLD: Impact of obesity and insulin resistance. Hepatology. 2018 Jan;67(1):145-158. doi: 10.1002/hep.29465. Epub 2017 Nov 17.

Results Reference

background

PubMed Identifier

28684082

Citation

Mirmiran P, Bahadoran Z, Ghasemi A, Azizi F. Contribution of dietary amino acids composition to incidence of cardiovascular outcomes: A prospective population-based study. Nutr Metab Cardiovasc Dis. 2017 Jul;27(7):633-641. doi: 10.1016/j.numecd.2017.05.003. Epub 2017 May 15.

Results Reference

background

PubMed Identifier

22044190

Citation

Petrat F, Boengler K, Schulz R, de Groot H. Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia-reperfusion injury: current knowledge. Br J Pharmacol. 2012 Apr;165(7):2059-72. doi: 10.1111/j.1476-5381.2011.01711.x.

Results Reference

background

PubMed Identifier

28337245

Citation

Razak MA, Begum PS, Viswanath B, Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med Cell Longev. 2017;2017:1716701. doi: 10.1155/2017/1716701. Epub 2017 Mar 1. Erratum In: Oxid Med Cell Longev. 2022 Feb 23;2022:9857645.

Results Reference

background

PubMed Identifier

19232835

Citation

McCarty MF, Barroso-Aranda J, Contreras F. The hyperpolarizing impact of glycine on endothelial cells may be anti-atherogenic. Med Hypotheses. 2009 Aug;73(2):263-4. doi: 10.1016/j.mehy.2008.12.021. Epub 2009 Feb 18.

Results Reference

background

PubMed Identifier

25332814

Citation

McCarty MF, DiNicolantonio JJ. The cardiometabolic benefits of glycine: Is glycine an 'antidote' to dietary fructose? Open Heart. 2014 May 28;1(1):e000103. doi: 10.1136/openhrt-2014-000103. eCollection 2014. No abstract available.

Results Reference

background

PubMed Identifier

23615880

Citation

Wang W, Wu Z, Dai Z, Yang Y, Wang J, Wu G. Glycine metabolism in animals and humans: implications for nutrition and health. Amino Acids. 2013 Sep;45(3):463-77. doi: 10.1007/s00726-013-1493-1. Epub 2013 Apr 25.

Results Reference

background

PubMed Identifier

29364879

Citation

Morscher RJ, Ducker GS, Li SH, Mayer JA, Gitai Z, Sperl W, Rabinowitz JD. Mitochondrial translation requires folate-dependent tRNA methylation. Nature. 2018 Feb 1;554(7690):128-132. doi: 10.1038/nature25460. Epub 2018 Jan 24.

Results Reference

background

PubMed Identifier

24419221

Citation

Mardinoglu A, Agren R, Kampf C, Asplund A, Uhlen M, Nielsen J. Genome-scale metabolic modelling of hepatocytes reveals serine deficiency in patients with non-alcoholic fatty liver disease. Nat Commun. 2014;5:3083. doi: 10.1038/ncomms4083.

Results Reference

background

PubMed Identifier

11229875

Citation

Kruth HS. Macrophage foam cells and atherosclerosis. Front Biosci. 2001 Mar 1;6:D429-55. doi: 10.2741/kruth.

Results Reference

background

PubMed Identifier

24144057

Citation

Diaz-Flores M, Cruz M, Duran-Reyes G, Munguia-Miranda C, Loza-Rodriguez H, Pulido-Casas E, Torres-Ramirez N, Gaja-Rodriguez O, Kumate J, Baiza-Gutman LA, Hernandez-Saavedra D. Oral supplementation with glycine reduces oxidative stress in patients with metabolic syndrome, improving their systolic blood pressure. Can J Physiol Pharmacol. 2013 Oct;91(10):855-60. doi: 10.1139/cjpp-2012-0341. Epub 2013 Jun 17.

Results Reference

background

PubMed Identifier

9892253

Citation

Heresco-Levy U, Javitt DC, Ermilov M, Mordel C, Silipo G, Lichtenstein M. Efficacy of high-dose glycine in the treatment of enduring negative symptoms of schizophrenia. Arch Gen Psychiatry. 1999 Jan;56(1):29-36. doi: 10.1001/archpsyc.56.1.29.

Results Reference

background

PubMed Identifier

10784481

Citation

Evins AE, Fitzgerald SM, Wine L, Rosselli R, Goff DC. Placebo-controlled trial of glycine added to clozapine in schizophrenia. Am J Psychiatry. 2000 May;157(5):826-8. doi: 10.1176/appi.ajp.157.5.826.

Results Reference

background

PubMed Identifier

28254760

Citation

Mardinoglu A, Bjornson E, Zhang C, Klevstig M, Soderlund S, Stahlman M, Adiels M, Hakkarainen A, Lundbom N, Kilicarslan M, Hallstrom BM, Lundbom J, Verges B, Barrett PH, Watts GF, Serlie MJ, Nielsen J, Uhlen M, Smith U, Marschall HU, Taskinen MR, Boren J. Personal model-assisted identification of NAD+ and glutathione metabolism as intervention target in NAFLD. Mol Syst Biol. 2017 Mar 2;13(3):916. doi: 10.15252/msb.20167422.

Results Reference

background

PubMed Identifier

12485966

Citation

National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002 Dec 17;106(25):3143-421. No abstract available.

Results Reference

background

PubMed Identifier

15161807

Citation

Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004 Jun;27(6):1487-95. doi: 10.2337/diacare.27.6.1487.

Results Reference

background

PubMed Identifier

27312947

Citation

Dulai PS, Sirlin CB, Loomba R. MRI and MRE for non-invasive quantitative assessment of hepatic steatosis and fibrosis in NAFLD and NASH: Clinical trials to clinical practice. J Hepatol. 2016 Nov;65(5):1006-1016. doi: 10.1016/j.jhep.2016.06.005. Epub 2016 Jun 14.

Results Reference

background

PubMed Identifier

22554256

Citation

Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease - MRI accurately quantifies hepatic steatosis in NAFLD. Aliment Pharmacol Ther. 2012 Jul;36(1):22-9. doi: 10.1111/j.1365-2036.2012.05121.x. Epub 2012 May 3.

Results Reference

background

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The Effects of Glycine on Atherosclerosis and Metabolic Syndrome-related Parameters.

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