Composition & Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome

Metabolic Syndrome Clinical Trial

— COMP-SR  

Official title:

Modulating Physiologic Effects Of Phospholipid Metabolism In Obesity And Diabetes; AIM 4: Composition and Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02122666
• Other study ID #: 201311099
• Status: Active, not recruiting
• Start date: March 2014
• Est. completion date: December 2022

Study information

• Verified date: July 2022
• Source: Washington University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The investigators previous research has suggested that lipid (fatty) composition in the muscle cells of mice plays a key role in their insulin sensitivity. The purpose of this study is to determine whether these specific fat signatures translate to humans by comparing the muscle of healthy patients to those with pre-diabetes, or "the metabolic syndrome".

Description:

The Comp-SR study explores the role of lipid metabolism in key metabolic pathways in skeletal muscle. It is a translation of previous research done in mice studying the effects and functions of certain key enzymes involved in lipid metabolism found to be associated with insulin resistance. These enzymes are fatty acid synthase (FAS), choline/ethanolamine phosphotransferase 1 (CEPT1) and sarcoplasmic-endoplasmic reticulum ATPase (SERCA). Based on the investigators research, it appears that the activity and function of these enzymes determines the ratio of certain phospholipids in the sarcoplasmic reticulum (SR), namely phosphatidylethanolamine (PE) and phosphatidylcholine (PC). Furthermore, the investigators have found that the ratio of these phospholipids correlates with the mouse's sensitivity to insulin.

Based on the muscle biopsies of four healthy persons, it was found that human muscle contains similar phospholipids and phospholipid ratios to mice. It is hypothesized that these phospholipid signatures may be predictive of the metabolic status of humans as well. The specific aims of this study are to determine if the composition and function of the sarcoplasmic reticulum is altered in persons with the metabolic syndrome compared to lean controls. This knowledge could provide new understanding of impediments to effective therapy, novel biomarkers of disease progression, and innovative treatment targets for diabetes.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Control subjects

Inclusion:

Sedentary: No routine exercise, walking <10,000 steps per day Age >18 and <65 Body Mass Index (BMI) <32 Healthy by physical exam (patient is devoid of major acute or chronic illness) No significant abnormality in screening labs

Exclusion:

Currently on any significant prescription medications other than oral contraceptives in women Currently Pregnant Current Tobacco Use

Subjects with the Metabolic Syndrome

Inclusion:

Sedentary: No routine exercise, walking <10,000 steps per day Age >18 and <65 Body Mass Index (BMI) >30

Meet at least three of the following Adult Treatment Panel (ATP) III criteria for the metabolic syndrome:

waist circumference > or = 40 inches in men, > or = 35 inches in women blood triglycerides > or = 150 mg/dL blood HDL cholesterol <40 mg/dL in men, <50 in women blood pressure > or = 130 mmHg systolic, or > or = 85 mmHg diastolic fasting blood sugar > or = 100 mg/dL

Exclusion:

Diagnosed with Type 2 diabetes, coronary artery disease, cancer, liver, lung, or kidney disease or any other major illness

Currently on any significant prescription medications other than:

oral contraceptives in women More than two standard medication for stage 1 hypertension in men or women (blood pressure 140-159/90-99) Currently Pregnant Current Tobacco Use

Related Conditions & MeSH terms

• Metabolic Syndrome
• Syndrome

Intervention

Procedure:
• muscle biopsy
A member of the study team will obtain a small sample of muscle tissue from the patient's thigh (vastus lateralis muscle).

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Washington University School of Medicine

Country where clinical trial is conducted

United States, 

References & Publications (7)

Boulé NG, Haddad E, Kenny GP, Wells GA, Sigal RJ. Effects of exercise on glycemic control and body mass in type 2 diabetes mellitus: a meta-analysis of controlled clinical trials. JAMA. 2001 Sep 12;286(10):1218-27. Review. — View Citation

Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, Singh GM, Gutierrez HR, Lu Y, Bahalim AN, Farzadfar F, Riley LM, Ezzati M; Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Body Mass Index). National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants. Lancet. 2011 Feb 12;377(9765):557-67. doi: 10.1016/S0140-6736(10)62037-5. Epub 2011 Feb 3. — View Citation

Funai K, Song H, Yin L, Lodhi IJ, Wei X, Yoshino J, Coleman T, Semenkovich CF. Muscle lipogenesis balances insulin sensitivity and strength through calcium signaling. J Clin Invest. 2013 Mar;123(3):1229-40. doi: 10.1172/JCI65726. Epub 2013 Feb 8. Erratum in: J Clin Invest. 2013 Aug 1;123(8):3634. — View Citation

Kiens B. Skeletal muscle lipid metabolism in exercise and insulin resistance. Physiol Rev. 2006 Jan;86(1):205-43. Review. — View Citation

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, Alvarado M, Anderson HR, Anderson LM, Andrews KG, Atkinson C, Baddour LM, Barker-Collo S, Bartels DH, Bell ML, Benjamin EJ, Bennett D, Bhalla K, Bikbov B, Bin Abdulhak A, Birbeck G, Blyth F, Bolliger I, Boufous S, Bucello C, Burch M, Burney P, Carapetis J, Chen H, Chou D, Chugh SS, Coffeng LE, Colan SD, Colquhoun S, Colson KE, Condon J, Connor MD, Cooper LT, Corriere M, Cortinovis M, de Vaccaro KC, Couser W, Cowie BC, Criqui MH, Cross M, Dabhadkar KC, Dahodwala N, De Leo D, Degenhardt L, Delossantos A, Denenberg J, Des Jarlais DC, Dharmaratne SD, Dorsey ER, Driscoll T, Duber H, Ebel B, Erwin PJ, Espindola P, Ezzati M, Feigin V, Flaxman AD, Forouzanfar MH, Fowkes FG, Franklin R, Fransen M, Freeman MK, Gabriel SE, Gakidou E, Gaspari F, Gillum RF, Gonzalez-Medina D, Halasa YA, Haring D, Harrison JE, Havmoeller R, Hay RJ, Hoen B, Hotez PJ, Hoy D, Jacobsen KH, James SL, Jasrasaria R, Jayaraman S, Johns N, Karthikeyan G, Kassebaum N, Keren A, Khoo JP, Knowlton LM, Kobusingye O, Koranteng A, Krishnamurthi R, Lipnick M, Lipshultz SE, Ohno SL, Mabweijano J, MacIntyre MF, Mallinger L, March L, Marks GB, Marks R, Matsumori A, Matzopoulos R, Mayosi BM, McAnulty JH, McDermott MM, McGrath J, Mensah GA, Merriman TR, Michaud C, Miller M, Miller TR, Mock C, Mocumbi AO, Mokdad AA, Moran A, Mulholland K, Nair MN, Naldi L, Narayan KM, Nasseri K, Norman P, O'Donnell M, Omer SB, Ortblad K, Osborne R, Ozgediz D, Pahari B, Pandian JD, Rivero AP, Padilla RP, Perez-Ruiz F, Perico N, Phillips D, Pierce K, Pope CA 3rd, Porrini E, Pourmalek F, Raju M, Ranganathan D, Rehm JT, Rein DB, Remuzzi G, Rivara FP, Roberts T, De León FR, Rosenfeld LC, Rushton L, Sacco RL, Salomon JA, Sampson U, Sanman E, Schwebel DC, Segui-Gomez M, Shepard DS, Singh D, Singleton J, Sliwa K, Smith E, Steer A, Taylor JA, Thomas B, Tleyjeh IM, Towbin JA, Truelsen T, Undurraga EA, Venketasubramanian N, Vijayakumar L, Vos T, Wagner GR, Wang M, Wang W, Watt K, Weinstock MA, Weintraub R, Wilkinson JD, Woolf AD, Wulf S, Yeh PH, Yip P, Zabetian A, Zheng ZJ, Lopez AD, Murray CJ, AlMazroa MA, Memish ZA. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012 Dec 15;380(9859):2095-128. doi: 10.1016/S0140-6736(12)61728-0. Erratum in: Lancet. 2013 Feb 23;381(9867):628. AlMazroa, Mohammad A [added]; Memish, Ziad A [added]. — View Citation

McGarry JD. What if Minkowski had been ageusic? An alternative angle on diabetes. Science. 1992 Oct 30;258(5083):766-70. — View Citation

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Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sarcoplasmic Reticulum Composition	We will take a muscle tissue sample from the subject's thigh (vastus lateralis) to quantify phosphatidylcholine to phosphatidylethanolamine ratio of the sarcoplasmic reticulum, as well as SERCA activity and FAS and CEPT1 quantity in the sample.	Study Visit Week 4
Secondary	Insulin Sensitivity	We will perform an oral glucose tolerance test with insulin levels obtained at each time point to determine the Matsuda index, an estimation of insulin sensitivity.	Study visit week 4
Secondary	Lean and Fat Body Mass	We will perform a Duel Energy X-ray absorptiometry (DEXA) scan to approximate lean and fat body mass of study subjects.	Study Visit week 4

External Links

•   Clay F. Semenkovich, MD
•   Washington U in St. Louis, Endocrinology Current Clinical Studies
•   Washington U in St. Louis; Research Participant Registry