Composition & Function of Sarcoplasmic Reticulum in Persons With the Metabolic Syndrome (COMP-SR)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by Washington University School of Medicine
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT02122666
First received: April 22, 2014
Last updated: April 24, 2014
Last verified: April 2014
  Purpose

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".


Condition Intervention
Metabolic Syndrome
Procedure: muscle biopsy

Study Type: Observational
Study Design: Observational Model: Case Control
Time Perspective: Prospective
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

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • Sarcoplasmic Reticulum Composition [ Time Frame: Study Visit Week 4 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Insulin Sensitivity [ Time Frame: Study visit week 4 ] [ Designated as safety issue: No ]
    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.

  • Lean and Fat Body Mass [ Time Frame: Study Visit week 4 ] [ Designated as safety issue: No ]
    We will perform a Duel Energy X-ray absorptiometry (DEXA) scan to approximate lean and fat body mass of study subjects.


Biospecimen Retention:   Samples With DNA

whole blood and frozen tissue


Estimated Enrollment: 100
Study Start Date: March 2014
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
Metabolic Syndrome
Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass
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).
Control
Muscle biopsy to determine sarcoplasmic reticulum composition and function, Oral Glucose tolerance test with insulin levels at time points to determine Insulin sensitivity, DEXA scan to determine lean muscle and fat mass
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).

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

primary care clinic, community sample

Criteria

Control subjects

Inclusion:

  • <15 min exercise per day, <2 days per week
  • Age >18 and <65
  • Body Mass Index (BMI) <25
  • 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

Subjects with the Metabolic Syndrome

Inclusion:

  • <15 min exercise per day, <2 days per week
  • 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 or one standard medication for stage 1 hypertension in men or women (blood pressure 140-159/90-99)
  • Currently Pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02122666

Contacts
Contact: Dustin Higgins, D.O. 314-747-0070 dhiggins@dom.wustl.edu
Contact: Stacy Hurst, R.N. 314-747-3294 shurst@dom.wustl.edu

Locations
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Dustin Higgins, D.O.    314-747-0070    dhiggins@dom.wustl.edu   
Contact: Stacy Hurst, R.N.    314-747-3294    shurst@dom.wustl.edu   
Principal Investigator: Clay F. Semenkovich, M.D.         
Sub-Investigator: Janet B. McGill, M.D.         
Sub-Investigator: Dustin Higgins, D.O.         
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Clay F. Semenkovich, M.D. Washington University School of Medicine
  More Information

Additional Information:
Publications:
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].

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT02122666     History of Changes
Other Study ID Numbers: 201311988
Study First Received: April 22, 2014
Last Updated: April 24, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Washington University School of Medicine:
Metabolic Syndrome
Pre-diabetes
impaired glucose tolerance
Phospholipids

Additional relevant MeSH terms:
Metabolic Syndrome X
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 24, 2014