Gene Expression Profiles and Metformin Efficacy in Type 2 Diabetes

Type 2 Diabetes Clinical Trial

Official title:

White Blood Cells Gene Expression Profiles as a Tool for Predicting Metformin Efficacy in Patients With Type 2 Diabetes Mellitus

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01334684
• Other study ID #: GExpProMet
• Status: Not yet recruiting
• Phase: N/A
• First received: April 12, 2011
• Last updated: April 12, 2011
• Start date: May 2011
• Est. completion date: September 2013

Study information

• Verified date: February 2011
• Source: Casa Sollievo della Sofferenza IRCCS
• Contact: Salvatore De Cosmo, MD
• Phone: +39088241067
• Email: s.decosmo[@]operapadrepio.it
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Our general aim is to investigate whether messenger RNA (mRNA) and/or microRNA (miRNA) expression profiles in white blood cells, predict metformin monotherapy efficacy in patients with type 2 diabetes.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: September 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 40 Years to 70 Years

Eligibility

Inclusion Criteria:

• Type 2 diabetes (duration of diabetes of at least 2 years)

• age 40-70 yrs

• HbA1c > 6.4 < 9.0

Exclusion Criteria:

• insulin therapy

• contraindications to metformin use

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Metformin
Metformin, pills, 850 mg three times a day for three months

Locations

Country	Name	City	State
Italy	Casa Sollievo Della Sofferenza IRCCS	San Giovanni Rotondo	Foggia

Sponsors (2)

Lead Sponsor	Collaborator
Casa Sollievo della Sofferenza IRCCS	University Hospital, Catania

Country where clinical trial is conducted

Italy, 

References & Publications (11)

Ayers M, Symmans WF, Stec J, Damokosh AI, Clark E, Hess K, Lecocke M, Metivier J, Booser D, Ibrahim N, Valero V, Royce M, Arun B, Whitman G, Ross J, Sneige N, Hortobagyi GN, Pusztai L. Gene expression profiles predict complete pathologic response to neoadjuvant paclitaxel and fluorouracil, doxorubicin, and cyclophosphamide chemotherapy in breast cancer. J Clin Oncol. 2004 Jun 15;22(12):2284-93. Epub 2004 May 10. — View Citation

Bertucci F, Finetti P, Rougemont J, Charafe-Jauffret E, Nasser V, Loriod B, Camerlo J, Tagett R, Tarpin C, Houvenaeghel G, Nguyen C, Maraninchi D, Jacquemier J, Houlgatte R, Birnbaum D, Viens P. Gene expression profiling for molecular characterization of inflammatory breast cancer and prediction of response to chemotherapy. Cancer Res. 2004 Dec 1;64(23):8558-65. — View Citation

Blower PE, Chung JH, Verducci JS, Lin S, Park JK, Dai Z, Liu CG, Schmittgen TD, Reinhold WC, Croce CM, Weinstein JN, Sadee W. MicroRNAs modulate the chemosensitivity of tumor cells. Mol Cancer Ther. 2008 Jan;7(1):1-9. doi: 10.1158/1535-7163.MCT-07-0573. Epub 2008 Jan 9. — View Citation

Camargo A, Ruano J, Fernandez JM, Parnell LD, Jimenez A, Santos-Gonzalez M, Marin C, Perez-Martinez P, Uceda M, Lopez-Miranda J, Perez-Jimenez F. Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil. BMC Genomics. 2010 Apr 20;11:253. doi: 10.1186/1471-2164-11-253. — View Citation

Iwao-Koizumi K, Matoba R, Ueno N, Kim SJ, Ando A, Miyoshi Y, Maeda E, Noguchi S, Kato K. Prediction of docetaxel response in human breast cancer by gene expression profiling. J Clin Oncol. 2005 Jan 20;23(3):422-31. — View Citation

Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B; American Diabetes Association; European Association for Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009 Jan;32(1):193-203. doi: 10.2337/dc08-9025. Epub 2008 Oct 22. — View Citation

Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, Sager PT, Sehnert AJ, Yau M, Kraus WE, Newby LK, Schwartz RS, Voros S, Ellis SG, Tahirkheli N, Waksman R, McPherson J, Lansky A, Winn ME, Schork NJ, Topol EJ; PREDICT (Personalized Risk Evaluation and Diagnosis in the Coronary Tree) Investigators. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann Intern Med. 2010 Oct 5;153(7):425-34. doi: 10.7326/0003-4819-153-7-201010050-00005. — View Citation

Sarasin-Filipowicz M, Krol J, Markiewicz I, Heim MH, Filipowicz W. Decreased levels of microRNA miR-122 in individuals with hepatitis C responding poorly to interferon therapy. Nat Med. 2009 Jan;15(1):31-3. doi: 10.1038/nm.1902. Epub 2009 Jan 4. — View Citation

Wingrove JA, Daniels SE, Sehnert AJ, Tingley W, Elashoff MR, Rosenberg S, Buellesfeld L, Grube E, Newby LK, Ginsburg GS, Kraus WE. Correlation of peripheral-blood gene expression with the extent of coronary artery stenosis. Circ Cardiovasc Genet. 2008 Oct;1(1):31-8. doi: 10.1161/CIRCGENETICS.108.782730. — View Citation

Xia L, Zhang D, Du R, Pan Y, Zhao L, Sun S, Hong L, Liu J, Fan D. miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer. 2008 Jul 15;123(2):372-9. doi: 10.1002/ijc.23501. — View Citation

Yakeu G, Butcher L, Isa S, Webb R, Roberts AW, Thomas AW, Backx K, James PE, Morris K. Low-intensity exercise enhances expression of markers of alternative activation in circulating leukocytes: roles of PPAR? and Th2 cytokines. Atherosclerosis. 2010 Oct;212(2):668-73. doi: 10.1016/j.atherosclerosis.2010.07.002. Epub 2010 Jul 16. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Fasting glucose change after metformin treatment in respect to mRNA and miRNA expression profiles in white blood cells	Changes in fasting glucose levels will be used to evaluate if metformin monotherapy efficacy in type 2 diabetic patients is predicted by mRNA and/or miRNA expression profiles.; Please note that metformin major effect is to decrease hepatic glucose output and, therefore, to lower fasting plasma glucose which is, in fact, the clinical outcome used in this study.; Finally, because of a very short wash-out period (i.e. 5 days) we will not be able to use HbA1c which will be inevitably conditioned by previous oral hypoglicemic therapy.	Baseline and after three months of metfomin therapy	Yes
Secondary	Change in fasting insulin levels after metformin treatment in respect to mRNA and miRNA expression profiles in white blood cells		Baseline and after three months of metfomin therapy	No