Gene Expression Profiles and Metformin Efficacy in Type 2 Diabetes - Full Text View

Purpose

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.

Condition	Intervention
Type 2 Diabetes	Drug: Metformin

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	White Blood Cells Gene Expression Profiles as a Tool for Predicting Metformin Efficacy in Patients With Type 2 Diabetes Mellitus

Resource links provided by NLM:

MedlinePlus related topics: Diabetes Diabetes Medicines Diabetes Type 2

Drug Information available for: Metformin Metformin hydrochloride

U.S. FDA Resources

Further study details as provided by Casa Sollievo della Sofferenza IRCCS:

Primary Outcome Measures:

Fasting glucose change after metformin treatment in respect to mRNA and miRNA expression profiles in white blood cells [ Time Frame: Baseline and after three months of metfomin therapy ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

Change in fasting insulin levels after metformin treatment in respect to mRNA and miRNA expression profiles in white blood cells [ Time Frame: Baseline and after three months of metfomin therapy ] [ Designated as safety issue: No ]

Estimated Enrollment:	100
Study Start Date:	May 2011
Estimated Study Completion Date:	September 2013
Estimated Primary Completion Date:	April 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Metformin At study entry, all oral hypoglycemic agents will be discontinued for 5 days and then metformin (2,550 mg/daily) will be given for 3 months. Fasting plasma glucose will be measured at baseline and 3 months after metformin treatment. Patients will be stratified according to the median value of metformin efficacy as indicated by fasting glucose change after metformin treatment (i.e. baseline fasting glucose minus 3-month fasting glucose). So, two subgroups of patients will be obtained, defined as relatively "high responders" (individual fasting glucose change > median value) or relatively "low responders" (individual fasting glucose change < median value) to metformin monotherapy.	Drug: Metformin Metformin, pills, 850 mg three times a day for three months

Arms

Assigned Interventions

Metformin

At study entry, all oral hypoglycemic agents will be discontinued for 5 days and then metformin (2,550 mg/daily) will be given for 3 months. Fasting plasma glucose will be measured at baseline and 3 months after metformin treatment. Patients will be stratified according to the median value of metformin efficacy as indicated by fasting glucose change after metformin treatment (i.e. baseline fasting glucose minus 3-month fasting glucose).

So, two subgroups of patients will be obtained, defined as relatively "high responders" (individual fasting glucose change > median value) or relatively "low responders" (individual fasting glucose change < median value) to metformin monotherapy.

Drug: Metformin

Metformin, pills, 850 mg three times a day for three months

Eligibility

Ages Eligible for Study:	40 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01334684

Contacts

Contact: Salvatore De Cosmo, MD	+39088241067	s.decosmo@operapadrepio.it
Contact: Ornella Ludovico, MD	+390882410625	o.ludovico@operapadrepio.it

Locations

Italy
Casa Sollievo Della Sofferenza IRCCS	Not yet recruiting
San Giovanni Rotondo, Foggia, Italy, 71013

Sponsors and Collaborators

Casa Sollievo della Sofferenza IRCCS

University Hospital, Catania

Investigators

Study Chair:

Salvatore De Cosmo, MD

Casa Sollievo della Sofferenza IRCCS

More Information

Publications:

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. Epub 2008 Oct 22.

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.

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.

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.

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.

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. Epub 2008 Jan 9.

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. Epub 2009 Jan 4.

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.

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. Summary for patients in: Ann Intern Med. 2010 Oct 5;153(7):I20.

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. Epub 2010 Jul 16.

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.

Responsible Party:	Salvatore De Cosmo, Casa Sollievo della Sofferenza IRCCS
ClinicalTrials.gov Identifier:	NCT01334684 History of Changes
Other Study ID Numbers:	GExpProMet
Study First Received:	April 12, 2011
Last Updated:	April 12, 2011
Health Authority:	Italy: Ethics Committee

Keywords provided by Casa Sollievo della Sofferenza IRCCS:

Type 2 Diabetes Mellitus
Metformin Efficacy
Gene Expression Profiles
Personalized Medicine

Additional relevant MeSH terms:

Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases

Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013