Gene Expression Profiles and Metformin Efficacy in Type 2 Diabetes

NCT01334684 | Unknown DMC

• 1 other identifier: GExpProMet
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes

Keywords

Type 2 Diabetes Mellitus; Metformin Efficacy; Gene Expression Profiles; Personalized Medicine

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (1)

• 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

Study Arms (1)

Metformin

OTHER

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

Interventions

Metformin DRUG

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

Metformin

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Type 2 diabetes (duration of diabetes of at least 2 years)
• age 40-70 yrs
• HbA1c \> 6.4 \< 9.0

You may not qualify if:

• insulin therapy
• contraindications to metformin use

Sponsors & Collaborators

• Casa Sollievo della Sofferenza IRCCS: lead
• University Hospital, Catania: collaborator

Study Sites (1)

Casa Sollievo Della Sofferenza IRCCS

San Giovanni Rotondo, Foggia, 71013, Italy

Location

Related Publications (11)

• 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.

  PMID: 18945920 BACKGROUND

• 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. doi: 10.1200/JCO.2005.09.078.

  PMID: 15659489 BACKGROUND

• 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. doi: 10.1158/0008-5472.CAN-04-2696.

  PMID: 15574762 BACKGROUND

• 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. doi: 10.1200/JCO.2004.05.166. Epub 2004 May 10.

  PMID: 15136595 BACKGROUND

• 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):372-379. doi: 10.1002/ijc.23501.

  PMID: 18449891 BACKGROUND

• 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.

  PMID: 18187804 BACKGROUND

• 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.

  PMID: 19122656 BACKGROUND

• 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.

  PMID: 20031539 BACKGROUND

• 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.

  PMID: 20921541 BACKGROUND

• 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 PPARgamma and Th2 cytokines. Atherosclerosis. 2010 Oct;212(2):668-73. doi: 10.1016/j.atherosclerosis.2010.07.002. Epub 2010 Jul 16.

  PMID: 20723894 BACKGROUND

• 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.

  PMID: 20406432 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Salvatore De Cosmo, MD

  Casa Sollievo della Sofferenza IRCCS

  STUDY CHAIR

Central Study Contacts

Salvatore De Cosmo, MD

CONTACT

+39088241067; s.decosmo@operapadrepio.it

Ornella Ludovico, MD

CONTACT

+390882410625; o.ludovico@operapadrepio.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 12, 2011
• First Posted: April 13, 2011
• Study Start: May 1, 2011
• Primary Completion: April 1, 2013
• Study Completion: September 1, 2013
• Last Updated: April 13, 2011

Record last verified: 2011-02

Locations

IT (1)