drugset / Trial / NCT03580967
Vortioxetine Monotherapy for Major Depressive Disorder in Type 2 Diabetes
NaSingle-groupOpen-labelTreatment
Summary
This study will enroll participants who have been diagnosed with type 2 diabetes and are experiencing symptoms of depression. This study will look at an anti-depressant medication called vortioxetine (Trintellix). Vortioxetine is an oral medication (pill) that has been approved by the US Food and Drug Administration (FDA) to treat depression in adults. The purpose of this study is to look at what effects (if any) vortioxetine may have on symptoms of depression in patients with type 2 diabetes. This study will also look at what effects (if any) vortioxetine has on blood sugar, and how vortioxetine may improve the way our brains are able to adapt and respond to stress.
Timeline
- Start
- 2019-07-01
- Primary completion
- 2021-07-01
- Completion
- 2021-07-01
Publications
- Background Centers for Disease Control and Prevention, National Diabetes Statistics Report. National diabetes statistics report. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf. (2017).
- Background Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care. 2001 Jun;24(6):1069-78. doi: 10.2337/diacare.24.6.1069.
- Background Gavard JA, Lustman PJ, Clouse RE. Prevalence of depression in adults with diabetes. An epidemiological evaluation. Diabetes Care. 1993 Aug;16(8):1167-78. doi: 10.2337/diacare.16.8.1167.
- Background de Groot M, Doyle T, Hockman E, Wheeler C, Pinkerman B, Shubrook J, Gotfried R, Schwartz F. Depression among type 2 diabetes rural Appalachian clinic attendees. Diabetes Care. 2007 Jun;30(6):1602-4. doi: 10.2337/dc06-1599. Epub 2007 Mar 12. No abstract available.
- Background Lustman PJ, Anderson RJ, Freedland KE, de Groot M, Carney RM, Clouse RE. Depression and poor glycemic control: a meta-analytic review of the literature. Diabetes Care. 2000 Jul;23(7):934-42. doi: 10.2337/diacare.23.7.934.
- Background de Groot M, Anderson R, Freedland KE, Clouse RE, Lustman PJ. Association of depression and diabetes complications: a meta-analysis. Psychosom Med. 2001 Jul-Aug;63(4):619-30. doi: 10.1097/00006842-200107000-00015.
- Background Ciechanowski PS, Katon WJ, Russo JE. Depression and diabetes: impact of depressive symptoms on adherence, function, and costs. Arch Intern Med. 2000 Nov 27;160(21):3278-85. doi: 10.1001/archinte.160.21.3278.
- Background Jacobson AM, de Groot M, Samson JA. The effects of psychiatric disorders and symptoms on quality of life in patients with type I and type II diabetes mellitus. Qual Life Res. 1997 Jan;6(1):11-20. doi: 10.1023/a:1026487509852.
- Background Egede LE, Osborn CY. Role of motivation in the relationship between depression, self-care, and glycemic control in adults with type 2 diabetes. Diabetes Educ. 2010 Mar-Apr;36(2):276-83. doi: 10.1177/0145721710361389. Epub 2010 Feb 23.
- Background Katon W, von Korff M, Ciechanowski P, Russo J, Lin E, Simon G, Ludman E, Walker E, Bush T, Young B. Behavioral and clinical factors associated with depression among individuals with diabetes. Diabetes Care. 2004 Apr;27(4):914-20. doi: 10.2337/diacare.27.4.914.
- Background Katon WJ, Rutter C, Simon G, Lin EH, Ludman E, Ciechanowski P, Kinder L, Young B, Von Korff M. The association of comorbid depression with mortality in patients with type 2 diabetes. Diabetes Care. 2005 Nov;28(11):2668-72. doi: 10.2337/diacare.28.11.2668.
- Background Egede LE, Zheng D, Simpson K. Comorbid depression is associated with increased health care use and expenditures in individuals with diabetes. Diabetes Care. 2002 Mar;25(3):464-70. doi: 10.2337/diacare.25.3.464.
- Background Baumeister H, Hutter N, Bengel J. Psychological and pharmacological interventions for depression in patients with diabetes mellitus and depression. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD008381. doi: 10.1002/14651858.CD008381.pub2.
- Background van der Feltz-Cornelis CM, Nuyen J, Stoop C, Chan J, Jacobson AM, Katon W, Snoek F, Sartorius N. Effect of interventions for major depressive disorder and significant depressive symptoms in patients with diabetes mellitus: a systematic review and meta-analysis. Gen Hosp Psychiatry. 2010 Jul-Aug;32(4):380-95. doi: 10.1016/j.genhosppsych.2010.03.011. Epub 2010 May 15.
- Background Champaneri S, Wand GS, Malhotra SS, Casagrande SS, Golden SH. Biological basis of depression in adults with diabetes. Curr Diab Rep. 2010 Dec;10(6):396-405. doi: 10.1007/s11892-010-0148-9.
- Background Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.
- Background Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009 May 1;65(9):732-41. doi: 10.1016/j.biopsych.2008.11.029. Epub 2009 Jan 15.
- Background Stuart MJ, Baune BT. Depression and type 2 diabetes: inflammatory mechanisms of a psychoneuroendocrine co-morbidity. Neurosci Biobehav Rev. 2012 Jan;36(1):658-76. doi: 10.1016/j.neubiorev.2011.10.001. Epub 2011 Oct 14.
- Background Pickup JC. Inflammation and activated innate immunity in the pathogenesis of type 2 diabetes. Diabetes Care. 2004 Mar;27(3):813-23. doi: 10.2337/diacare.27.3.813.
- Background de Jonge P, Rosmalen JG. Comment on: Knol MJ, Twisk JWR, Beekman ATF, Heine RJ, Snoek FJ, Pouwer F. (2006) depression as a risk factor for the onset of type 2 diabetes mellitus. A meta-analysis. Diabetologia; 49: 837-845. Diabetologia. 2006 Nov;49(11):2797-8; author reply 2799-800. doi: 10.1007/s00125-006-0389-y. Epub 2006 Aug 18. No abstract available.
- Background Ruhe HG, Mason NS, Schene AH. Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Mol Psychiatry. 2007 Apr;12(4):331-59. doi: 10.1038/sj.mp.4001949. Epub 2007 Jan 16.
- Background Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol. 2006 Jan;27(1):24-31. doi: 10.1016/j.it.2005.11.006. Epub 2005 Nov 28.
- Background Doyle TA, de Groot M, Harris T, Schwartz F, Strotmeyer ES, Johnson KC, Kanaya A. Diabetes, depressive symptoms, and inflammation in older adults: results from the Health, Aging, and Body Composition Study. J Psychosom Res. 2013 Nov;75(5):419-24. doi: 10.1016/j.jpsychores.2013.08.006. Epub 2013 Aug 16.
- Background Alvarez A, Faccioli J, Guinzbourg M, Castex MM, Bayon C, Masson W, Bluro I, Kozak A, Sorroche P, Capurro L, Grosembacher L, Proietti A, Finkelsztein C, Costa L, Fainstein Day P, Cagide A, Litwak LE, Golden SH. Endocrine and inflammatory profiles in type 2 diabetic patients with and without major depressive disorder. BMC Res Notes. 2013 Feb 14;6:61. doi: 10.1186/1756-0500-6-61.
- Background Hood KK, Lawrence JM, Anderson A, Bell R, Dabelea D, Daniels S, Rodriguez B, Dolan LM; SEARCH for Diabetes in Youth Study Group. Metabolic and inflammatory links to depression in youth with diabetes. Diabetes Care. 2012 Dec;35(12):2443-6. doi: 10.2337/dc11-2329. Epub 2012 Oct 1.
- Background Yoshimura R, Hori H, Ikenouchi-Sugita A, Umene-Nakano W, Ueda N, Nakamura J. Higher plasma interleukin-6 (IL-6) level is associated with SSRI- or SNRI-refractory depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Jun 15;33(4):722-6. doi: 10.1016/j.pnpbp.2009.03.020. Epub 2009 Mar 28.
- Background Myint AM, Kim YK. Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses. 2003 Nov-Dec;61(5-6):519-25. doi: 10.1016/s0306-9877(03)00207-x.
- Background Munipally PK, Agraharm SG, Valavala VK, Gundae S, Turlapati NR. Evaluation of indoleamine 2,3-dioxygenase expression and kynurenine pathway metabolites levels in serum samples of diabetic retinopathy patients. Arch Physiol Biochem. 2011 Dec;117(5):254-8. doi: 10.3109/13813455.2011.623705. Epub 2011 Oct 29.
- Background Doyle T, Halaris A, Rao M. Shared neurobiological pathways between type 2 diabetes and depressive symptoms: a review of morphological and neurocognitive findings. Curr Diab Rep. 2014 Dec;14(12):560. doi: 10.1007/s11892-014-0560-7.
- Background Fossati P, Radtchenko A, Boyer P. Neuroplasticity: from MRI to depressive symptoms. Eur Neuropsychopharmacol. 2004 Dec;14 Suppl 5:S503-10. doi: 10.1016/j.euroneuro.2004.09.001.
- Background Reagan LP. Diabetes as a chronic metabolic stressor: causes, consequences and clinical complications. Exp Neurol. 2012 Jan;233(1):68-78. doi: 10.1016/j.expneurol.2011.02.004. Epub 2011 Feb 12.
- Background Ho N, Sommers MS, Lucki I. Effects of diabetes on hippocampal neurogenesis: links to cognition and depression. Neurosci Biobehav Rev. 2013 Sep;37(8):1346-62. doi: 10.1016/j.neubiorev.2013.03.010. Epub 2013 May 13.
- Background Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis. 2009 Mar;24(1):27-53. doi: 10.1007/s11011-008-9118-1. Epub 2008 Dec 16.
- Background Koehl M, Abrous DN. A new chapter in the field of memory: adult hippocampal neurogenesis. Eur J Neurosci. 2011 Mar;33(6):1101-14. doi: 10.1111/j.1460-9568.2011.07609.x.
- Background Snyder JS, Hong NS, McDonald RJ, Wojtowicz JM. A role for adult neurogenesis in spatial long-term memory. Neuroscience. 2005;130(4):843-52. doi: 10.1016/j.neuroscience.2004.10.009.
- Background Ajilore O, Narr K, Rosenthal J, Pham D, Hamilton L, Watari K, Elderkin-Thompson V, Darwin C, Toga A, Kumar A. Regional cortical gray matter thickness differences associated with type 2 diabetes and major depression. Psychiatry Res. 2010 Nov 30;184(2):63-70. doi: 10.1016/j.pscychresns.2010.07.003. Epub 2010 Sep 15.
- Background Kumar A, Gupta R, Thomas A, Ajilore O, Hellemann G. Focal subcortical biophysical abnormalities in patients diagnosed with type 2 diabetes and depression. Arch Gen Psychiatry. 2009 Mar;66(3):324-30. doi: 10.1001/archgenpsychiatry.2008.548.
- Background Kumar A, Haroon E, Darwin C, Pham D, Ajilore O, Rodriguez G, Mintz J. Gray matter prefrontal changes in type 2 diabetes detected using MRI. J Magn Reson Imaging. 2008 Jan;27(1):14-9. doi: 10.1002/jmri.21224.
- Background Awad N, Gagnon M, Messier C. The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol. 2004 Nov;26(8):1044-80. doi: 10.1080/13803390490514875.
- Background Connolly KR, Thase ME. Vortioxetine: a New Treatment for Major Depressive Disorder. Expert Opin Pharmacother. 2016;17(3):421-31. doi: 10.1517/14656566.2016.1133588.
- Background Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.
- Background Mork A, Pehrson A, Brennum LT, Nielsen SM, Zhong H, Lassen AB, Miller S, Westrich L, Boyle NJ, Sanchez C, Fischer CW, Liebenberg N, Wegener G, Bundgaard C, Hogg S, Bang-Andersen B, Stensbol TB. Pharmacological effects of Lu AA21004: a novel multimodal compound for the treatment of major depressive disorder. J Pharmacol Exp Ther. 2012 Mar;340(3):666-75. doi: 10.1124/jpet.111.189068. Epub 2011 Dec 9.
- Background Westrih I, Rehrson A, & Zhong H, et al. In vitro and in vivo effects for the multimodal antidepressant vortioxetine (Lu AA21004) at human and rat targets. International Journal of Psychiatry and Clinical Practice 2012; 16 (S1): 47.
- Background Florea I, Loft H, Danchenko N, Rive B, Brignone M, Merikle E, Jacobsen PL, Sheehan DV. The effect of vortioxetine on overall patient functioning in patients with major depressive disorder. Brain Behav. 2017 Feb 2;7(3):e00622. doi: 10.1002/brb3.622. eCollection 2017 Mar.
- Background McIntyre RS, Harrison J, Loft H, Jacobson W, Olsen CK. The Effects of Vortioxetine on Cognitive Function in Patients with Major Depressive Disorder: A Meta-Analysis of Three Randomized Controlled Trials. Int J Neuropsychopharmacol. 2016 Jun 15;19(10):pyw055. doi: 10.1093/ijnp/pyw055.
- Background Nomikos GG, Tomori D, Zhong W, Affinito J, Palo W. Efficacy, safety, and tolerability of vortioxetine for the treatment of major depressive disorder in patients aged 55 years or older. CNS Spectr. 2017 Aug;22(4):348-362. doi: 10.1017/S1092852916000626. Epub 2016 Nov 21.
- Background de Groot M, Doyle T, Kushnick M, Shubrook J, Merrill J, Rabideau E, Schwartz F. Can lifestyle interventions do more than reduce diabetes risk? Treating depression in adults with type 2 diabetes with exercise and cognitive behavioral therapy. Curr Diab Rep. 2012 Apr;12(2):157-66. doi: 10.1007/s11892-012-0261-z.
- Background Calabrese JR, Skwerer RG, Barna B, Gulledge AD, Valenzuela R, Butkus A, Subichin S, Krupp NE. Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res. 1986 Jan;17(1):41-7. doi: 10.1016/0165-1781(86)90040-5.
- Background Funakoshi-Tago M, Shimizu T, Tago K, Nakamura M, Itoh H, Sonoda Y, Kasahara T. Celecoxib potently inhibits TNFalpha-induced nuclear translocation and activation of NF-kappaB. Biochem Pharmacol. 2008 Sep 1;76(5):662-71. doi: 10.1016/j.bcp.2008.06.015. Epub 2008 Jul 3.
- Background Hayashino Y, Mashitani T, Tsujii S, Ishii H; Diabetes Distress and Care Registry at Tenri Study Group. Elevated levels of hs-CRP are associated with high prevalence of depression in japanese patients with type 2 diabetes: the Diabetes Distress and Care Registry at Tenri (DDCRT 6). Diabetes Care. 2014 Sep;37(9):2459-65. doi: 10.2337/dc13-2312. Epub 2014 Jun 26.
- Background Husain MM, Rush AJ, Trivedi MH, McClintock SM, Wisniewski SR, Davis L, Luther JF, Zisook S, Fava M. Pain in depression: STAR*D study findings. J Psychosom Res. 2007 Aug;63(2):113-22. doi: 10.1016/j.jpsychores.2007.02.009.
- Background Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology. 2000 Apr;22(4):370-9. doi: 10.1016/S0893-133X(99)00134-7.
- Background Leuchter AF, Husain MM, Cook IA, Trivedi MH, Wisniewski SR, Gilmer WS, Luther JF, Fava M, Rush AJ. Painful physical symptoms and treatment outcome in major depressive disorder: a STAR*D (Sequenced Treatment Alternatives to Relieve Depression) report. Psychol Med. 2010 Feb;40(2):239-51. doi: 10.1017/S0033291709006035. Epub 2009 Jun 3.
- Background Lieb J, Karmali R, Horrobin D. Elevated levels of prostaglandin E2 and thromboxane B2 in depression. Prostaglandins Leukot Med. 1983 Apr;10(4):361-7. doi: 10.1016/0262-1746(83)90048-3.
- Background Miller CL, Llenos IC, Dulay JR, Weis S. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res. 2006 Feb 16;1073-1074:25-37. doi: 10.1016/j.brainres.2005.12.056. Epub 2006 Jan 30.
- Background Miller GE, Rohleder N, Cole SW. Chronic interpersonal stress predicts activation of pro- and anti-inflammatory signaling pathways 6 months later. Psychosom Med. 2009 Jan;71(1):57-62. doi: 10.1097/PSY.0b013e318190d7de. Epub 2008 Dec 10.
- Background Myint AM, Kim YK, Verkerk R, Park SH, Scharpe S, Steinbusch HW, Leonard BE. Tryptophan breakdown pathway in bipolar mania. J Affect Disord. 2007 Sep;102(1-3):65-72. doi: 10.1016/j.jad.2006.12.008. Epub 2007 Jan 30.
- Background Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord. 2007 Feb;98(1-2):143-51. doi: 10.1016/j.jad.2006.07.013. Epub 2006 Sep 6.
- Background O'Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG. Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res. 2007 Apr-Jun;41(3-4):326-31. doi: 10.1016/j.jpsychires.2006.05.013. Epub 2006 Jul 25.
- Background Pilowsky I, Spence N, Cobb J, Katsikitis M. The Illness Behavior Questionnaire as an aid to clinical assessment. Gen Hosp Psychiatry. 1984 Apr;6(2):123-30. doi: 10.1016/0163-8343(84)90070-7.
- Background Riondino S, Trifiro E, Principessa L, Mascioletti S, Di Renzo L, Gaudio C, Biasucci LM, Crea F, Pulcinelli FM. Lack of biological relevance of platelet cyclooxygenase-2 dependent thromboxane A2 production. Thromb Res. 2008;122(3):359-65. doi: 10.1016/j.thromres.2007.12.011. Epub 2008 Mar 4.
- Background Rosenbaum D, Haipt A, Fuhr K, Haeussinger FB, Metzger FG, Nuerk HC, Fallgatter AJ, Batra A, Ehlis AC. Aberrant functional connectivity in depression as an index of state and trait rumination. Sci Rep. 2017 May 19;7(1):2174. doi: 10.1038/s41598-017-02277-z.
- Background Drysdale AT, Grosenick L, Downar J, Dunlop K, Mansouri F, Meng Y, Fetcho RN, Zebley B, Oathes DJ, Etkin A, Schatzberg AF, Sudheimer K, Keller J, Mayberg HS, Gunning FM, Alexopoulos GS, Fox MD, Pascual-Leone A, Voss HU, Casey BJ, Dubin MJ, Liston C. Resting-state connectivity biomarkers define neurophysiological subtypes of depression. Nat Med. 2017 Jan;23(1):28-38. doi: 10.1038/nm.4246. Epub 2016 Dec 5.
- Background Cohen, J. (1988). Statistical Power Analyses for the Behavioral Sciences (2nd Edition). Psychology Press. Taylor & Francis Group.
- Background de Groot M, Doyle T, Averyt J, Risaliti C, Shubroo J. Depressive symptoms and type 2 diabetes mellitus in rural appalachia: an 18-month follow-up study. Int J Psychiatry Med. 2015;48(4):263-77. doi: 10.2190/PM.48.4.c.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Vortioxetine | Unknown | 10 mg | Oral |
| Subject | Vortioxetine | Unknown | 20 mg | Oral |