Safety and Pharmacokinetics Study of Oral Lithium in Patients With Chronic Spinal Cord Injury

Summary

The current study is a phase I open-label clinical trial to examine plasma levels after oral lithium treatments in 20 subjects with chronic spinal cord injury. The subjects will receive standard doses of oral lithium used in treatment of manic depression. The goal of the trial is to show feasibility and safety of maintaining plasma levels of 0.6 mmol/L to 1.2 mmol/L for six weeks in subjects with chronic spinal cord injury.

Timeline

Start

2007-09

Primary completion

2010-01

Completion

2010-01

Publications

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• Background Etheridge SL, Spencer GJ, Heath DJ, Genever PG. Expression profiling and functional analysis of wnt signaling mechanisms in mesenchymal stem cells. Stem Cells. 2004;22(5):849-60. doi: 10.1634/stemcells.22-5-849.
• Background Merendino RA, Arena A, Gangemi S, Ruello A, Losi E, Bene A, D'Ambrosio FP. In vitro interleukin-8 production by monocytes treated with lithium chloride from breast cancer patients. Tumori. 2000 Mar-Apr;86(2):149-52. doi: 10.1177/030089160008600208.
• Background Merendino RA, Arena A, Gangemi S, Ruello A, Losi E, Bene A, Valenti A, D'Ambrosio FP. In vitro effect of lithium chloride on interleukin-15 production by monocytes from IL-breast cancer patients. J Chemother. 2000 Jun;12(3):252-7. doi: 10.1179/joc.2000.12.3.252.
• Background Merendino RA, Mancuso G, Tomasello F, Gazzara D, Cusumano V, Chillemi S, Spadaro P, Mesiti M. Effects of lithium carbonate on cytokine production in patients affected by breast cancer. J Biol Regul Homeost Agents. 1994 Jul-Sep;8(3):88-91.
• Background De Boer J, Wang HJ, Van Blitterswijk C. Effects of Wnt signaling on proliferation and differentiation of human mesenchymal stem cells. Tissue Eng. 2004 Mar-Apr;10(3-4):393-401. doi: 10.1089/107632704323061753.
• Background de Boer J, Siddappa R, Gaspar C, van Apeldoorn A, Fodde R, van Blitterswijk C. Wnt signaling inhibits osteogenic differentiation of human mesenchymal stem cells. Bone. 2004 May;34(5):818-26. doi: 10.1016/j.bone.2004.01.016.
• Background Ohteki T, Parsons M, Zakarian A, Jones RG, Nguyen LT, Woodgett JR, Ohashi PS. Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3. J Exp Med. 2000 Jul 3;192(1):99-104. doi: 10.1084/jem.192.1.99.
• Background Kim JS, Chang MY, Yu IT, Kim JH, Lee SH, Lee YS, Son H. Lithium selectively increases neuronal differentiation of hippocampal neural progenitor cells both in vitro and in vivo. J Neurochem. 2004 Apr;89(2):324-36. doi: 10.1046/j.1471-4159.2004.02329.x.
• Background Aubert J, Dunstan H, Chambers I, Smith A. Functional gene screening in embryonic stem cells implicates Wnt antagonism in neural differentiation. Nat Biotechnol. 2002 Dec;20(12):1240-5. doi: 10.1038/nbt763. Epub 2002 Nov 25.
• Background Hellweg R, Lang UE, Nagel M, Baumgartner A. Subchronic treatment with lithium increases nerve growth factor content in distinct brain regions of adult rats. Mol Psychiatry. 2002;7(6):604-8. doi: 10.1038/sj.mp.4001042.
• Background Angelucci F, Mathe AA, Aloe L. Neurotrophic factors and CNS disorders: findings in rodent models of depression and schizophrenia. Prog Brain Res. 2004;146:151-65. doi: 10.1016/s0079-6123(03)46011-1.
• Background Shimomura A, Nomura R, Senda T. Lithium inhibits apoptosis of mouse neural progenitor cells. Neuroreport. 2003 Oct 6;14(14):1779-82. doi: 10.1097/00001756-200310060-00004.
• Background Hashimoto R, Senatorov V, Kanai H, Leeds P, Chuang DM. Lithium stimulates progenitor proliferation in cultured brain neurons. Neuroscience. 2003;117(1):55-61. doi: 10.1016/s0306-4522(02)00577-8.
• Background Willing AE, Zigova T, Milliken M, Poulos S, Saporta S, McGrogan M, Snable G, Sanberg PR. Lithium exposure enhances survival of NT2N cells (hNT neurons) in the hemiparkinsonian rat. Eur J Neurosci. 2002 Dec;16(12):2271-8. doi: 10.1046/j.1460-9568.2002.02300.x.
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• Background Chen KP, Shen WW, Lu ML. Implication of serum concentration monitoring in patients with lithium intoxication. Psychiatry Clin Neurosci. 2004 Feb;58(1):25-9. doi: 10.1111/j.1440-1819.2004.01188.x.
• Background Oakley PW, Whyte IM, Carter GL. Lithium toxicity: an iatrogenic problem in susceptible individuals. Aust N Z J Psychiatry. 2001 Dec;35(6):833-40. doi: 10.1046/j.1440-1614.2001.00963.x.
• Background Gitlin M. Lithium and the kidney: an updated review. Drug Saf. 1999 Mar;20(3):231-43. doi: 10.2165/00002018-199920030-00004.
• Background Grignon S, Bruguerolle B. Cerebellar lithium toxicity: a review of recent literature and tentative pathophysiology. Therapie. 1996 Mar-Apr;51(2):101-6.
• Background Kilts CD. The ups and downs of oral lithium dosing. J Clin Psychiatry. 1998;59 Suppl 6:21-6; discussion 27.
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