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

NCT00431171 | Completed Phase 1

• 1 other identifier: CN101
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Spinal Cord Injuries

Keywords

spinal cord injuries; lithium

Outcome Measures

Primary Outcomes (1)

• Incidence of clinical adverse events including known and unknown adverse events, and changes from baseline in vital signs, ECGs and laboratory parameters

Secondary Outcomes (1)

• Plasma lithium level

Interventions

Lithium carbonate DRUG

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects of either gender and 18 - 60 years of age (preferably 10 males and females each)
• Subjects with chronic spinal cord injury (defined as 12 months or more post spinal cord injury), as confirmed by a MRI
• Subjects with neurological status: ASIA A, B or C
• Subjects must be able to read, understand, and complete the VAS
• Subjects who have voluntarily signed\* and dated\* an informed consent form, approved by an IEC/IRB, prior to any study-specific procedures \*If a subject consents to participation but is not in a position to personally sign and date the informed consent form because of his or her physical condition, the consent must be confirmed at the time of consent orally, signed on behalf by the subject's relative, and by an impartial witness who is present throughout the whole informed consent process.

You may not qualify if:

• a history of hypersensitivity to lithium
• significant renal, cardiovascular, hepatic and psychiatric diseases
• significant medical diseases or infection
• brain injury
• Addison's disease
• debilitation or dehydration
• recently taken or are taking diuretics or other drugs with known interaction with lithium, such as tricyclic antidepressants, NSAIDs and tetracycline
• a history of alcohol abuse or drug abuse, or if they are
• pregnant or lactating women;
• female of childbearing potential and are unwilling to use an effective contraceptive method while enrolled in the study;
• subjects who are currently participating in another investigational study or have been taking any investigational drug within the last 4 weeks prior to screening of this study (Visit 1); and finally,
• any criteria, which, in the opinion of the investigator, suggest that the subject would not be compliant with the study protocol.

Sponsors & Collaborators

• The University of Hong Kong: lead
• China Spinal Cord Injury Network: collaborator

Study Sites (1)

MacLehose Medical Rehabilitation Centre

Pokfulam, Hong Kong SAR, China

Location

Related Publications (23)

• Yick LW, So KF, Cheung PT, Wu WT. Lithium chloride reinforces the regeneration-promoting effect of chondroitinase ABC on rubrospinal neurons after spinal cord injury. J Neurotrauma. 2004 Jul;21(7):932-43. doi: 10.1089/neu.2004.21.932.

  PMID: 15307905 BACKGROUND

• Phiel CJ, Klein PS. Molecular targets of lithium action. Annu Rev Pharmacol Toxicol. 2001;41:789-813. doi: 10.1146/annurev.pharmtox.41.1.789.

  PMID: 11264477 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.

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• 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.

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• 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.

  PMID: 10877522 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.

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• 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.

  PMID: 15165456 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.

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• 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.

  PMID: 10880530 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.

  PMID: 15056276 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.

  PMID: 12447396 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.

  PMID: 12140783 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.

  PMID: 14699963 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.

  PMID: 14534419 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.

  PMID: 12605892 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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• 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.

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• 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.

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• Gitlin M. Lithium and the kidney: an updated review. Drug Saf. 1999 Mar;20(3):231-43. doi: 10.2165/00002018-199920030-00004.

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• Grignon S, Bruguerolle B. Cerebellar lithium toxicity: a review of recent literature and tentative pathophysiology. Therapie. 1996 Mar-Apr;51(2):101-6.

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• 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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Related Links

• The results of the the captioned study was published in Spinal Cord (2011) ,49 issue

MeSH Terms

Conditions

Spinal Cord Injuries

Interventions

Lithium Carbonate

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Carbonates; Alkalies; Inorganic Chemicals; Carbonic Acid; Carbon Compounds, Inorganic; Lithium Compounds

Study Officials

• Yat-wa Wong, MD

  The University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 1, 2007
• First Posted: February 5, 2007
• Study Start: September 1, 2007
• Primary Completion: January 1, 2010
• Study Completion: January 1, 2010
• Last Updated: January 16, 2012

Record last verified: 2012-01

Locations

CN (1)