Safety and Pharmacokinetics Study of Oral Lithium in Patients With Chronic Spinal Cord Injury
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Three Month, Open-label, Single-arm Trial Evaluating the Safety and Pharmacokinetics of Oral Lithium in Patients Diagnosed With Chronic Spinal Cord Injury|
- Incidence of clinical adverse events including known and unknown adverse events, and changes from baseline in vital signs, ECGs and laboratory parameters
- Plasma lithium level
|Study Start Date:||September 2007|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Patients with spinal cord injury (SCI) usually have permanent and often devastating neurological deficits and disability. There has been successful research in a number of fields that may someday help people with spinal cord injuries.
The planned treatment trials will focus on the effects of oral lithium on neurological function in people with chronic spinal cord injury and those that have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.
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.
Lithium attracted much attention as a potential neuroregenerative therapy based on experiments in animal models of SCI in 2004. However, toxic levels of lithium (>1.5 mmol/L) are close to the effective levels (0.6 - 1.2 mmol/L). At toxic levels, patients may become confused and lethargic, have diarrhea, upset stomach, and develop tremors, ataxia, dysarthria, and nystagmus. Lithium toxicity may be compounded by sodium depletion or diuretics (thiazides) that inhibit kidney sodium upgrade and ACE inhibitors. Plasma levels also depend on fluid input/output. Therefore, care will be taken to titrate the dose and to test plasma levels of the drug at the beginning, at day 2, 7, and week 6 during the treatment period.
Acute toxicity usually produces relatively mild symptoms. Chronic lithium toxicity may lead to more severe neurotoxic symptoms. However, these symptoms usually develop after 3-5 years of treatment.
Data obtained from this study will be used to develop future chronic spinal cord injury clinical studies: (1) randomized controlled trials with lithium versus placebo; and (2) randomized controlled trials comparing effects of lithium and placebo on subjects who have received umbilical cord blood mononuclear cell transplants to the spinal cord.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00431171
|China, Hong Kong SAR|
|MacLehose Medical Rehabilitation Centre|
|Pokfulam, Hong Kong SAR, China|
|Principal Investigator:||Yat-wa Wong, MD||The University of Hong Kong|