A three-month, open-label, single-arm trial evaluating the safety and pharmacokinetics of oral lithium in patients with chronic spinal cord injury

Abstract

Objectives: Lithium has recently been found to enhance neuronal regeneration and differentiation. This arouses its potential use to treat spinal cord injury patients. The safety and pharmacokinetics of lithium are not verified for this group of patients as their internal organ functions may change. This is a phase 1 clinical trial to evaluate the safety and pharmacokinetics of lithium in spinal cord injury patients. Methods: A total of 20 chronic spinal cord injury subjects were recruited. Oral lithium carbonate was given in divided dose to maintain the serum lithium level 0.6-1.2 mmol l À1 for 6 weeks. Safety parameters, adverse events and pharmacokinetic data were carefully collected and monitored. Results: No severe adverse event was documented. All blood parameters remained stable. Nausea and vomiting were the most common complaints but tolerance was improved in 2 weeks for most subjects. A wide range of oral doses was required to maintain serum lithium level at the targeted range. However, the dose for individual subject was relatively constant. Conclusion: This phase 1 clinical trial is the first report indicating the safety of lithium in chronic spinal cord injury patients. It is well tolerated after the first 2 weeks. Individual titration of lithium is essential to maintain an optimal serum lithium level but once the desirable level is achieved, the oral dose remains relatively unchanged for maintenance.Spinal Cord (2011) 49, 94-98;

Efficacy and safety of lithium carbonate treatment of chronic spinal cord injuries: a double-blind, randomized, placebo-controlled clinical trial

“…14 Thus, lithium has many effects that are potentially neuroregenerative for spinal cord injury. In 2011, Wong et al 2 reported that lithium can be safely given to chronic spinal cord injury patients and can be maintained in a therapeutic range of 0.6-1.2 mmol l À1 over a 6-week period. We consequently designed the current phase II clinical trial to assess the effectiveness of 6-week oral lithium carbonate treatment of chronic spinal cord injury.…”

“…In 2011, Wong et al 2 reported the safety and pharmacokinetic study of lithium in chronic spinal cord injury patients. Wong's investigation is the first step of series of clinical trials supported by the China Spinal Cord Injury Network to assess the effects of umbilical cord blood and lithium on chronic spinal cord injury.…”

Translational Regenerative Therapies for Chronic Spinal Cord Injury

“…It should be noted that further trials in SCI patients are being conducted all over the world, but they are not performed under strict regulatory environments so caution is advised when assessing the results of such studies until further work is done in order to confirm findings in a better regulated setting [ 39 , 40 , 41 , 42 , 43 , 44 , 45 ].…”

Pharmacology of riluzole in acute spinal cord injury

“…However, beyond supportive care, there are no medical or surgical treatments that have been clearly demonstrated to improve functional outcome after SCI in humans. Clinical trials with methylprednisolone (NASCIS [National Acute Spinal Cord Injury Study] II and III), 8,9 GM-1 ganglioside, 17 fampridine (4-aminopyridine), 22,23,38 and lithium carbonate 58,59 have provided suggestive but equivocal evidence of benefit.…”