Safety and Pharmacokinetics Study of Oral Lithium in Patients With Chronic Spinal Cord Injury
Condition: Spinal Cord Injuries
MeSH terms: Spinal Cord Injuries; Wounds and Injuries
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      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.
    

Intervention name(s): Lithium carbonate
Intervention type(s): Drug
Intervention MeSH terms: Lithium Carbonate
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: spinal cord injuries; lithium