Oral Ketamine for Control of Chronic Pain in Children
Condition: Chronic Pain
MeSH terms: Chronic Pain
Study type: Interventional
Phase: Phase 1

Summary: 
      The study is a maximum tolerated dose finding study for oral, chronic, daily administration
      of oral ketamine (by mouth) in children with long-term daily pain.
    

Detailed description: 
      Pain control in children is a major concern when children have chronic diseases, such as
      cancer and sickle cell disease with frequent pain crises. Additionally, though the
      traditional pain medications of morphine and acetaminophen are regarded as safe and effective
      for pain control in children, there are few alternative therapies available when these
      medications are insufficient. Chronic pain (whether cancer or non-cancer pain) in children
      has few approved and well tolerated therapeutic options with proven efficacy.

      Ketamine is a medication that was first described in 1962[1]. It is an NMDA-R
      (N-methyl-D-aspartate-receptor) antagonist with dissociative amnestic and analgesic
      effects[1-2]. Ketamine is particularly successful as a dissociative amnestic for children in
      the emergent setting as it has little respiratory or cardiac impact, has a short half-life,
      and has fewer psychomimetic effects in the pediatric population than in adults[1]. Its
      function is via antagonism and reduction of NMDA-receptors in the afferent pain pathway. In
      effect, this decreases pain receptors and can dramatically reduce the need for narcotic pain
      medications for patients with chronic pain.

      Unfortunately, with such dissociative effects, ketamine has been a drug of abuse for
      decades[1,3]. Additionally, there is concern that ketamine may have long-term deleterious
      effects on cognition for those subjects chronically exposed to IV ketamine[4], especially
      children whose neural pathways may still be developing[1,5]. These effects may include
      difficulty with attention and working memory, though the effects appear to be short-term and
      reversible in adults. However, much of this data is derived from rodent or primate studies,
      and there is little evidence that there are long-term cognitive effects on humans chronically
      exposed to ketamine[1]. This lack of data is particularly impactful in the pediatric group.

      Ketamine has been evaluated as an analgesic medication for patients with chronic pain that is
      not resolved with narcotics and gabapentin. There are a number of case reports and small case
      series that suggest ketamine is a useful medication for control of chronic pain in
      adults[2,4,6-8]. Additionally, there are case studies that describe lasting (12 week) pain
      control in adults after 4-10 days of ketamine therapy[7-8]. However, there are, to date,
      little data that aid a pediatrician in determining if ketamine is a safe and effective option
      as a chronic, oral therapy for children with chronic pain.

      Overall, there are few proven safe and effective medications for use in chronic pain
      management for children. Ketamine is a well known medication with a well elaborated safety
      profile, when given intravenously and for short periods of time. There is, as above, emerging
      data that ketamine is useful for chronic pain control in adults. The question that remains to
      be answered is whether ketamine is a safe option for chronic use in children, whose brains
      are significantly more plastic and whose metabolism is different compared with those of
      adults.
    

Intervention name(s): Ketamine
Intervention type(s): Drug
Intervention description(s): Drug will be given orally three times a day at doses escalating from 0.25mg/kg/dose to 1.5mg/kg/dose in cohorts of 3. Each subject will be administered study drug for 2 weeks.
Other intervention name(s): Ketalar; Ketamine hydrochloride
Intervention MeSH terms: Ketamine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ketamine; Chronic pain; Children; Oral pain medication