Clinical trial NCT01369680
Conditions: Chronic Pain
Keywords: Ketamine Chronic pain Children Oral pain medication
Sponsor: University of Rochester
Start date: 2011-05-01; Completion date: 2012-10-01
Enrollment: 12 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: The first three subjects were administered 0.25 mg/kg/dose oral ketamine. arm 2: The second group of three subjects were administered 0.5 mg/kg/dose oral ketamine. arm 3: The third group of three subjects were administered 1 mg/kg/dose oral ketamine. arm 4: The fourth group of three subjects were administered 1.5 mg/kg/dose oral ketamine.
Interventions: intervention 1: Ketamine
Intervention descriptions: intervention 1: 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.

Protocol documents: