The purpose of the study is to document the improvements observed during the pilot study. In order to reach the next level of confidence in the treatment, there must be a rigorous, systematic study of its effects and its safety.
In 2011, JBRF sponsored investigators applied to the Federal Drug Administration (FDA) to use ketamine, previously approved for use as a sedation agent, on children for the purpose of diminishing the symptoms of mood disorder. After FDA approval, which is a very thorough review of the drug’s prior use and the rationale for using the drug for the proposed purpose, investigators applied for, and received Internal Review Board (IRB) approval the study. The purpose of an IRB is to provide patient safety oversight during the entire course of the study.
While there is leeway in the methods that can be used for a formal study, the more controls that are put on the experiment that would limit the possibility for variation and subjective opinions, the better. In this study, the following controls are being used:
- The effect of the drug will be compared to the effects of no-drug (placebo)
- The effect of the drug will be compared between children who are described by FOH and those who have a diagnosis of bipolar disorder but are not described by FOH.
- Neither the person giving the administration nor the person receiving the administration will know if it is drug or placebo.
In the pilot study, the upward titration of the drug was a result of Dr. Papolos’ subjective experience. Here, that experience has been used to define the minimum and maximum amount of drug that can be administered (maximum dose is well within the range used in the pilot study), but the actual amount of drug that will be used during any administration will be the result of a programmed algorithm which considers:
- Degree of side effects
- Achievement or loss of a therapeutic response as determined by two questionnaires which measure manic behavior and aggression.
While Dr. Papolos will not determine the quantity of drug to be given, a description of the side effects experienced by the child at the last administration will be given to him and, based on those, he will provide instructions as to the pacing and increments to be used for the next administration. This is to ensure the safety of the children.
The study takes place over a period of 18 days. A breakdown of what happens on each of those days can be seen here. Generally:
- Parents will provide the answers to all behavioral questionnaires. It is necessary that the same adult respond to all questionnaires throughout the study. The questionnaires will be administered by a Research Assistant and will be given before, during and after the administrations of drug/placebo. The Research Assistants will also give the child 3 neurocognitive tests; once on the first day of the study and again on the last day.
- During 4 of the mornings in the middle of the study, a medical staff member will administer the drug or placebo to the child. This person will be a Nurse, Advanced Practice Nurse, Physician’s Assistant or Nurse Practitioner. In addition to administering the drug/placebo, he or she will assess and monitor the child’s health and degree of side effects.
- Dr. Papolos will be on-call 24/7 to respond to concerns.