Use of D-cycloserine to Facilitate Extinction of Food Aversion in Pediatric Populations

• Extinction of fear is thought to use similar learning mechanisms as learning or conditioning of fear, and both are blocked by antagonists at the glutamatergic N-methyl-D-aspartate (NMDA) receptor. Furthermore, agonists at this site appear to augment some forms of learning in animal and human trials. The process of extinction of conditioned fear was initially shown to be facilitated by D-Cycloserine (DCS), an NMDA agonist, given in individual doses prior to extinction training in an animal model. There is growing evidence that a similar effect is found in human subjects undergoing controlled exposure therapy for specific phobia. This translational research proposal represents a randomized-control study with the goal of determining whether a drug that acutely enhances learning in both human and animal research will facilitate the extinction of fear that occurs with behavioral therapy for children with food aversion. Specifically, it is proposed that a single dose of DCS, given shortly before each of 5 days of behavioral therapy sessions utilizing escape extinction, will significantly enhance the rate of response and possibly the efficacy of treatment for pediatric food aversion. To this end, the investigators propose to enroll 16 participants with food aversion. Participants will be randomly assigned to receive behavioral intervention alone or in combination with 0.7mg/kg DCS. Behavioral ratings and outcomes will be assessed by independent assessors blind to subject condition. Participants will be assessed pre-treatment and at a one month follow-up session to assess long term effects.
• This type of combined treatment -- specific pharmacotherapeutic augmentation of behavioral therapy -- would be novel in pediatric populations with food aversion and would potentially be generalizable to many different forms of behavioral intervention for a wide range of pediatric disorders. The potential for detrimental health outcomes associated with feeding disorders, combined with their complex biopsychosocial etiology, intensifies the need to identify and refine effective treatments. If this translational research is successful, the ability of a relatively benign agent administered acutely before a behavioral therapy session to facilitate the extinction process could have important clinical, humanitarian, and economic advantages.

Specific Aims: The entire proposed study is designed to achieve the following specific aims:

1. To explore whether d-cycloserine (DCS), an NMDA partial agonist, facilitates extinction of food aversion in children using extinction based behavioral intervention.
2. To explore whether any facilitation in extinction produced by DCS in behavioral intervention evidenced within session and immediately post-treatment results in long-term gains in treatment response as compared to behavioral intervention alone.

2.2 Research Hypotheses: The following hypotheses will be tested:

1. DCS will facilitate extinction in children. It is predicted that the children who receive behavioral intervention combined with 0.7mg/kg DCS will evidence more rapid improvement in mealtime behavior (acceptance, swallowing, disruptions, expulsions, grams consumed) than children receiving behavioral intervention alone.
2. Facilitation in therapeutic response aided by DCS will result in long-term gains. It is predicted that the group of patients who receive behavioral intervention combined with 0.7 mg/kg DCS will evidence more improvement at the follow-up assessment as compared to baseline behavior (acceptance, swallowing, disruptions, expulsions, grams consumed) than the group who receives behavioral intervention alone.