Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome

Study Overview
=================
Brief Summary
-----------------
This is a pilot study examining the efficacy, safety and tolerability of intranasal oxytocin as a novel treatment in Phelan-McDermid syndrome (PMS). This study will utilize a randomized, placebo-controlled design for 12 weeks (phase 1), followed by an open-label extension for 12 weeks (phase 2). The purpose is to evaluate the effect of intranasal oxytocin on impairments in attention, social memory, socialization, language, and repetitive behaviors.

Official Title
-----------------
Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome

Conditions
-----------------
Phelan-McDermid Syndrome

Intervention / Treatment
-----------------
* Drug: Oxytocin
* Drug: Saline


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Have a diagnosis of Phelan-McDermid syndrome defined by pathogenic deletion or mutation of the SHANK3 gene and confirmed by chromosomal microarray or sequencing. Must be between the ages of 5 and 17 Must be on stable medication and psychosocial therapy regimens for at least three months prior to enrollment Exclusion criteria: Allergy to oxytocin Active cardiovascular disease, epilepsy, or renal disease that is not controlled by medication Pregnant, lactating or refuse to practice contraception if sexually active Have caretakers who are unable to speak English, be consistently present at visits to report on symptoms, or are otherwise judged unable to comply with the protocol by the study team Comorbid conditions such that the patient is too medically compromised to participate

Ages Eligible for Study
-----------------
Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxytocin<br>The first phase of the study will follow a double-blind, placebo-controlled design. Participants randomized to the experimental group will receive intranasal oxytocin in doses of 24 IU, two times daily, for a total of 48 IU. Doses may be reduced by 8 IU/day if safety concerns emerge. During the second phase of the study, all participants will receive oxytocin, in identical doses. | Drug: Oxytocin<br>* Intranasal oxytocin<br>* Other names: Syntocinon;|
| Placebo Comparator: Saline<br>During the first phase, patients randomized to the placebo group will receive intranasal saline solution in doses of 24 IU two times daily, for a total of 48 IU. During the second phase of the study, all participants will receive oxytocin, in identical doses. | Drug: Saline<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aberrant Behavior Checklist | Change in scale at week 12 as compared to baseline. Aberrant Behavior Checklist - behavior rating subscales for the assessment of treatment effects.16 items, Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Total score range from 0 to 48, with higher score indicating poorer health outcomes. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Paired Comparison (VPC) Task | Change in VPC Task has 2 subscores at week 12 as compared to baseline. The subject is initially presented with a target for familiarization and the familiar target is then paired with a novel target. Recognition is indexed by a novelty score derived from the percentage of time looking at the novel stimulus vs. the familiar stimulus. The Social-Novel Preference score refers to the proportion of time spent looking at novel stimuli out of all the time spent looking at both novel and familiar stimuli in the social test. The Nonsocial-Novel Preference score refers to the proportion of time spent looking at novel stimuli out of all the time spent looking at both novel and familiar stimuli in the nonsocial test.The scores are given in proportions with a range from -1 to 1. A score of -1 would mean the participant shows a preference for familiar stimuli and a score of 1 demonstrates a preference for novel stimuli. | Baseline and Week 12 | 
| Change in Gap-Overlap Task | One of three computerized eye tracking tasks to measure attention. three computer screens are set up side by side. A stimulus initially appears on the central screen, and once the participant orients to that stimulus, another stimulus will appear on one of the lateral screens. In the gap condition, the central stimulus will disappear before the peripheral stimulus appears. In the overlap condition, the central stimulus will remain on the screen while the peripheral stimulus appears. In both conditions, reaction times of the participant's eye movements (saccadic reaction time) from the central stimulus to the peripheral stimulus will be measured. Gap Effect measures the difference between average Gap and Overlap saccade latencies. | Baseline and Week 12 | 
| Change in Flicker Tasks | One of three computerized eye tracking tasks to measure attention. The flicker task, or the four-alternative forced-choice preferential looking paradigm - the time interval over which the visual system is able to parse information. Scores range from -1 to 1 with higher scores indicating better (more typical) performance. | Baseline and Week 12 | 
| Change in Vineland Adaptive Behavior Scales | Mean change in scale at week 12 as compared to baseline. Vineland Adaptive Behavior Communication Domain measures adaptive functioning. Vineland-II subdomains (Communication, Daily Living Skills, Socialization, Motor, Adaptive Behavior Composite, Internalizing, Externalizing and maladaptive) are V-scale scores (M=15, SD=3). Higher scores indicate better developed adaptive social behavior. Vineland-II domain and composite values are standard scores (M=100, SD=15). Higher scores indicate better developed adaptive social behavior. | Baseline and Week 12 | 
| Change in Repetitive Behavior Scale-Revised (RBS-R) | Change in Repetitive Behavior Scale at week 12 as compared to baseline. the RBS-R is a 44-item self-report questionnaire consisting of subscales and one additional global rating score from 1-100. Score range for Stereotypic Behavior subscale is 0-27, Self-Injurious Behavior subscale is 0-24, Compulsive Behavior subscale is 0-18, Ritualistic/Sameness Behavior subscale is 0-36, and Restricted Interests subscale 0-9. Total scale for RBS-R is 0-214, with higher score indicating more severe problem. | Baseline and Week 12 | 
| Change in Clinical Global Impression - Severity Scales | Mean Change in Clinical Global Impression-Severity Scales at week 12 as compared to baseline. Clinical Global Impressions (CGI) Rating Scales are commonly used to measure symptom severity and global improvement in treatment studies of patients with developmental disorders. There Severity Scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of illness at the time of assessment. Full scale from 1 - 7. Higher scores indicate greater symptom severity. | Baseline and Week 12 | 
| Change in Short Sensory Profile (SSP) | Mean Change in Short Sensory Profile Scale at week 12 as compared to baseline, measuring sensory sensitivity and sensory seeking behavior. The SSP is a 38-item caregiver questionnaire. Items are based on a 5-point Liker scale ranging from 1=always to 5=never. Tactile Sensitivity ranges from 7-35. Taste/Smell Sensitivity ranges from 4-20. Movement Sensitivity ranges from 3-15. Underresponsive/Seeks Sensation ranges from 7-35. Auditory Filtering ranges from 6-30. Low Energy/Weak ranges from 6-30. Visual/Auditory Sensitivity ranges from 5-25. Total scale range from 38-190. Lower scores indicate a higher probability of sensory processing abnormalities. | Baseline and Week 12 | 
| Change in Macarthur-Bates Communicative Development Inventory (MCDI) | Macarthur-Bates Communicative Development Inventory at week 12 as compared to baseline, measuring language. Words and Gestures Forms are for children ages 8-18 months. In the form, the first part prompts parents to document the child's understanding of hundreds of early vocabulary items separated into semantic categories such as animal names, household items, and action words. Parents mark the words understood or used, and the forms yield separate indexes of words understood and words produced. The second part of each form asks parents to record the communicative and symbolic gestures the child has tried or completed. Ranges for each subscale score are as follows: Phrases understood (0-28), Words understood (0-396), Words produced (0-396), Early gestures (0-18), Later gestures (0-45), Total gestures (0-63). Higher scores indicate a great number of words, phrases, or gestures understood or produced. | Baseline and Week 12 | 
| Change in EEG Tasks: Auditory Habituation | In the Auditory Habituation EEG task, participants listen to a series of 4 tones and the neural responses to each of these tones (event related potentials, ERPs ) are averaged. The N1 and P2 components are typical responses to auditory stimuli. The N1 response is the initial, quick response to hearing a stimulus, and P2 reflects the later processing of the stimulus. Both of these should be greater in response to the first tone, and then reduce in response to each subsequent tone. This is known as habituation, and is calculated as the change in Tone 1 minus Tone 2 response for both N1 and P2 components. | Baseline and Week 12 | 
| Number of Adverse Events | Number of Adverse Events through week 12 | week 12 | 
| Change in Caregiver Strain Index | Mean Change Caregiver Strain Index at week 12 as compared to baseline. The Caregiver Strain Questionnaire is a 21-item measure of self-reported strain experienced by caregivers and families of youth with emotional problems, with responses on a 5-point Likert scale (0 = Not at all, 4 = very much). Full scale from 0 to 84, higher score indicates higher caregiver burden | Baseline and Week 12 | 
| Change in Mullen Scales of Early Learning (MSEL) | Change in Mullen Scales of Early Learning (MSEL) at week 12 as compared to baseline. The Mullen Scales results are reported using Age Equivalents, which provides an estimate of the chronological age (CA) in years and months at which a typically developing child demonstrates the skills displayed by the child being assessed. The Mullen Scales results are reported using T scores. (M = 100, SD = 15). Each subscale is standardized to calculate an age-equivalent score. Higher scores represent a higher CA, and therefore better outcome. | baseline and 12 weeks. |