Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome

Sponsor
Alexander Kolevzon (Other)
Overall Status
Completed
CT.gov ID
NCT02710084
Collaborator
(none)
18
1
2
51
0.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Piloting Treatment With Intranasal Oxytocin in Phelan-McDermid Syndrome
Study Start Date :
Apr 29, 2016
Actual Primary Completion Date :
Jul 29, 2020
Actual Study Completion Date :
Jul 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Oxytocin

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
Intranasal oxytocin
Other Names:
  • Syntocinon
  • Placebo Comparator: Saline

    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
    Placebo

    Outcome Measures

    Primary Outcome Measures

    1. Change in Aberrant Behavior Checklist [Baseline and Week 12]

      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.

    Secondary Outcome Measures

    1. Change in Visual Paired Comparison (VPC) Task [Baseline and Week 12]

      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.

    2. Change in Gap-Overlap Task [Baseline and Week 12]

      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.

    3. Change in Flicker Tasks [Baseline and Week 12]

      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.

    4. Change in Vineland Adaptive Behavior Scales [Baseline and Week 12]

      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.

    5. Change in Repetitive Behavior Scale-Revised (RBS-R) [Baseline and Week 12]

      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.

    6. Change in Clinical Global Impression - Severity Scales [Baseline and Week 12]

      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.

    7. Change in Short Sensory Profile (SSP) [Baseline and Week 12]

      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.

    8. Change in Macarthur-Bates Communicative Development Inventory (MCDI) [Baseline and Week 12]

      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.

    9. Change in EEG Tasks: Auditory Habituation [Baseline and Week 12]

      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.

    10. Number of Adverse Events [week 12]

      Number of Adverse Events through week 12

    11. Change in Caregiver Strain Index [Baseline and Week 12]

      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

    12. Change in Mullen Scales of Early Learning (MSEL) [baseline and 12 weeks.]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    5 Years to 17 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Icahn School of Medicine at Mount Sinai New York New York United States 10029

    Sponsors and Collaborators

    • Alexander Kolevzon

    Investigators

    • Principal Investigator: Alexander Kolevzon, MD, Icahn School of Medicine at Mount Sinai

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Alexander Kolevzon, Alexander Kolevzon, Clinical Director, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT02710084
    Other Study ID Numbers:
    • GCO 15-1223
    First Posted:
    Mar 16, 2016
    Last Update Posted:
    Dec 6, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Period Title: First Phase - 12 Weeks
    STARTED 10 8
    COMPLETED 7 7
    NOT COMPLETED 3 1
    Period Title: First Phase - 12 Weeks
    STARTED 7 7
    COMPLETED 7 7
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin Total
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin. Total of all reporting groups
    Overall Participants 10 8 18
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    9.8
    (3.6)
    6.8
    (1.4)
    8.4
    (3.2)
    Sex: Female, Male (Count of Participants)
    Female
    5
    50%
    4
    50%
    9
    50%
    Male
    5
    50%
    4
    50%
    9
    50%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Aberrant Behavior Checklist Social Withdrawal (ABC-SW) subscale (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    20.1
    (6.1)
    14.
    (3.4)
    17.4
    (5.9)
    Verbal DQ - developmental quotient (T-score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-score]
    14.9
    (12.8)
    26.4
    (21.3)
    20
    (17.6)
    Nonverbal DQ (T-score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-score]
    20.1
    (11.7)
    26.1
    (13.1)
    22.7
    (12.3)
    Full Scale DQ (T-score) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [T-score]
    17.4
    (11.8)
    26.3
    (16.7)
    21.4
    (14.5)

    Outcome Measures

    1. Primary Outcome
    Title Change in Aberrant Behavior Checklist
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    In the case of two participants who dropped out after week 4, difference scores were calculated for each outcome measure using the last observation carried forward (This is why some measures have N's of 9 and 7). Two participants dropped out after BL and were not included in the analysis.
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 9 7
    Social Withdrawal
    -7.44
    (4.58)
    -2.42
    (3.15)
    Irritability
    -5
    (6.63)
    -1.71
    (7.13)
    Stereotypy
    -2.22
    (4.66)
    0.57
    (2.99)
    Hyperactivity
    -8.11
    (11.85)
    -2.71
    (7.34)
    Inappropriate speech
    -1.67
    (3.04)
    -7.14
    (2.21)
    2. Secondary Outcome
    Title Change in Visual Paired Comparison (VPC) Task
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only 3 participants with data from baseline and week 12
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 1 2
    Social-Novel Preference
    0.01
    (NA)
    0.02
    (0.12)
    Nonsocial-Novel Preference
    -0.38
    (NA)
    0.22
    (0.12)
    3. Secondary Outcome
    Title Change in Gap-Overlap Task
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only 2 participants with data from both baseline and Week 12
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 2 0
    Mean (Standard Deviation) [milliseconds (ms)]
    63.81
    (34.19)
    4. Secondary Outcome
    Title Change in Flicker Tasks
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Only 1 participant with data from baseline and Week 12
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 0 1
    Preference for the Target Box at 0.2 Hz
    0.10
    (NA)
    Preference for the Target Box at 0.5 Hz
    0.30
    (NA)
    Preference for the Target Box at 1 Hz
    -0.12
    (NA)
    Preference for the Target Box at 2 Hz
    0.03
    (NA)
    5. Secondary Outcome
    Title Change in Vineland Adaptive Behavior Scales
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Participants were only included in this analysis if they had Vinelands at BL and Week 12. One incomplete Maladaptive subdomain form for one participant.
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 7 6
    Communication
    4
    (7.72)
    2.83
    (4.83)
    Daily Living Skills
    3.29
    (8.39)
    1.17
    (5.13)
    Socialization
    3
    (4.86)
    -0.5
    (4.46)
    Motor
    1
    (3.46)
    3.17
    (6.18)
    Adaptive Behavior Composite
    3.14
    (3.80)
    2
    (3.22)
    Internalizing
    -1.14
    (1.07)
    6
    (0.84)
    Externalizing
    -1.14
    (2.73)
    6
    (1.33)
    Maladaptive
    -1.33
    (2.42)
    6
    (0.55)
    6. Secondary Outcome
    Title Change in Repetitive Behavior Scale-Revised (RBS-R)
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Patients were only included in this analysis if they had RBS-R at BL and Week 12
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 9 7
    Stereotypic behaviors
    -1.67
    (2.78)
    0.29
    (2.87)
    Self-injury
    -1.22
    (3.11)
    1
    (2.31)
    Compulsive behaviors
    -1.56
    (3.09)
    -0.14
    (0.69)
    Ritualistic behaviors
    -1.33
    (2.40)
    -0.43
    (1.62)
    Sameness behaviors
    -2
    (2.65)
    -0.29
    (1.60)
    Restrictive behaviors
    -1.43
    (2.39)
    0.14
    (0.90)
    Overall Score
    -8.56
    (13.29)
    0
    (5.56)
    7. Secondary Outcome
    Title Change in Clinical Global Impression - Severity Scales
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Data from all participants who had data collected at 12 weeks.
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 9 7
    Mean (Standard Deviation) [score on a scale]
    -0.11
    (0.17)
    -0.1
    (0.24)
    8. Secondary Outcome
    Title Change in Short Sensory Profile (SSP)
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    In the case of two participants who dropped out after week 4, difference scores were calculated for each outcome measure using the last observation carried forward (This is why some measures have N's of 9 and 7). Two participants dropped out after BL and were not included in the analysis.
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 9 7
    Tactile
    2.56
    (5.17)
    1.57
    (3.78)
    Taste/Smell
    1.67
    (2.88)
    0.71
    (1.89)
    Movement
    -0.67
    (2.0)
    0.29
    (0.76)
    Under-responsive/seeks attention
    4.44
    (5.50)
    0.71
    (4.68)
    Auditory filtering
    4
    (5.68)
    0.29
    (5.21)
    Low energy/weak
    1.67
    (6.18)
    -0.71
    (4.19)
    Visual/auditory sensitivity
    1.89
    (2.57)
    -0.86
    (2.67)
    Summary total
    14.33
    (21.31)
    1
    (17.95)
    9. Secondary Outcome
    Title Change in Macarthur-Bates Communicative Development Inventory (MCDI)
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 7 7
    Phrases understood
    0.83
    (6.62)
    1.43
    (3.55)
    Words understood
    -9.17
    (52.59)
    7
    (13.41)
    Words produced
    11.67
    (41.90)
    2.57
    (10.23)
    Early gestures
    1.83
    (2.64)
    0.29
    (1.38)
    Later gestures
    3
    (7.48)
    0.86
    (1.95)
    Total gestures
    4.83
    (9.97)
    0.57
    (2.07)
    10. Secondary Outcome
    Title Change in EEG Tasks: Auditory Habituation
    Description 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.
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    Data results available only for those who underwent Auditory Habituation EEG task
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 2 1
    Auditory Habituation: N1 Habituation Change
    0.05
    (0.37)
    0.12
    (NA)
    Auditory Habituation: P2 Habituation Change
    1.15
    (0.91)
    -3.48
    (NA)
    11. Secondary Outcome
    Title Number of Adverse Events
    Description Number of Adverse Events through week 12
    Time Frame week 12

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study will follow a double-blind, placebo-controlled design. Participants randomized to the experimental group will receive intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU.
    Measure Participants 10 8
    Number [events]
    41
    35
    12. Secondary Outcome
    Title Change in Caregiver Strain Index
    Description 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
    Time Frame Baseline and Week 12

    Outcome Measure Data

    Analysis Population Description
    incomplete form for one participant
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 6 7
    Mean (Standard Deviation) [score on a scale]
    -1.83
    (1.47)
    -0.86
    (1.07)
    13. Secondary Outcome
    Title Change in Mullen Scales of Early Learning (MSEL)
    Description 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.
    Time Frame baseline and 12 weeks.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Saline Then Oxytocin Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received 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 received intranasal oxytocin, in identical doses. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. The second phase was a 12-week open-label extension phase during which all participants received intranasal oxytocin.
    Measure Participants 7 7
    Gross motor
    -1.57
    (4.69)
    -0.86
    (1.46)
    Visual Reception
    0.29
    (7.0)
    2.86
    (3.30)
    Fine Motor
    -0.29
    (1.11)
    0.71
    (1.80)
    Receptive Language
    -1.86
    (4.86)
    1.71
    (2.70)
    Expressive Language
    0.43
    (2.61)
    0.43
    (1.80)

    Adverse Events

    Time Frame through week 12
    Adverse Event Reporting Description Monitoring of adverse events (AEs) was done using an adapted semi-structured interview, the Safety and Monitoring Uniform Report Form (SMURF). AEs were documented with respect to severity, duration, management, relationship to study drug, and outcome. Severity was graded using a scale of mild, moderate, or severe.
    Arm/Group Title Saline Intranasal Oxytocin
    Arm/Group Description During the first phase, patients randomized to the placebo group received intranasal saline solution in doses of 24 IU two times daily, for a total of 48 IU. The first phase of the study followed a double-blind, placebo-controlled design. Participants randomized to the experimental group received intranasal oxytocin started the trial with a dose of 24 international units (IU) twice daily (BID), which was adjusted to 12 IU BID, subsequently the dose was increased to 24IU BID. Each insufflation delivered 4 IU and three insufflations (12 IU) in each nostril were given twice daily for a total daily dose of 48 IU. During the second phase of the study, all participants received oxytocin, in identical doses.
    All Cause Mortality
    Saline Intranasal Oxytocin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 15/15 (100%)
    Serious Adverse Events
    Saline Intranasal Oxytocin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/10 (0%) 0/15 (0%)
    Other (Not Including Serious) Adverse Events
    Saline Intranasal Oxytocin
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 9/10 (90%) 15/15 (100%)
    Ear and labyrinth disorders
    Rubbing ears 1/10 (10%) 0/15 (0%)
    Endocrine disorders
    Hirsutism 0/10 (0%) 1/15 (6.7%)
    Gastrointestinal disorders
    Diarrhea 1/10 (10%) 2/15 (13.3%)
    Tooth pain 0/10 (0%) 1/15 (6.7%)
    General disorders
    Sedation 2/10 (20%) 1/15 (6.7%)
    Periorbital / facial swelling 1/10 (10%) 1/15 (6.7%)
    Sleep disturbance 2/10 (20%) 7/15 (46.7%)
    Fever 4/10 (40%) 9/15 (60%)
    Leg weakness 1/10 (10%) 1/15 (6.7%)
    Bloody nose 0/10 (0%) 3/15 (20%)
    Foot pain 1/10 (10%) 0/15 (0%)
    Infections and infestations
    Upper respiratory tract infection 1/10 (10%) 2/15 (13.3%)
    Infection 3/10 (30%) 6/15 (40%)
    Injury, poisoning and procedural complications
    Accidental injury 1/10 (10%) 0/15 (0%)
    Metabolism and nutrition disorders
    Decreased appetite 2/10 (20%) 0/15 (0%)
    Increased appetite 1/10 (10%) 1/15 (6.7%)
    Nervous system disorders
    Seizure 1/10 (10%) 0/15 (0%)
    Psychiatric disorders
    Irritability/agitation 3/10 (30%) 3/15 (20%)
    Aggression/self-injury 1/10 (10%) 2/15 (13.3%)
    Elated mood/Silliness 1/10 (10%) 5/15 (33.3%)
    Restlessness/hyperactivity 1/10 (10%) 8/15 (53.3%)
    Stereotypies 2/10 (20%) 4/15 (26.7%)
    Apathy 0/10 (0%) 1/15 (6.7%)
    Disinhibited 1/10 (10%) 1/15 (6.7%)
    Oppositional behavior 3/10 (30%) 2/15 (13.3%)
    Low frustration tolerance 1/10 (10%) 3/15 (20%)
    Tantrums 0/10 (0%) 1/15 (6.7%)
    Renal and urinary disorders
    Enuresis 1/10 (10%) 1/15 (6.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/10 (0%) 2/15 (13.3%)
    Runny nose/congestion 1/10 (10%) 1/15 (6.7%)
    Allergies/asthma 2/10 (20%) 3/15 (20%)
    Skin and subcutaneous tissue disorders
    Eczema 1/10 (10%) 3/15 (20%)

    Limitations/Caveats

    The small sample size, potential challenges with drug administration, and expectancy bias due to relying on parent reported outcome measures may all contribute to limitations in interpreting results.

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Alexander Kolevzon, MD
    Organization Icahn School of Medicine at Mount Sinai
    Phone 212-659-9134
    Email alexander.kolevzon@mssm.edu
    Responsible Party:
    Alexander Kolevzon, Alexander Kolevzon, Clinical Director, Icahn School of Medicine at Mount Sinai
    ClinicalTrials.gov Identifier:
    NCT02710084
    Other Study ID Numbers:
    • GCO 15-1223
    First Posted:
    Mar 16, 2016
    Last Update Posted:
    Dec 6, 2021
    Last Verified:
    Dec 1, 2021