Growth Hormone Treatment in Children With Phelan McDermid Syndrome
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|ClinicalTrials.gov Identifier: NCT04003207|
Recruitment Status : Completed
First Posted : July 1, 2019
Last Update Posted : June 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Phelan McDermid Syndrome||Drug: Recombinant human Growth hormone||Phase 2|
BACKGROUND: Phelan-McDermid syndrome (PMS) is a genetic form of autism spectrum disorder (ASD) associated with developmental delay and hypotonia. IGF-1 promotes brain vessel growth, neurogenesis, and synaptogenesis.
The research team previous clinical trial of IGF-1 in patients with Phelan McDermid Syndrome has shown improvement in core ASD symptoms using the Aberrant Behavior Checklist (ABC) and the Repetitive Behavior Scale-Revised (RBS-R). Growth hormone (GH) binds to its receptor and initiates a cascade of events which directly increases synthesis and release of IGF-1 levels. HYPOTHESIS: The study team hypothesize that rise in IGF-1 stimulated by growth hormone (GH) administration should produce improvement in behavior in children and adolescents with PMS as previously demonstrated with use of IGF-1.
RESEARCH PLAN: The study team seek to recruit 10 patients with PMS and administer growth hormone as once daily subcutaneous injections for 12 weeks at standard doses. The study team will monitor baseline anthropometric measures, laboratory parameters for growth, IGF-1 levels, and bone age prior to therapy and continue to monitor safety laboratory parameters during and after therapy. The goal of therapy would be to maintain IGF-1 levels between 1-2SD above the mean for age and puberty. Evaluations will include validated behavioral scales. Visual evoked potentials (VEPs) will be used as biomarkers of visual sensory reactivity.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||6 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal|
|Actual Study Start Date :||September 13, 2019|
|Actual Primary Completion Date :||June 5, 2020|
|Actual Study Completion Date :||June 5, 2020|
Experimental: Phelan-McDermid syndrome
Patients with Phelan-McDermid syndrome receive 12 weeks of growth hormone therapy
Drug: Recombinant human Growth hormone
Subcutaneous growth hormone injections given once daily at a dose between 0.15mg/kg/week to 0.47 mg/kg/week titrated based on IGF-1 levels in serum for a duration of 12 weeks.
- ABC - Social Withdrawal subscale [ Time Frame: After 12 weeks of growth hormone therapy ]A caregiver report symptom checklist. 58-item instrument into 5 subscales: Irritability (score 0-45); Lethargy/Social Withdrawal (score 0-48); Stereotypic Behavior (score 0-21); Hyperactivity (score 0-48); Inappropriate Speech (score 0-12). Total scale 0-174, with higher score indicating more aberrant behavior.
- Repetitive Behavior Scale-Revised (RBS-R) [ Time Frame: After 12 weeks of growth hormone therapy ]A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors.
- The Sensory Profile [ Time Frame: After 12 weeks of growth hormone therapy ]The full Sensory Profile has 125 items and the short version contains 38 items. Irritability; Lethargy/Social Withdrawal; Stereotypic Behavior; Hyperactivity; Inappropriate Speech. Parents use a Likert scale to rate how frequently their child demonstrates a particular behavior (ranging from 1 = always to 5 = never). Total scale for the Short Sensory Profile 38-190, with a lower score indicates greater deviation from typically developing children and indicates more sensory reactivity symptoms.
- The Sensory Assessment for Neurodevelopmental Disorders (SAND) [ Time Frame: After 12 weeks of growth hormone therapy ]a clinician-administered assessment and corresponding caregiver interview that is not dependent on verbal or cognitive ability and is therefore appropriate for severely affected or nonverbal individuals with PMS. Responses are rated by a trained examiner on an algorithm. Scores are dichotomous, 0 (not present) or 1 (present) and are based on a summary of observed sensory behaviors throughout the duration of the observation. A total SAND score ranging from 0 to 90. Higher scores represent a higher level of sensory reactivity symptoms.
- Visual evoked potentials (VEP) [ Time Frame: After 12 weeks of growth hormone therapy ]A noninvasive technique to evaluate the functional integrity of visual pathways in the brain from the retina to the visual cortex via the optic nerve/optic radiations. The VEP is recorded from the head's surface, over the visual cortex, and is extracted from ongoing EEG through signal averaging. VEPs reflect the sum of excitatory and inhibitory postsynaptic potentials occurring on apical dendrites (Zemon et al., 1986) which modulate excitatory and inhibitory signals received by the pyramidal cells.
- Change in Auditory event related potentials (AERP) [ Time Frame: Baseline and 12 weeks of growth hormone therapy ]AERP is useful for characterizing early processing of auditory tones and habituation to rapidly repeated stimuli as in speech processing. AERP amplitudes are measured at 12 weeks and compared to baseline.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04003207
|United States, New York|
|Seaver Autism Center|
|New York, New York, United States, 10029|
|Principal Investigator:||Swathi Sethuram, MD||Icahn School of Medicine at Mount Sinai|
|Study Director:||Alexander Kolevzon, MD||Icahn School of Medicine at Mount Sinai|
|Study Director:||Robert Rapaport, MD||Icahn School of Medicine at Mount Sinai|