Phelan McDermid Syndrome Clinical Trial
Official title:
An Open Label Trial of Growth Hormone in Children and Adolescents With Phelan-McDermid Syndrome Targeting Social Withdrawal
| Verified date | April 2024 |
| Source | Icahn School of Medicine at Mount Sinai |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Phelan McDermid syndrome (PMS) is a rare genetic form of autism spectrum disorder (ASD) due to deletions or mutations in the SHANK3 gene. This is a pilot open labeled trial of growth hormone therapy in children with PMS targeting social withdrawal and repetitive behavior. This research study will include children with PMS between 2-12 years of age who will receive growth hormone daily for 12 weeks, if found to be eligible. The aim of this study is to evaluate the effect of growth hormone on behavioral outcomes such as the aberrant behavior checklist social withdrawal subscale (ABC-SW) and repetitive behavior scale- revised (RBS-R). The effects of growth hormone on visual evoked potentials will also be assessed. Growth hormone increases insulin like growth factor 1 (IGF-1) levels and a previous trial of IGF-1 therapy in PMS children showed improvement in these behavioral scales. Growth hormone has been studied for decades with an excellent safety profile and fewer adverse effects compared to IGF-1 therapy in other conditions. Hence, this may be a viable therapeutic option. There is no treatment currently available for PMS and this trial is therefore extremely important.
| Status | Completed |
| Enrollment | 6 |
| Est. completion date | June 5, 2020 |
| Est. primary completion date | June 5, 2020 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 2 Years to 12 Years |
| Eligibility | Inclusion Criteria: - Known pathogenic deletions or mutations in SHANK3 gene diagnosed by array CGH and/or direct sequencing. - Children between 2 and 12 years of age. - Open epiphyses on bone age x ray Exclusion Criteria: - closed epiphyses; - active or suspected neoplasia; - intracranial hypertension; - hepatic insufficiency; - renal insufficiency; - cardiomegaly/valvulopathy; - history of allergy to growth hormone or any component of the formulation (mecasermin); - history of extreme prematurity (<1000 grams) with associated early neo-natal complications, e.g. intra-cerebral - hemorrhage, prolonged hypoxia, prolonged hypoglycemia; - patients with comorbid conditions who are deemed too medically compromised to tolerate the risk of experimental treatment with growth hormone. - Patient with visual problems that preclude the use of VEP's |
| Country | Name | City | State |
|---|---|---|---|
| United States | Seaver Autism Center | New York | New York |
| Lead Sponsor | Collaborator |
|---|---|
| Swathi Sethuram |
United States,
Aramburo C, Alba-Betancourt C, Luna M, Harvey S. Expression and function of growth hormone in the nervous system: a brief review. Gen Comp Endocrinol. 2014 Jul 1;203:35-42. doi: 10.1016/j.ygcen.2014.04.035. Epub 2014 May 13. — View Citation
Costales J, Kolevzon A. The therapeutic potential of insulin-like growth factor-1 in central nervous system disorders. Neurosci Biobehav Rev. 2016 Apr;63:207-22. doi: 10.1016/j.neubiorev.2016.01.001. Epub 2016 Jan 15. — View Citation
De Rubeis S, Siper PM, Durkin A, Weissman J, Muratet F, Halpern D, Trelles MDP, Frank Y, Lozano R, Wang AT, Holder JL Jr, Betancur C, Buxbaum JD, Kolevzon A. Delineation of the genetic and clinical spectrum of Phelan-McDermid syndrome caused by SHANK3 point mutations. Mol Autism. 2018 Apr 27;9:31. doi: 10.1186/s13229-018-0205-9. eCollection 2018. — View Citation
Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society. Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. Horm Res Paediatr. 2016;86(6):361-397. doi: 10.1159/000452150. Epub 2016 Nov 25. — View Citation
Kolevzon A, Bush L, Wang AT, Halpern D, Frank Y, Grodberg D, Rapaport R, Tavassoli T, Chaplin W, Soorya L, Buxbaum JD. A pilot controlled trial of insulin-like growth factor-1 in children with Phelan-McDermid syndrome. Mol Autism. 2014 Dec 12;5(1):54. doi: 10.1186/2040-2392-5-54. eCollection 2014. Erratum In: Mol Autism. 2015;6:31. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | ABC - Social Withdrawal Subscale | 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. | After 12 weeks of growth hormone therapy | |
| Primary | Repetitive Behavior Scale-Revised (RBS-R) | A 43 item instrument with total score from 0-129, with higher score indicating more restricted, repetitive and stereotyped behaviors. Subscales Stereotyped Behavior (0-27) Self-injurious Behavior (0-24) Compulsive Behavior (0-18) Ritualistic Behavior (0-36) Sameness Behavior (0-33) Restricted Behavior (0-12) |
After 12 weeks of growth hormone therapy | |
| Primary | The Sensory Profile | The full Sensory Profile has 125 items and the short version contains 38 items. 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. Subscales Tactile (7-35) Taste / Smell (4-20) Movement (3-15) Sensation (7-35) Auditory (6-30) Low Energy / Weak (6-30) Visual / Auditory (5-25) |
After 12 weeks of growth hormone therapy | |
| Primary | The Sensory Assessment for Neurodevelopmental Disorders (SAND) | 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. | After 12 weeks of growth hormone therapy | |
| Secondary | Visual Evoked Potentials (VEP) | 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. | After 12 weeks of growth hormone therapy | |
| Secondary | Change in Auditory Event Related Potentials (AERP) | 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. | Baseline and 12 weeks of growth hormone therapy |