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Clinical Trial in 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01525901
Recruitment Status : Completed
First Posted : February 3, 2012
Results First Posted : May 12, 2022
Last Update Posted : May 12, 2022
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Alexander Kolevzon, Icahn School of Medicine at Mount Sinai

Brief Summary:
The purpose of this study is to pilot the use of Insulin-Like Growth Factor-1 (IGF-1) treatment in 22q13 Deletion Syndrome (Phelan-McDermid Syndrome) caused by SHANK3 gene deficiency in order to evaluate safety, tolerability, and efficacy. IGF-1 is an injection under the skin that contains human IGF-1. IGF-1 is approved by the FDA under the brand name Increlex for the treatment of children with short stature due to primary IGF-1 deficiency. It is being used off-label in the current study and is not FDA approved, nor has it yet been studied in humans for the treatment of SHANK3 deficiency.

Condition or disease Intervention/treatment Phase
22q13 Deletion Syndrome Phelan-McDermid Syndrome Drug: Insulin-Like Growth Factor-1 (IGF-1) Drug: Normal saline Phase 2

Detailed Description:

Overall, there will be 1-3 screening visits, a baseline visit where study drug will first be administered, and then 10 follow-up visits. Follow-up visits will occur at week 2, week 4, week 8, and week 12 in each treatment phase (IGF-1 or placebo), and then again 4 weeks after study completion, Parents/guardians will be asked to administer the IGF-1/ placebo by injection at home and will also be responsible for monitoring glucose levels in the child. Parents/guardians will be trained in these methods, and will have scheduled phone calls and appointments where the dose and tolerability will be discussed.

Assessments include the following:

  • Physical and neurological examination
  • Medical and psychiatric history
  • X-ray of long bone (e.g., hand) to ensure your child's growth plates are not closed
  • Electrocardiography
  • Echocardiography
  • Pregnancy test if applicable
  • Lab safety measures (through blood draw)
  • Autism Diagnostic Interview (ADI)
  • Autism Diagnostic Observation Schedule (ADOS)
  • The Mullen Scales of Early Learning or the Leiter International Performance Scale-Revised
  • Vineland Adaptive Behavior Scale (VABS)
  • Clinical Global Impressions (CGI) Rating Scales
  • The Repetitive Behaviors Scale (RBS)
  • Aberrant Behavior Checklist (ABC)
  • The Caregiver Strain Questionnaire (CSI)
  • Language Environment Analysis (LENA)
  • The Macarthur-Bates Communication Inventory (MCDI)
  • Unified Parkinson's Disease Rating Scale (UPDRS)
  • Quick Neurological Screening Test 2nd Edition (QNST-2)
  • Gait Analysis with motion capture video systems and interactive 3-dimensional modeling systems

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 19 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-Blind Placebo-Controlled Crossover Trial of Insulin-Like Growth Factor-1 (IGF-1) in Children and Adolescents With 22q13 Deletion Syndrome(Phelan-McDermid Syndrome)
Study Start Date : February 2012
Actual Primary Completion Date : August 23, 2016
Actual Study Completion Date : August 23, 2016


Arm Intervention/treatment
Experimental: Insulin-Like Growth Factor-1 (IGF-1)
Injection
Drug: Insulin-Like Growth Factor-1 (IGF-1)
IGF-1 and placebo will each be administered for 3 months with a four-week washout period in between. IGF-1 will be administered for 3 months subcutaneously.
Other Name: Mecasermin; Increlex

Placebo Comparator: Normal saline
Injection
Drug: Normal saline
Saline solution will be administered for three months subcutaneously.
Other Name: Placebo




Primary Outcome Measures :
  1. Change in Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) Subscale - Study 1 [ Time Frame: Baseline and Week 12 ]
    16 items on ABC-SW subscale, Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Total score from 0 to 48 with higher score indicating poorer health outcomes.

  2. Change in Aberrant Behavior Checklist - Social Withdrawal (ABC-SW) Subscale Study 2 [ Time Frame: Baseline and Week 12 ]
    16 items on ABC-SW subscale, Each item is scored as 0 (never a problem), 1 (slight problem), 2 (moderately serious problem), or 3 (severe problem). Total score from 0 to 48 with higher score indicating poorer health outcomes..


Secondary Outcome Measures :
  1. Change in Repetitive Behavior Scale - Study 2 [ Time Frame: Baseline and Week 12 ]

    Repetitive Behavior Scale (RBS) - Total Score 43 items, each item scored on 4-point scale: 0-Behavior does not occur, 1-Behavior occurs and is a mild problem, 2-Behavior occurs and is a moderate problem, 3-Behavior occurs and is a severe problem. with total score from 0 (mild) to 129 (severe).

    The subscales are stereotyped behaviors 6 items (subscale 0-18), self-injurious behaviors 8 items (subscale 0-24), Compulsive behaviors- 8 items (subscale 0-24), Ritualistic Behaviors 6 items (subscale from 0-18), Sameness 11 items (subscale 0-33), restricted behaviors 4 items (subscale 0-12). Total score is the sum of all items in the subscale with total score range from 0 to 129. Higher scores indicate greater symptom severity.


  2. Change in CGI-Improvement and Severity Scales; - Study 2 [ Time Frame: Baseline and Week 12 ]

    The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.

    The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse.


  3. Change in Caregiver Strain Questionnaire [ Time Frame: Baseline and Week 12 ]
    21 question tool, about caregiver strain, where each question uses a Likert scale where 1 is "Not at all" and 5 is "Very much." The full scale ranges from 21-105, where higher scores indicate more severe strain.

  4. Change in Sensory Profile (SP) - Study 2 [ Time Frame: Baseline and Week 12 ]

    The SP is a standardized parent-completed questionnaire that assesses sensory processing and its impact on the functioning of children ages 3-10 yr. The 125 items represent behaviors that can be interpreted as responses to sensory experiences. The parent rates the observed frequency of these behaviors on a 5-point Likert scale (ranging from 1 always to 5 never). The tool consists of 14 sections, listed below, that refer to sensory processing, modulation, and behavioral and emotional responses. Subscale scores are listed below.

    Each section's raw score is compared with a threshold value to determine a category of performance: typical performance, probable difference (1 standard deviation below the mean), and definite difference (2 standard deviations below the mean). A lower raw score means a greater difference.


  5. Change in Short Sensory Profile (SSP) - Study 2 [ Time Frame: Baseline and 12 weeks ]

    The Short Sensory Profile is a caregiver report measure consisting of 38 items, each scored on a 1-point (always) to 5-point (never) Likert scale.

    SSP Subscales Tactile Sensitivity (7 to 35) Taste/Smell Sensitivity (4 to 20), Movement Sensitivity (3 to 15), Under-Responsive/Seek Sensation (7 to 35) , Auditory Filtering (6 to 30), Low Energy/Weak (6 to 30), Visual/Auditory Sensitivity (5 to 25), with total scale from (38 to 190)

    Lower scores indicate more sensory alterations.




Information from the National Library of Medicine

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Ages Eligible for Study:   5 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 5 to 12 years old
  • pathogenic deletions or mutations of the SHANK3 gene
  • stable medication regimens for at least three months prior to enrollment

Exclusion Criteria:

  • closed epiphyses
  • active or suspected neoplasia
  • intracranial hypertension
  • hepatic insufficiency
  • renal insufficiency
  • cardiomegaly / valvulopathy
  • history of allergy to IGF-1 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 deemed too medically compromised to tolerate the risk of experimental treatment with IGF-1

Information from the National Library of Medicine

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): NCT01525901


Locations
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United States, New York
Seaver Austin Center, Icahn School of Medicine at Mount Sinai
New York, New York, United States, 10029
Sponsors and Collaborators
Icahn School of Medicine at Mount Sinai
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Alexander Kolevzon, MD Icahn School of Medicine at Mount Sinai
  Study Documents (Full-Text)

Documents provided by Alexander Kolevzon, Icahn School of Medicine at Mount Sinai:
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alexander Kolevzon, Principal Investigator, Icahn School of Medicine at Mount Sinai
ClinicalTrials.gov Identifier: NCT01525901    
Other Study ID Numbers: GCO 12-0929
IF# 1358648
1R34MH100276-01 ( U.S. NIH Grant/Contract )
GCO 11-1555 ( Other Identifier: Icahn School of Medicine at Mount Sinai )
R34MH100276 ( U.S. NIH Grant/Contract )
First Posted: February 3, 2012    Key Record Dates
Results First Posted: May 12, 2022
Last Update Posted: May 12, 2022
Last Verified: April 2022
Keywords provided by Alexander Kolevzon, Icahn School of Medicine at Mount Sinai:
SHANK3
IGF-1
Autism
Additional relevant MeSH terms:
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Chromosome Disorders
Syndrome
Chromosome Deletion
Disease
Pathologic Processes
Monosomy
Aneuploidy
Chromosome Aberrations
Congenital Abnormalities
Genetic Diseases, Inborn
Mitogens
Mecasermin
Physiological Effects of Drugs
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances