Understanding how genetics affect growth hormone treatment in children with unknown short stature

A Study of the Genetic Determinants of Response to Growth Hormone Treatment in Children With Idiopathic Short Stature

This study is trying to see how genetics might affect how well growth hormone treatment works for children with unknown short stature who have been on the therapy for at least a year.

Quick facts

• Study type: Observational
• Enrollment: 700 (estimated)
• Ages: 3 Years to 11 Years
• Sex: All
• Sponsor: Novo Nordisk A/S (Industry-sponsored)
• Locations: 2 sites (Columbia, Maryland and 1 other locations)
• Trial ID: NCT05894876 on ClinicalTrials.gov

What this trial studies

This observational study aims to collect genetic information from children diagnosed with Idiopathic Short Stature who have undergone at least one year of growth hormone therapy before puberty. The researchers will analyze the genetic differences between participants who responded well to the treatment and those who did not. Participants will attend their usual doctor's appointments, and the study will last for up to one year, focusing on understanding the genetic basis of treatment response without providing any additional medications. Consent will be obtained from participants or their guardians before any study-related activities.

Who should consider this trial

Good fit: Ideal candidates are children aged 3 to 11 years for boys and 3 to 10 years for girls, diagnosed with Idiopathic Short Stature who have received at least one year of growth hormone therapy.

Not a fit: Patients who have previously received growth-promoting therapies or who do not meet the age and diagnosis criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to personalized growth hormone treatments based on genetic profiles, improving outcomes for children with Idiopathic Short Stature.

How similar studies have performed: While this approach is relatively novel, previous studies have explored genetic factors in treatment responses, indicating potential for success in understanding growth hormone therapy.

Eligibility criteria

Inclusion Criteria:

* Signed consent/parental consent and patient assent for minor children obtained before any study-related activities (study-related activities are any procedure related to recording of data according to the protocol).
* Patient has been diagnosed with Idiopathic Short Stature (ISS) and received at least 1 year of GH therapy.
* Patient was prepubertal at initiation of and throughout first year of GH therapy, as determined by the treating physician and patient medical records.
* Patient had no prior exposure to growth promoting therapy prior to initiation of GH therapy, including but not limited to growth hormone, IGF-I and ghrelin analogues.
* Age at initiation of GH therapy:

  * Boys: Age above or equal to 3 years and below 11.0 years.
  * Girls: Age above or equal to 3 years and below 10.0 years.
* Impaired height prior to initiation of GH therapy defined as at least 2 standard deviations below the mean height for chronological age and sex according to local growth reference charts. In the absence of local reference charts, the standards of Centres for Disease Control and Prevention should be used.
* GH deficiency has been excluded via GH stimulation test (cut point of 7 nanograms per milliliter \[ng/ml\]) or other clinical and biochemical criteria according to local clinical practice.
* Patient fits within one of the following response groups:

  * Change in Height Standard Deviation Score (SDS) after approximately the first year (+/- 2 months) of GH therapy greater than (\>) 1.0.
  * Change in Height SDS after approximately the first year (+/- 2 months) of GH therapy less than (\<) 0.4.

Exclusion Criteria:

* Previous participation in this study. Participation is defined as having given informed consent in this study.
* Mental incapacity, unwillingness or language barriers precluding adequate understanding, cooperation or informed consent.
* Receipt of any investigational medicinal product within 3 months before or during the first year of GH therapy that could influence response to GH therapy.
* Concomitant illness within 3 months before or during the first year of GH therapy that could (positively or negatively) influence the first year of GH therapy. Exception: Attention Deficit Hyperactive Disorder and its treatment can be included but should be recorded.
* Children with suspected or confirmed growth hormone deficiency according to local practice.
* Concomitant use of medication including gonadotropin-releasing hormone (GnRH) analogues, aromatase inhibitors, sex steroids, glucocorticoids or any other medication that can influence response to GH therapy. Exception: Attention Deficit Hyperactive Disorder and its treatment can be included but should be recorded.
* Any known or suspected clinically significant abnormality likely to affect growth or the ability to evaluate growth with standing height measurements, such as but not limited to:

  * Significant spinal abnormalities including but not limited to scoliosis, kyphosis and spina bifida variants.
  * Any other disorder that can cause short stature such as, but not limited to, psychiatric disorders, nutritional disorders, chronic systemic illness, chronic respiratory conditions (e.g. asthma), and chronic renal disease.
  * Turner Syndrome (including mosaicism).
  * Noonan Syndrome.
  * Born small for gestational age (defined as birth length below -2 SDS OR birth weight below -2 SDS OR both) (according to national standards).
  * Extreme prematurity, defined as gestational age less than 32 weeks.
  * Syndromic short stature defined by the presence of significant dysmorphic features and/OR major malformations, Laron syndrome, Prader-Willi syndrome, Russell-Silver syndrome.
  * Significant developmental delays, autism spectrum or intellectual deficit of any degree.
  * Skeletal dysplasia.
  * Magnetic resonance imaging (MRI) result confirming pituitary structural abnormalities.
  * Poor adherence to GH therapy or interruption of it for any time during the first year of therapy, as judged by the treating physician.

Where this trial is running

Columbia, Maryland and 1 other locations

• Novo Nordisk Investigational Site — Columbia, Maryland, United States (Recruiting)
• University of Sao Paulo School of Medicine — São Pauloa, Brazil (Enrolling_by_invitation)

Study contacts

• Study coordinator: Novo Nordisk

Conditions Idiopathic Short Stature