Skip to content

Trial · Interventional

CompletedPhase 1/2Results postedRegistry data

Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency

Overview

Status
Completed
Phase
Phase 1/2
Enrollment
22 participants (actual)
Sponsor
Children's Hospital Medical Center, Cincinnati · Other
Design
Allocation not applicable · Open label (no masking)
Countries
1 country

United States

Start
1 Feb 2018
Primary completion
31 Mar 2023
Completion
31 Aug 2023
First posted
19 Sept 2017
Last update posted
30 Jul 2024
Conditions
Short Stature

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2018201920202021202220232024
  1. Ph 1/2

    Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency

    NCT03288103

    1 Feb 2018 to 31 Aug 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This is an open-label, single-arm prospective pilot study to study the effects of a single dose regimen of daily growth hormone medication (Norditropin) on pre-pubertal children with Aggrecan deficiency. The growth response will be tracked over a 12 month period. A protocol extension has been approved to continue subjects on treatment for an additional 2 years.

Interventions

  • NorditropinDrug

Arms1

  • Experimental

    Growth Hormone Treatment for Participants with ACAN Deficiency

    Pre-pubertal children with ACAN deficiency on daily growth hormone (Norditropin) regimen for a 3 year period.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Height Standard Deviation Score

    Time frame · Annually through three years of treatment

    Registry description

    Height Standard Deviation Score is the standard deviation above or below the mean the height is for age and gender. Values were obtained by plotting heights on Centers for Disease Control and Prevention growth charts. An increase in Height Standard Deviation Score correlates with increase in height. Results are reported for 10 patients treated with recombinant human growth hormone.

  2. Height Velocity After Three Years of Treatment With Recombinant Human Growth Hormone (rhGH)

    Time frame · Annually through three years of treatment

    Registry description

    A participants calculated height velocity derived from height measurements taken over a period of 36 months (baseline visit to 36 month visit). Only those in the treatment arm were treated with growth hormone and observed for response.

Secondary outcomes(2)
  1. Number of Participants With Clinical Features of ACAN Deficiency - Osteochondritis Dissecans

    Time frame · Baseline

    Registry description

    Evidence of osteochondritis dissecans on MRI (in those who could cooperate to perform such unsedated between the ages of 6 years-old and 20 years-old) or radiograph examination of affected participant's knees.

  2. Number of Participants With Clinical Features of ACAN Deficiency - Osteoarthritis

    Time frame · Baseline

    Registry description

    Evidence of early joint pathology evident (osteoarthritis) on MRI (in those who could cooperate to perform such unsedated between the ages of 6 years-old and 20 years-old) or radiograph examination of affected participant's knees, performed in those who were age appropriate and would cooperate.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMedian· Annually through three years of treatment

Height Standard Deviation Score

GroupValue (standard deviation score)
Growth Hormone Treatment for Participants With ACAN Deficiency-2.52
Primary outcomeMedian· Annually through three years of treatment

Height Velocity After Three Years of Treatment With Recombinant Human Growth Hormone (rhGH)

GroupValue (cm/year)
Growth Hormone Treatment for Participants With ACAN Deficiency5.2
Secondary and other outcome results(2)
Secondary outcomeNumber· Baseline

Number of Participants With Clinical Features of ACAN Deficiency - Osteochondritis Dissecans

GroupValue (participants)
Pediatric Phenotype Group3
Adult Phenotype Group1
Secondary outcomeNumber· Baseline

Number of Participants With Clinical Features of ACAN Deficiency - Osteoarthritis

GroupValue (participants)
Pediatric Phenotype Group0
Adult Phenotype Group8

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Treatment GroupPatients with Aggrecan (ACAN) deficiency who have been treatment with human growth hormone (rHGH) for 3 years.0 / 100 / 1010 / 10
Phenotype GroupFirst degree relatives of patients in the treatment group who also have Aggrecan (ACAN) deficiency but did not participate in the treatment trial.0 / 120 / 120 / 12

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • ResultAlexandrou E, Dauber A, Tyzinski L, Hwa V, Andrew M, Kim H, Elangovan S, Gubanich P, Taylor-Haas JA, Paterno M, Backeljauw P. Clinical phenotype and musculoskeletal characteristics of patients with aggrecan deficiency. Am J Med Genet A. 2022 Apr;188(4):1193-1203. doi: 10.1002/ajmg.a.62639. Epub 2022 Jan 9. PMID 35001504
  • ResultMuthuvel G, Dauber A, Alexandrou E, Tyzinski L, Andrew M, Hwa V, Backeljauw P. Treatment of Short Stature in Aggrecan-deficient Patients With Recombinant Human Growth Hormone: 1-Year Response. J Clin Endocrinol Metab. 2022 Apr 19;107(5):e2103-e2109. doi: 10.1210/clinem/dgab904. PMID 34922359

Eligibility

Who could join, as posted.

Sex
All
Age
from 2 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. ACAN Deficiency - Patients must be heterozygous for a mutation in the ACAN gene. A mutation will be defined as: a. A heterozygous deletion of the entire gene or of \>1 complete exons of the gene b. Any truncating mutation including frameshift, nonsense, splice site mutations within 2 bases of the exon/intron boundary, and start loss variants c. Any missense mutation which meets the following criteria: i. It is absent in the Exome Aggregation Consortium Database (exac.broadinstitute.org) ii. It is predicted to be damaging by both Polyphen2 and Sorting Intolerant From Tolerant (SIFT) iii. It segregates with the short stature phenotype in the family or is a de novo mutation d. In-frame insertions or deletions of \>1 amino acid e. In-frame insertions or deletions of 1 amino acid must meet the same criteria as missense mutations. For the prediction programs, Alanine will be substituted for the deleted amino acid. f. Note - Retrospective data does not show any correlation between the type of mutation and the severity of short stature. Therefore, all mutations meeting the above criteria will be included as a single group. 2. Age - Greater than or equal to 2 years 0 days. There is no specific upper age limit, but the onset of puberty will make the patient ineligible. 3. Pre-pubertal 1. Male subjects must have a testicular volume \<4 cc as determined on physical examination by a pediatric endocrinologist at the time of the screening visit 2. Female subjects must be Tanner 1 for breast development as determined on physical examination by a pediatric endocrinologist at the time of the screening visit 4. Bone Age - The bone age as determined by the Greulich and Pyle method must be equal to or greater than the chronological age. Bone ages will be determined at the screening visit by a single centralized radiologist. 5. Insulin-like growth factor (IGF-I) level within normal range for age and sex. 6. Ability to provide informed consent before any trial-related activities 7. Note - There is no specific height standard deviation criteria for inclusion in this study. Exclusion Criteria: 1. Prior treatment with any of the following therapies: A. Growth hormone B. Insulin-like Growth Factor (IGF-I) C. Gonadotropin releasing hormone (GnRH) analog D. Aromatase Inhibitor E. Oxandrolone 2. History of any type of malignancy 3. Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years in females and 15 years in males 4. Chronic medical condition known to affect growth including but not limited to: A. Cystic fibrosis B. Diabetes C. Inflammatory Bowel Disease D. Celiac Disease E. Asthma requiring a daily inhaled steroid dose \> 400 micrograms of inhaled budesonide per day or equivalent F. Taking daily oral glucocorticoids for any reason G. Note - attention deficit hyperactivity disorder (ADHD) treated with a stimulant and treated hypothyroidism with a normal thyroid stimulating hormone (TSH) will not exclude the subject from participating in the trial. 5. (BMI) \<5th percentile (CDC growth charts) 6. Any clinically significant abnormality on screening laboratory tests as determined by the principal investigator. 7. Known or suspected allergy to trial medication, excipients, or related products. 8. Contraindications to study medications, worded specifically as stated in the product's prescribing information. 9. The receipt of any investigational drug within 90 days prior to this trial.

PepBank is a research reference. Talk to a doctor before you use any peptide.