Short StaturePhase 1/2NCT03288103

Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency

A Phase 1/2 study testing Norditropin in people with Short Stature, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 2 years and older
Conditions the study is for: Short Stature
What is being tested?: Norditropin
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 22 participants
Where: 1 siteUnited States
Study dates: 1 Feb 2018to 31 Aug 2023
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 2 years and older
All sexes
No healthy volunteers
Child, Adult, Older adult

Who may be able to join

ACAN Deficiency - Patients must be heterozygous for a mutation in the ACAN gene. A mutation will be defined as:
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.
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.
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.
Pre-pubertal
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

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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
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.
Insulin-like growth factor (IGF-I) level within normal range for age and sex.
Ability to provide informed consent before any trial-related activities
Note - There is no specific height standard deviation criteria for inclusion in this study.

Who cannot join

Prior treatment with any of the following therapies:
Growth hormone B. Insulin-like Growth Factor (IGF-I) C. Gonadotropin releasing hormone (GnRH) analog D. Aromatase Inhibitor E. Oxandrolone
History of any type of malignancy
Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years in females and 15 years in males
Chronic medical condition known to affect growth including but not limited to:
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.

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(BMI) <5th percentile (CDC growth charts)
Any clinically significant abnormality on screening laboratory tests as determined by the principal investigator.
Known or suspected allergy to trial medication, excipients, or related products.
Contraindications to study medications, worded specifically as stated in the product's prescribing information.
The receipt of any investigational drug within 90 days prior to this trial.

Trial locations and contacts

1 site in 1 country.

United States1 site

Cincinnati Childrens Hospital Medical Center
Cincinnati, Ohio, 45229

Other trials in United States

About this study

Official title: Clinical Characterization and Trial of Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency

Read the detailed description

This is a single center study. All participants will be recruited from the USA. The study intends to recruit pre-pubertal children for inclusion in the 1 year growth hormone treatment trial. The study also plans to collect the following detailed phenotypic data at the first study visit: height, weight, musculoskeletal evaluation, photographs, radiographs (knees, left hand), MRI of the knees. The participants will be required to return to Cincinnati Childrens Hospital Medical Center (CCHMC) for 3 study visits over the 12 month period. At the follow up visits participants will receive a routine physical/pubertal exam, joint exam, have vitals sign checked, height/weight taken, and labs drawn. A funduscopic exam will be performed to look for signs of intracranial pressure. Study participants are also required to complete phone check ins at scheduled intervals, and a locally drawn blood sample to check insulin-like growth factor (IGF1) levels approximately 3 months after treatment start date. Concomitant medications, adverse events will be recorded and updated at all study visits and phone check ins. Medication will be resupplied and shipped to the participant as needed at every point of follow up contact. If the subjects grow well enough in the first 12 months per study protocol, they are eligible to continue treatment through the study for an additional 2 years. They will continue to come to CCHMC every 6 months for follow up study visits. Study procedures will remain the same as the initial 1 year trial with the following additions: (1) local labs may need to be obtained for dose adjustment purposes, (2) repeat knee MRI may be completed for participants that are found to have early signs of joint disease on their baseline knee MRI scan.

The study will enroll interested and affected relatives of the participant in the joint phenotyping protocol as well. These participants will come to CCHMC only one time to complete the phenotyping visit. This is not an outcome of the study but the information gathered from the imaging will provide insight into the effects of ACAN mutation on the joint cartilage.

Conditions: Short Stature
Being tested: Norditropin
Medical subject headings: Dwarfism

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

NorditropinDrug
Also called somatropin
Single dose of daily growth hormone regimen. Dose will be 50 micrograms/kg/day.

Study groups in NCT03288103
Study group	Role	What they receive
Growth Hormone Treatment for Participants with ACAN Deficiency	Experimental	Pre-pubertal children with ACAN deficiency on daily growth hormone (Norditropin) regimen for a 3 year period. Receives: Drug: Norditropin

What is being measured

The primary outcome is the main question the study is designed to answer.

Height Standard Deviation Score
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.
Measured: Annually through three years of treatment
Height Velocity After Three Years of Treatment With Recombinant Human Growth Hormone (rhGH)
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.
Measured: Annually through three years of treatment

Secondary outcomes (2)

Number of Participants With Clinical Features of ACAN Deficiency - Osteochondritis Dissecans
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.
Measured: Baseline
Number of Participants With Clinical Features of ACAN Deficiency - Osteoarthritis
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.
Measured: Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Feb 201831 Aug 2023

First posted19 Sep 2017
Study start1 Feb 2018
Primary completion31 Mar 2023
Study completion31 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Short StatureStudies of the same condition, open and under way.
More trials run by Children's Hospital Medical Center, CincinnatiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 22 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03288103
Sponsor's protocol ID: 2017-1956
Status last verified: Jul 2024
First submitted: 18 Sep 2017
Last updated: 30 Jul 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No: Potential to share de-identified data with the primary Endocrinologist in charge of participant's clinical care

Publications

Alexandrou 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.
PubMed 35001504
Muthuvel 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.
PubMed 34922359

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
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A Clinical Study of Long-Term Administration of Inpegsomatropin Injection in Participants With Idiopathic Short Stature Who Have Completed Phase Ⅲ Clinical Trials
Idiopathic Short Stature
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All Short Stature trials

Study at a glance

From the registry record, last updated by the sponsor on 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Clinical Characterization and Trial of Growth Hormone Treatment in Patients With Aggrecan (ACAN) Deficiency
ClinicalTrials.gov ID: NCT03288103
Acronym / sponsor ID: 2017-1956
Conditions: Short Stature
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 22 participants (actual)
Lead sponsor: Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
Study start: 1 Feb 2018 (actual)
Primary completion: 31 Mar 2023 (actual)
Study completion: 31 Aug 2023 (actual)
First posted: 19 Sep 2017 (actual)
Results: Posted 30 Jul 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Growth Hormone Treatment for Participants with ACAN Deficiency	Experimental	Drug: NorditropinPre-pubertal children with ACAN deficiency on daily growth hormone (Norditropin) regimen for a 3 year period.

Who may qualify

Ages: 2 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult, Older adult

Key inclusion criteria (11 listed)

ACAN Deficiency - Patients must be heterozygous for a mutation in the ACAN gene. A mutation will be defined as:
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.
Pre-pubertal
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.
Insulin-like growth factor (IGF-I) level within normal range for age and sex.

Key exclusion criteria (11 listed)

Prior treatment with any of the following therapies:
History of any type of malignancy
Growth plate fusion - Defined as a bone age via the Greulich and Pyle method of 13 years in females and 15 years in males
Chronic medical condition known to affect growth including but not limited to:
(BMI) <5th percentile (CDC growth charts)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
NorditropinAlso: somatropinSingle dose of daily growth hormone regimen. Dose will be 50 micrograms/kg/day.	Drug	Growth Hormone Treatment for Participants with ACAN Deficiency

Primary outcome

Height Standard Deviation Score
Time frame: Annually through three years of treatment
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.
Height Velocity After Three Years of Treatment With Recombinant Human Growth Hormone (rhGH)
Time frame: Annually through three years of treatment
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.

2 secondary outcomes

Number of Participants With Clinical Features of ACAN Deficiency - Osteochondritis Dissecans
Time frame: Baseline
Number of Participants With Clinical Features of ACAN Deficiency - Osteoarthritis
Time frame: Baseline

Results and safety

Results posted to the registry on 30 Jul 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Treatment Group	10	10
Pediatric Phenotype Group	2	2
Adult Phenotype Group	10	10

Primary outcome: Height Standard Deviation Score

Time frame: Annually through three years of treatment. Median (Full Range). Unit: standard deviation score

Measure	Growth Hormone Treatment for Participants With ACAN Deficiency n = 10
Baseline	-2.52 (-4.27 to -1.07)
Year 1	-1.57 (-3.89 to -0.46)
Year 2	-1.19 (-3.55 to -0.08)
Year 3	-1.09 (-3.45 to -0.02)

Population analysed: 10 pre-pubertal children with Aggrecan deficiency

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

Time frame: Annually through three years of treatment. Median (Full Range). Unit: cm/year

Measure	Growth Hormone Treatment for Participants With ACAN Deficiency n = 10
Baseline	5.2 (3.8 to 7.1)
Year 1	8.3 (7.3 to 11.2)
Year 2	7.7 (5.9 to 8.8)
Year 3	6.8 (4.9 to 7.2)

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected for treatment group participants from the time of enrollment until 3 months post treatment discontinuation. Adverse event data for phenotype participants was collected from time of enrollment until one week after the completion of their one-time study visit.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment Group	0 of 10 (0%)	10 of 10 (100%)	0 of 10
Phenotype Group	0 of 12 (0%)	0 of 12 (0%)	0 of 12

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 35001504Alexandrou 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.
Results publication: PubMed 34922359Muthuvel 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.
Individual participant dataSharing planned: No. Potential to share de-identified data with the primary Endocrinologist in charge of participant's clinical care

Related trials for Short Stature

RecruitingPhase 3
Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
Turner Syndrome, Short Stature Homeobox Gene Mutation
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
RecruitingObservational study
Primordial Dwarfism Registry
MOPDII, Meier-Gorlin Syndrome
Recruiting
A Clinical Study of Long-Term Administration of Inpegsomatropin Injection in Participants With Idiopathic Short Stature Who Have Completed Phase Ⅲ Clinical Trials
Idiopathic Short Stature
RecruitingObservational study
Understanding the Subnormal Rescue ofNeurological Development in Congenital Hypothyroidism (2022E5SZEM)
Congenital Hypothyroidism, Neurodevelopmental Disorders

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Philippe Backeljauw, MD principal investigator

Cincinnati Childrens Hospital Medical Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Norditropin in people with Short Stature, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 30 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Height Standard Deviation Score (time frame: Annually through three years of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03288103, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jul 2024.