A Phase 1/2 interventional study of Norditropin in Short Stature, sponsored by Children's Hospital Medical Center, Cincinnati. Completed at 1 site in United States. Open to participants aged 2 Years and older. Per ClinicalTrials.gov, last updated 2024-07-30.
Sponsored by Children's Hospital Medical Center, Cincinnati · Phase 1/2, Interventional, and Treatment
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.
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.
99 studies on the registry are indexed under Dwarfism; 12 are open to participants now.
This study's enrollment of 22 is below the median of 60 across 66 interventional studies indexed under Dwarfism.
Browse Dwarfism studies →Children's Hospital Medical Center, Cincinnati is the lead sponsor of 673 studies on the registry; 130 are open to participants now.
Of its 57 completed or terminated interventional studies of FDA-regulated products, 31 (54%) have results posted.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
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.
Pre-pubertal
Exclusion Criteria:
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
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 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.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Pre-pubertal children with ACAN deficiency on daily growth hormone (Norditropin) regimen for a 3 year period.
Drug: Norditropin
Single dose of daily growth hormone regimen. Dose will be 50 micrograms/kg/day.
Also known as: somatropin
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.
Time frame: 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.
Time frame: Annually through three years of treatment
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.
Time frame: 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.
Time frame: Baseline
| Milestone | Treatment Group | Pediatric Phenotype Group | Adult Phenotype Group |
|---|---|---|---|
| Started | 10 | 2 | 10 |
| Completed | 10 | 2 | 10 |
| Not completed | 0 | 0 | 0 |
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.
| standard deviation score | Growth Hormone Treatment for Participants With ACAN Deficiency |
|---|---|
| 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) |
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.
| cm/year | Growth Hormone Treatment for Participants With ACAN Deficiency |
|---|---|
| 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) |
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.
| participants | Pediatric Phenotype Group | Adult Phenotype Group |
|---|---|---|
| Number of Participants With Clinical Features of ACAN Deficiency - Osteochondritis Dissecans | 3 | 1 |
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.
| participants | Pediatric Phenotype Group | Adult Phenotype Group |
|---|---|---|
| Number of Participants With Clinical Features of ACAN Deficiency - Osteoarthritis | 0 | 8 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Treatment Group | 0/10 (0%) | 0/10 (0%) | 10/10 (100%) |
| Phenotype Group | 0/12 (0%) | 0/12 (0%) | 0/12 (0%) |
| Event | Treatment Group | Phenotype Group |
|---|---|---|
| Knee PainMusculoskeletal and connective tissue disorders | 4/10 | 0/12 |
| HeadacheGeneral disorders | 4/10 | 0/12 |
| FeverInfections and infestations | 3/10 | 0/12 |
| Ankle PainMusculoskeletal and connective tissue disorders | 3/10 | 0/12 |
| ConjunctivitisEye disorders | 2/10 | 0/12 |
| Ear InfectionEar and labyrinth disorders | 2/10 | 0/12 |
| VomitingGeneral disorders | 2/10 | 0/12 |
| Sore ThroatEar and labyrinth disorders | 2/10 | 0/12 |
| Stomach pain/discomfortGastrointestinal disorders | 2/10 | 0/12 |
| Foot painMusculoskeletal and connective tissue disorders | 2/10 | 0/12 |
| Age, Categorical(Participants) | Treatment Group | Phenotype Only Group | Total |
|---|---|---|---|
| <=18 years | 10 | 2 | 12 |
| Between 18 and 65 years | 0 | 10 | 10 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Treatment Group | Phenotype Only Group | Total |
|---|---|---|---|
| Female | 6 | 6 | 12 |
| Male | 4 | 6 | 10 |
| Race (NIH/OMB)(Participants) | Treatment Group | Phenotype Only Group | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 1 |
| White | 9 | 11 | 20 |
| More than one race | 0 | 1 | 1 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Treatment Group | Phenotype Only Group | Total |
|---|---|---|---|
| United States | 10 | 12 | 22 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — Potential to share de-identified data with the primary Endocrinologist in charge of participant's clinical care
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Studies of the drug tested here: Human Growth Hormone
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