Idiopathic Short StaturePhase 3ThrasherAINCT01248416
Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
A Phase 3 study testing Aromatase Inhibitor, Growth Hormone and Aromatase Inhibitor and Growth Hormone in people with Idiopathic Short Stature, run by Nemours Children's Clinic at 4 sites in 2 countries.
Trial summary
When treating very short children in puberty we are time-limited, as sex hormones cause the growth plates to fuse and growth to end. Growth Hormone (GH), plus drugs that stop puberty, increase height potential, but leave children sexually infantile at a critical time in development. Read more about this study
- Who is it for?
- Ages 12 to 18 years, men only
- Conditions the study is for
- Idiopathic Short Stature
- What is being tested?
- Aromatase Inhibitor, Growth Hormone and Aromatase Inhibitor and Growth Hormone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 76 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Nov 2010to Sep 2016
- Phase
- Phase 3
- 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 12 to 18 years
- Men only
- No healthy volunteers
- Child, Adult
Who may be able to join
- Males: Ages: 12 - less than 18 years.
- Bone age less than 14 ½ years at study initiation.
- Presence of puberty.
- Idiopathic short stature will be defined as a short child equal or less than -2SD for height, with normal GH responses to stimuli (> or = 5ng/ml to at least 2 secretagogues) or a normal IGF-I and BP-3, normal body proportions and no other identifiable growth pathology.
- Accurate growth data for at least 6 months at baseline is available.
Who cannot join
- Chronic illnesses.
- Chronic use of glucocorticosteroids.
- Previous use of hormonal treatment with AIs, sex steroids or GH in the preceding 6 months.
- Birth weight small for gestational age (SGA).
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United States3 sites
Nemours Children's Clinic
Jacksonville, Florida, 32207
Nemours Children's Clinic
Orlando, Florida, 32801
Nemours Children's Clinic- Jefferson
Philadelphia, Pennsylvania, 19107
About this study
Official title: A Randomized Controlled Trial Of The Use Of Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
When treating very short children in puberty we are time-limited, as sex hormones cause the growth plates to fuse and growth to end. Growth Hormone (GH), plus drugs that stop puberty, increase height potential, but leave children sexually infantile at a critical time in development. Human and animal data show that estrogen, in females and males, is a principal regulator of the fusion of the growth plate in puberty. Using aromatase inhibitors (AIs), which block testosterone to estrogen conversion, in boys with different growth disorders, we have shown that AIs may have beneficial effects enhancing height potential in growth-retarded males, without affecting their puberty. However, no direct comparison of the effect of AIs alone vs. conventional GH treatment has been done to date. This study will assess the effect of AIs alone, GH alone and combination treatment in enhancing height potential in adolescent boys with idiopathic short stature.
- Conditions
- Idiopathic Short Stature
- Being tested
- Aromatase Inhibitor, Growth Hormone, Aromatase Inhibitor and Growth Hormone
- Keywords
- Aromatase, Growth, Letrozole, Anastrozole, GH, Children, Puberty
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aromatase InhibitorDrug
Also called Arimidex (Anastrozole), Femara (Letrozole)
Growth HormoneDrug
Also called Nutropin (Somatropin), Genotropin (Somatropin)
Aromatase Inhibitor and Growth HormoneDrug
Also called Arimidex (Anastrozole), Femara (Letrozole), Nutropin (Somatropin), Genotropin (Somatropin)
| Study group | Role | What they receive |
|---|---|---|
| Aromatase Inhibitor | Active comparator | Anastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years Receives: Drug: Aromatase Inhibitor |
| Growth Hormone | Active comparator | Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Receives: Drug: Growth Hormone |
| Aromatase Inhibitor and Growth Hormone | Active comparator | Anastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years Receives: Drug: Aromatase Inhibitor; Drug: Growth Hormone; Drug: Aromatase Inhibitor and Growth Hormone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Height
Differences in height gains
Measured: 0 to 24 months
Change in Predicted Height
Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years)
Measured: 0 to 24 months
Secondary outcomes (7)
Change in Bone Density z Score Adjusted for Height
Measured: 0 to 24 months
Change in Lean Body Mass
Measured: 0 to 24 months
Change in Body Mass Index
Measured: 0 to 24 months
Change in IGF-I Concentrations
Measured: 0 to 24 months
Change in Testosterone
Measured: 0 to 24 months
Change in Estradiol
Those taking AI alone or AI/GH combined were grouped by type, either anastrozole or letrozole.
Measured: 0 to 24 months
Change in Estrone
Measured: 0 to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2010 (estimated)
- Study startNov 2010
- Primary completionSep 2016
- Study completionSep 2016
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 (1)Papers the sponsor has linked to this study.
- Other trials for Idiopathic Short StatureStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 76 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Thrasher Research Fund, Genentech, Inc., Novartis, AstraZeneca, Pfizer
- Responsible party
- Principal investigator, Nelly Mauras, Nemours Children's Clinic
- Investigators
- Nelly Mauras, MD, Principal investigator, Nemours Children's Clinic Jacksonville
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01248416
- Sponsor's protocol ID
- 180984
- Acronym
- ThrasherAI
- Status last verified
- Jul 2018
- First submitted
- 2 Nov 2010
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mauras N, Ross JL, Gagliardi P, Yu YM, Hossain J, Permuy J, Damaso L, Merinbaum D, Singh RJ, Gaete X, Mericq V. Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature. J Clin Endocrinol Metab. 2016 Dec;101(12):4984-4993. doi: 10.1210/jc.2016-2891. Epub 2016 Oct 6.
PubMed 27710241
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Of The Use Of Aromatase Inhibitors, Alone And In Combination With Growth Hormone In Adolescent Boys With Idiopathic Short Stature
- ClinicalTrials.gov ID
- NCT01248416
- Acronym / sponsor ID
- ThrasherAI / 180984
- Conditions
- Idiopathic Short Stature
- Keywords
- Aromatase, Growth, Letrozole, Anastrozole, GH, Children, Puberty
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 76 participants (actual)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Thrasher Research Fund, Genentech, Inc., Novartis, AstraZeneca, Pfizer
- Study start
- Nov 2010
- Primary completion
- Sep 2016 (actual)
- Study completion
- Sep 2016 (actual)
- First posted
- 25 Nov 2010 (estimated)
- Results
- Posted 7 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
When treating very short children in puberty we are time-limited, as sex hormones cause the growth plates to fuse and growth to end. Growth Hormone (GH), plus drugs that stop puberty, increase height potential, but leave children sexually infantile at a critical time in development. Human and animal data show that estrogen, in females and males, is a principal regulator of the fusion of the growth plate in puberty. Using aromatase inhibitors (AIs), which block testosterone to estrogen conversion, in boys with different growth disorders, we have shown that AIs may have beneficial effects enhancing height potential in growth-retarded males, without affecting their puberty. However, no direct comparison of the effect of AIs alone vs. conventional GH treatment has been done to date. This study will assess the effect of AIs alone, GH alone and combination treatment in enhancing height potential in adolescent boys with idiopathic short stature.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Aromatase Inhibitor | Active comparator | Drug: Aromatase InhibitorAnastrozole 1mg or Letrozole 2.5mg daily orally for 2 to 3 years |
| Growth Hormone | Active comparator | Drug: Growth HormoneSomatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years |
| Aromatase Inhibitor and Growth Hormone | Active comparator | Drug: Aromatase Inhibitor, Drug: Growth Hormone, Drug: Aromatase Inhibitor and Growth HormoneAnastrozole 1mg or Letrozole 2.5mg orally daily for 2 to 3 years and Somatropin 0.3mg/kg/week divided daily subcutaneously for 2 to 3 years |
Who may qualify
- Ages
- 12 to 18 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Males: Ages: 12 - less than 18 years.
- Bone age less than 14 ½ years at study initiation.
- Presence of puberty.
- Idiopathic short stature will be defined as a short child equal or less than -2SD for height, with normal GH responses to stimuli (> or = 5ng/ml to at least 2 secretagogues) or a normal IGF-I and BP-3, normal body proportions and no other identifiable growth pathology.
- Accurate growth data for at least 6 months at baseline is available.
Key exclusion criteria (4 listed)
- Chronic illnesses.
- Chronic use of glucocorticosteroids.
- Previous use of hormonal treatment with AIs, sex steroids or GH in the preceding 6 months.
- Birth weight small for gestational age (SGA).
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 |
|---|---|---|
| Aromatase InhibitorAlso: Arimidex (Anastrozole), Femara (Letrozole) | Drug | Aromatase Inhibitor, Aromatase Inhibitor and Growth Hormone |
| Growth HormoneAlso: Nutropin (Somatropin), Genotropin (Somatropin) | Drug | Aromatase Inhibitor and Growth Hormone, Growth Hormone |
| Aromatase Inhibitor and Growth HormoneAlso: Arimidex (Anastrozole), Femara (Letrozole), Nutropin (Somatropin), Genotropin (Somatropin) | Drug | Aromatase Inhibitor and Growth Hormone |
Primary outcome
Change in Height
Time frame: 0 to 24 months
Differences in height gains
Change in Predicted Height
Time frame: 0 to 24 months
Primary efficacy end point: change in predicted height (cm) from baseline at 24 months based on change in bone age (years)
7 secondary outcomes
Change in Bone Density z Score Adjusted for Height
Time frame: 0 to 24 months
Change in Lean Body Mass
Time frame: 0 to 24 months
Change in Body Mass Index
Time frame: 0 to 24 months
Change in IGF-I Concentrations
Time frame: 0 to 24 months
Change in Testosterone
Time frame: 0 to 24 months
Change in Estradiol
Time frame: 0 to 24 months
Change in Estrone
Time frame: 0 to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27710241Mauras N, Ross JL, Gagliardi P, Yu YM, Hossain J, Permuy J, Damaso L, Merinbaum D, Singh RJ, Gaete X, Mericq V. Randomized Trial of Aromatase Inhibitors, Growth Hormone, or Combination in Pubertal Boys with Idiopathic, Short Stature. J Clin Endocrinol Metab. 2016 Dec;101(12):4984-4993. doi: 10.1210/jc.2016-2891. Epub 2016 Oct 6.
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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.
Nelly Mauras, MD principal investigator
Nemours Children's Clinic Jacksonville
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Aromatase Inhibitor, Growth Hormone and Aromatase Inhibitor and Growth Hormone in people with Idiopathic Short Stature, run by Nemours Children's Clinic at 4 sites in 2 countries.
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 5 inclusion and 4 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 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States, Chile. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 7 Jun 2018). 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?
Change in Height (time frame: 0 to 24 months). 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 NCT01248416, which also lists 1 linked publication.
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 7 Aug 2018.