Aromatase inhibitors in girls: Anastrozole combined to the LHRH analogue leuprorelin in Girls with early or precocious puberty and a compromised growth potential
| ISRCTN | ISRCTN11469487 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11469487 |
| Secondary identifying numbers | 9804 |
- Submission date
- 13/12/2014
- Registration date
- 13/01/2015
- Last edited
- 17/04/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English Summary
Background and study aims:
The pituitary gland is a pea-sized structure in the brain that makes, amongst other things, a chemical called the growth hormone. Growth hormone deficiency occurs when this gland does not produce enough growth hormone. This deficiency can develop at any age. In children, it results in slow growth compared to children of the same age with the affected child looking smaller and younger than their peers. Treatment with aromatase inhibitors have been shown to be successful in increasing predicted adult height (PAH) in boys, but, in girls, it has only shown to be successful for those that have McCune-Albright syndrome (a genetic disorder). Luteinising hormone is another hormone produced in the pituitary gland. It stimulates the production of the sex hormones, including oestrogen. Oestrogen promotes the maturation of the skeletal bones, which leads to a slow in growth. Blocking the production of luteinising hormone using a drug called leuprorelin slows down bone maturation and therefore potentially increases the amount of time available for growth. We want to investigate whether anastrozole (a aromatase inhibitor) combined with leuprorelin for up to 2 years (or until the age of 11 years) is a safe and effective treatment for improving PAH in girls with precocious (very early) or early puberty with a compromised (less than usual) growth potential, compared to leuprorelin alone.
Who can participate?
Girls with idiopathic precocious (breast development occurring before 7.5 years) or early puberty (breast development occurring between 7.5-9 years), that have not had hormone therapy before and a compromised growth potential .
What does the study involve?
Participants are randomly allocated into one of two groups. Those in group 1 receive a combination of leuprorelin and anastrozole for 2 years or until they reach the age of 11 years. Those in group 2 are given only leuprorelin for 2 years or until they reach the age of 11 years. After completing the initial phase of treatment , girls on the combined treatment are then randomised to receive anastrozole or no treatment at all and followed up every 6 months until bone age reaches 14 years or they reach near adult height. Girls on leuprorelin only are followed up every 6 months with no relevant treatment until bone age reaches 14 years or near adult height is achieved. Follow-up includes clinical examination, hormonal and biochemical measurements, pelvic ultrasound and a bone age X-ray. DXA scans and X-rays of the lumbar spine are assessed yearly.
What are the possible benefits and risks of participating?
Parents are informed that anastrozole treatment is an off-label treatment and will be asked to sign a written informed consent. Anastrozole is safe for humans. While widely used off-label in boys, in girls it has been given mainly as a treatment for McCune-Albright syndrome. In a previous trial, 5 girls received the combined treatment. There were no side effects in any of the girls.
Where is the study run from?
1. Pediatric Endocrine Unit, Attikon University Hospital, Athens (Greece)
2. Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, Athens (Greece)
When is the study starting and how long is it expected to run for?
January 2008 to December 2017
Who is funding the study?
Investigator initiated and funded (Greece)
Who is the main contact?
Dr Dimitrios T. Papadimitriou
info@pedoendo.gr
Contact information
Scientific
58, av Kifisias
15125
Marousi
15125
Greece
| Phone | +302103638536 |
|---|---|
| info@pedoendo.gr |
Study information
| Study design | Prospective Phase IIa and IIb study, performed in two cooperating centers. |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format |
| Scientific title | The aromatase inhibitor anastrozole combined to the LHRH analogue leuprorelin vs leuprorelin alone in ameliorating predicted adult height In girls with early or precosious puberty with a compromised growth potential |
| Study acronym | GAIL (Girls treated with an Aromatase Inhibitor plus Leuprorelin) |
| Study hypothesis | Whether the combination of an aromatase inhibitor (anastrozole) with an LHRH analogue (leuprorelin) can significantly improve predicted adult height in girls with idiopathic precocious or early puberty and a compromised growth potential compared to inhibition of puberty alone. |
| Ethics approval(s) | Attikon University Hospital Ethics Committee, 2008, ref: 36/2008 13/3/08. |
| Condition | Compromised predicted adult height in girls with early or precocious puberty |
| Intervention | An initial phase IIa trial with 5 girls on the combined treatment for 1 year was performed. Girls with idiopathic precocious (<7.5yrs) or early (7.5-9yrs) puberty, all with a PAH lower than -2 or more than 1.5 SDS lower than their target height (TH) are randomized on leuprorelin 0.3 mg/kg/month plus anastrozole 1 mg/day p.o. (group-A) or on leuprorelin only (group-B) for 2 yrs or until the age of 11 yrs. After completion of this initial phase, girls on the combined treatment will be randomized to anastrozole monotherapy 1 mg/day p.o. or no treatment and followed every 6 months until bone age reaches reaches 14 years or near adult height is achieved (height velocity < 2 cm/year). The girls on leuprorelin only will be followed every 6 months without any relevant hormonal treatment until bone age reaches 14 years or near adult height is achieved. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | 1. Anastrozole 2. Leuprorelin |
| Primary outcome measure | 1. Predicted adult height calculated according to the Bayley Pinneau tables with a bone age calculated according to the atlas of Greulich and Pyle, at 6-12-18-24 months. 2. Height velocity 3. Height for bone age 4. Bone age advancement 5. BMI Participants are followed until bone age reaches 14 or near adult height is achieved. |
| Secondary outcome measures | 1. Potential hyperandrogenism (clinical or biochemical) 2. Ovarian cyst formation (pelvic ultrasound) 3. Bone mineral density (evaluated yearly by DXA) 4. Radiological evaluation of the lumbar spine (yearly) 5. Reports of peculiar behavior |
| Overall study start date | 01/01/2008 |
| Overall study end date | 31/12/2017 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Child |
| Sex | Female |
| Target number of participants | At least 40, 20 in each treatment group |
| Total final enrolment | 40 |
| Participant inclusion criteria | 1. Idiopathic precocious (breast development < 7.5 yrs) or early puberty (breast development 7.5-9 yrs) 2. Previously naïve to any hormonal therapy 3. PAH lower than -2 SDS or -1.5 SDS lower than their target height (mid parental height -6.5 cm) |
| Participant exclusion criteria | 1. Organic precocious puberty 2. Syndromic, systemic or hereditary conditions that either impair growth or associate with PP 3. Bone diseases related to short stature (i.e. hypochondroplasia) |
| Recruitment start date | 01/01/2008 |
| Recruitment end date | 31/12/2014 |
Locations
Countries of recruitment
- Greece
Study participating centres
Haidari
Athens
12462
Greece
Marousi
Athens
15125
Greece
Sponsor information
University/education
Rimini 1
Haidari
12462
Greece
| Phone | +302105832046 |
|---|---|
| pedattikon@gmail.com | |
| Website | www.attikonhospital.gr/ |
Hospital/treatment centre
Distomou 5
Athens
Marousi
Greece
| Phone | +302106862172 |
|---|---|
| info@iatriko.gr | |
| Website | http://www.iatriko.gr/ |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 30/03/2015 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Results were reported as an oral awarded poster to the 2014 ESPE meeting and were published in the supplement issue of Hormone Research |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/04/2016 | Yes | No | |
| Results article | 08/05/2020 | 08/02/2023 | Yes | No | |
| Other publications | results from the second phase of the GAIL study | 02/04/2024 | 17/04/2024 | Yes | No |
Editorial Notes
17/04/2024: Publication reference added.
08/02/2023: Publication reference and total final enrolment added.
03/01/2016: Publication reference added.
10/10/2016: Internal review
