Replacement of male mini puberty in neonates and children with micropenis and/or cryptorchidism due to hypogonadotropic hypogonadism
| ISRCTN | ISRCTN13007297 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN13007297 |
| Secondary identifying numbers | 17/2009 |
- Submission date
- 09/02/2018
- Registration date
- 12/02/2018
- Last edited
- 11/06/2019
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nutritional, Metabolic, Endocrine
Plain English summary of protocol
Background and study aims
Male hypogonadotropic hypogonadism is a condition where a lack of hormones can result in micropenis and bilateral cryptorchidism (where the testes do not descend from the abdomen to the scrotum). Micropenis has been traditionally successfully treated with hormone replacement, usually with 3 monthly injections of testosterone, but bilateral cryptorchidism requires surgery - usually twice. The aim of this study is to find out whether daily injections of LH and FSH hormones (Pergoveris®) can successfully treat bilateral cryptorchidism, repair micropenis, and reinstate normal growth.
Who can participate?
Male babies/ infants with bilateral cryptorchidism and micropenis
What does the study involve?
Participants are treated for 3 months with daily injections of Pergoveris®. Parents are trained to perform the injections. Penile length, testicular volume and position, and hormone levels are monitored before, during and at the end of treatment. Ultrasound examination of the testes is performed before and after the end of treatment.
What are the possible benefits and risks of participating?
The treatment may repair micropenis and bilateral cryptorchidism. It is non-invasive, costs less than two surgical operations, is feasible to perform at home by the parents, and preserves future fertility. Based on early results, it is safe with no side effects.
Where is the study run from?
Athens Medical Center (Greece)
When is the study starting and how long is it expected to run for?
January 2009 to December 2020
Who is funding the study?
Investigator initiated and funded
Who is the main contact?
Dr Dimitrios Papadimitriou
info@pedoendo.gr
Contact information
Scientific
58, av. Kifisias
Marousi, Athens
15125
Greece
 ORCID ID |
0000-0002-6083-3560 |
|---|---|
| Phone | +30 (0)2103638536 |
| info@pedoendo.gr |
Study information
| Study design | Non-randomised study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Non randomised study |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | Treatment of neonatal micropenis and bilateral cryptorchidism due to hypogonadotropic hypogonadism (HH) with 3-month daily subcutaneous injections of the commercially available recombinant FSH plus recombinant LH preparation (Pergoveris®) |
| Study acronym | REplacement of MAle mini Puberty (REMAP) |
| Study objectives | Hormonal replacement in boys with congenital HH remains a challenge in pediatric endocrinology. Micropenis has been traditionally successfully treated, usually with 3 monthly injections of 50 mg of testosterone enanthate in the post-neonatal period or in early infancy, but when bilateral cryptorchidism coincides, surgical intervention - usually needed twice - is required. Even after a successful surgery, the hypoplastic testes with the deficient proliferation of immature Sertoli cells before and during puberty, due mainly to the lack of the male mini-puberty in the neonatal period as well as the subsequent midinfancy surge in pulsatile gonadotropin secretion, are condemned in azoospermia and the boys in infertility later in their adult life. The aim of this study is to investigate whether early postnatal daily injections of the commercially available recombinant LH plus FSH preparation (Pergoveris®) could mimic the physiological male mini puberty and successfully resolve bilateral cryptorchidism, repair micropenis, reinstate normal growth in the post neonatal period and restore the responses of the Leydig and Sertoli cells to normal. |
| Ethics approval(s) | Athens Medical Center Scientific Board and Ethics Committee, 01/05/2009, No 17/2009 |
| Health condition(s) or problem(s) studied | Hypogonadotropic hypogonadism in neonates and infants |
| Intervention | Neonates or infants all with micropenis and/or bilateral cryptorchidism with absence of neonatal male mini-puberty will be treated for 3 months with daily subcutaneous injections of Pergoveris® (recombinant LH 75 IU and FSH 150 IU), followed monthly. Parents are trained to perform the injections at home. Penile length, testicular volume and position, LH, FSH, Testosterone, AMH and Inhibine b are monitored before, during and at the completion of treatment. Ultrasound examination of the testes by a pediatric radiologist is performed before and after completion of therapy. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Pergoveris (rLH 75IU/FSH 150 IU) |
| Primary outcome measure | Measured at baseline and 1 – 2 – 3 months after initiation of therapy: 1. Stretched penile length measured with a ruler 2. Testicular volume measured with a Prader Orchidometer 3. Ultrasound measurements of the testes recorded by an experienced Pediatric Radiologist |
| Secondary outcome measures | Height velocity and body measurements recorded and analysed by Growth Analyser ver 3.1 at baseline and 1 – 2 – 3 months after initiation of therapy |
| Overall study start date | 01/01/2009 |
| Completion date | 31/12/2020 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Neonate |
| Sex | Male |
| Target number of participants | 10 |
| Total final enrolment | 10 |
| Key inclusion criteria | Male neonates and infants with micropenis and/or cryptorchidism with hypogonadotropic hypogonadism |
| Key exclusion criteria | Gonadal dysgenesis, partial androgen resistance, 5-a reductase deficiency |
| Date of first enrolment | 01/06/2009 |
| Date of final enrolment | 31/05/2019 |
Locations
Countries of recruitment
- Greece
Study participating centre
58 av. Kifisias
Marousi
15125
Greece
Sponsor information
Hospital/treatment centre
5-7, Distomou str
Marousi
15125
Greece
| Phone | +30 (0)2106198100 |
|---|---|
| info@iatriko.gr | |
"ROR" |
https://ror.org/03078rq26 |
Funders
Funder type
Other
No information available
Results and Publications
| Intention to publish date | 01/12/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | 55th Annual Meeting of the European Society of Paediatric Endocrinology, Abstract No. 1158, Title Replacement of male minipuberty. Presentation INVITED PROGRAMME SPEAKER ICE/ENDO 2014, CHICAGO, U.S., ORAL PRESENTATION LB-OR01-1: Successful treatment of neonatal micropenis and bilateral cryptorchidism due to hypogonadotropic hypogonadism (HH) with 3-month daily subcutaneous injections of the commercially available recombinant FSH plus recombinant LH preparation (Pergoveris®). Abstract presenting the followed protocol has already been published: Horm Res Paediatr 2016;86(suppl 1):1-556 https://doi.org/10.1159/000449142 page 121 Planning to publish the trial in NEJM or other major journal until 2019. |
| IPD sharing plan | All data at study completion will be available in Excel format on demand only by scientists or journal reviewers etc. Data will be hopefully but not necessarily published as supplementary material to the main publication of REMAP study. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | results | 01/07/2019 | 11/06/2019 | Yes | No |
Editorial Notes
11/06/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.
