Condition category
Nutritional, Metabolic, Endocrine
Date applied
09/02/2018
Date assigned
12/02/2018
Last edited
12/02/2018
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

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

Trial website

Contact information

Type

Scientific

Primary contact

Dr Dimitrios Papadimitriou

ORCID ID

http://orcid.org/0000-0002-6083-3560

Contact details

58
av. Kifisias
Marousi
Athens
15125
Greece
+30 (0)2103638536
info@pedoendo.gr

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

17/2009

Study information

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®)

Acronym

REplacement of MAle mini Puberty (REMAP)

Study hypothesis

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

Athens Medical Center Scientific Board and Ethics Committee, 01/05/2009, No 17/2009

Study design

Non-randomised study

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details to request a patient information sheet

Condition

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

Phase

Phase II

Drug names

Pergoveris (rLH 75IU/FSH 150 IU)

Primary outcome measures

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 trial start date

01/01/2009

Overall trial end date

31/12/2020

Reason abandoned

Eligibility

Participant inclusion criteria

Male neonates and infants with micropenis and/or cryptorchidism with hypogonadotropic hypogonadism

Participant type

Patient

Age group

Neonate

Gender

Male

Target number of participants

10

Participant exclusion criteria

Gonadal dysgenesis, partial androgen resistance, 5-a reductase deficiency

Recruitment start date

01/06/2009

Recruitment end date

31/05/2019

Locations

Countries of recruitment

Greece

Trial participating centre

Athens Medical Center
Department of Pediatric-Adolescent Endocrinology & Diabetes 58 av. Kifisias
Marousi
15125
Greece

Sponsor information

Organisation

Athens Medical Center

Sponsor details

5-7
Distomou str
Marousi
15125
Greece
+30 (0)2106198100
info@iatriko.gr

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Other

Funder name

Investigator initiated and funded

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

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 statement
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.

Intention to publish date

01/12/2018

Participant level data

Available on request

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes