Condition category
Nutritional, Metabolic, Endocrine
Date applied
30/03/2020
Date assigned
02/06/2020
Last edited
02/06/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Worldwide, many children suffer from cancer or hematological disorders and this number is on the rise. However, due to advances in treatment, the survival rate of these children is continuously improving being nowadays above 80%. One of the most prevalent long-term side effects of these treatments is life-long sterility or subfertility. Because sterility affects an individual’s psychological and social wellbeing, it is relevant to develop an adequate fertility preservation strategy in order to guarantee the patient’s quality of life on the long-term. Since pre- and peripubertal boys have not yet entered puberty, they do not produce mature spermatozoa and consequently they cannot benefit from sperm banking before being exposed to gonadotoxic treatment. Currently, the only option for pre- and peripubertal boys who do not yet produce mature spermatozoa is to bank testicular tissue before gonadotoxic treatment followed by auto-transplantation at adulthood. Since 2002, more than 100 pre- and peripubertal boys banked their testicular tissue for fertility preservation purposes at the Universitair Ziekenhuis Brussel. Some of these young boys are followed-up by an endocrinologist to monitor their pubertal and endocrine development, however, this follow-up is currently far from regular and standardized. Furthermore, the impact of removing testicular tissue (biopsy) at a young age on the pubertal and endocrine development is difficult to predict. Although evidence demonstrates that immediate surgical complications of such a biopsy procedure are rare (1%), nothing is known on the possible adverse effects on the long-term. The aim of this study is first to establish a more standardized follow-up protocol for young boys diagnosed with cancer or hematological disorders and undergoing a testicular tissue biopsy procedure at a young age as a fertility preservation strategy. Secondly, we aim to investigate how a testicular tissue biopsy procedure performed at a young age may affect the pubertal and endocrine development of young boys diagnosed with cancer or hematological disorders.

Who can participate?
Pre- and peripubertal boys (<18 years) who do not yet produce mature spermatozoa, who have been diagnosed with childhood cancer or childhood hematological disorders.

What does the study involve?
All available data related to the pubertal and endocrine development will be collected from the patients’ medical records over several years and compared between patients who underwent a testicular tissue biopsy procedure and those who did not.

What are the possible benefits and risks of participating?
In the short term, former childhood cancer patients will be followed-up in a more standardized way. Participating patients will receive additional information regarding their pubertal and endocrine development and hormonal status. In case of problems, immediate action can be taken, such as starting hormonal substitution therapy. As a result, patients interested in fertility preservation will be better counselled and better informed at the start of their cancer treatment. In the long term, the study will provide better insight into whether the removal of testicular tissue (testicular biopsy) at a young age may affect the pubertal and endocrine development. This knowledge could lead to improved fertility preservation strategies which will improve the patient’s quality of life.

Where is the study run from?
1. Universitair Ziekenhuis Brussel (Belgium)
2. Vrije Universiteit Brussel (Belgium)

When is the study starting and how long is it expected to run for?
January 2018 to December 2029

Who is funding the study?
1. Research Programme of the Research Foundation - Flanders (FWO) (Belgium)
2. Kom op tegen Kanker (KOTK) (Belgium)

Who is the main contact?
Prof. Eileen Goossens (scientific), ellen.goossens@vub.be
Prof. Inge Giles (public), inge.gies@uzbrussel.be

Trial website

Contact information

Type

Scientific

Primary contact

Prof Ellen Goossens

ORCID ID

http://orcid.org/0000-0001-7601-9689

Contact details

Vrije Universiteit Brussel
Laarbeeklaan 103
Brussels
1090
Belgium
+32 24749213
ellen.goossens@vub.be

Type

Public

Additional contact

Prof Inge Gies

ORCID ID

http://orcid.org/0000-0002-8571-0858

Contact details

Universitair Ziekenhuis Brussel
Laarbeeklaan 101
Brussels
1090
Belgium
+32 24744180
inge.gies@uzbrussel.be

Additional identifiers

EudraCT number

Nil known

ClinicalTrials.gov number

Nil known

Protocol/serial number

B.U.N. 143201733195

Study information

Scientific title

Follow-up of pubertal and endocrine development in boys who stored testicular tissue for fertility preservation before high-risk gonadotoxic treatment

Acronym

Study hypothesis

Harvesting testicular tissue from pre- and peripubertal boys does not have an additional negative impact on their pubertal and endocrine development

Ethics approval

Approved 08/11/2017, Medical Ethics Committee of the Universitair Ziekenhuis Brussel (Vrije Universiteit Brussel (VUB)
Laarbeeklaan 101, 1090 Brussels, Belgium; +32 2 477 55 84; commissie.ethiek@uzbrussel.be), ref: B.U.N. 143201733195

Study design

Single-center prospective comparative observational cohort study

Primary study design

Observational

Secondary study design

Cohort study

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet.

Condition

Childhood cancer, childhood hematological disease

Intervention

The study population consists of pre- and peripubertal boys (<18 years) diagnosed at the Universitair Ziekenhuis Brussel with cancer or hematological disorders for which they need high-risk gonadotoxic treatment (with an ≥80% risk of later fertility problems).

Data on their pubertal and endocrine development (Tanner stage, testicular volume, reproductive hormones and other endocrine markers, bone age and density) will be collected at diagnosis and yearly from the end of the gonadotoxic treatment until the age of 18 years. These collected data will be compared between young boys who did and those who did not undergo a testicular tissue biopsy procedure at a young age as a fertility preservation strategy in order to identify a possible association between the biopsy procedure (which is performed to harvest testicular tissue) and the pubertal and endocrine development.

The following data will be collected from the patient’s medical records:
- The patient's medical background: the diagnosis and the patient’s age at time of diagnosis, the type of treatment received with mention of the cumulative dose (chemotherapy, radiotherapy, total body irradiation, bone marrow transplantation, type and frequency of surgery, …).
- Whether or not a testicular tissue biopsy procedure has been performed at a young age with mention of the testis portion biopsied (orchiectomy, hemi-orchiectomy or smaller portion), the site of biopsy (left, right or bilateral), the patient’s age at time of biopsy and the reason why the patient and his parents accepted or refused testicular tissue banking.

The following examinations and procedures will be performed at diagnosis and yearly until the age of 18 years (starting from the end of the gonadotoxic treatment):
- A physical examination to measure the patient’s weight, height, body mass index, blood pressure and testicular volume using a Prader orchidometer and to determine the patient’s Tanner stage (scoring of patient’s pubertal maturation).
- A scrotum ultrasound to measure the patient’s testicular volume and to investigate potential abnormalities in the testicular parenchyma.
- A morning blood sample to evaluate the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), inhibin B (INHB), anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), insulin-like growth factor 1 (IGF1), prolactin (PRL), cortisol and adrenocorticotropic hormone (ACTH) with mention of possible hormonal substitution treatment (start, duration and dose prescribed).
- An X-ray of the left hand and wrist to determine the patient’s bone age.
- An X-ray at two different locations (i.e. trabecular bone and lumbar bone) and the total body to assess the patient’s bone density.

These data will be compared between young boys who did (biopsy group) and those who did not (control group) undergo a testicular tissue biopsy procedure at a young age using the appropriate statistical tests in order to identify a possible association between the biopsy procedure and the pubertal and endocrine development.

Intervention type

Other

Phase

Drug names

Primary outcome measure

Impact of a testicular tissue biopsy procedure performed at a young age on pubertal and endocrine development using the following measures at diagnosis and yearly until the age of 18 years (starting from the end of the gonadotoxic treatment):
1. A physical examination to measure the patient’s weight, height, body mass index, blood pressure and testicular volume using a Prader orchidometer and to determine the patient’s Tanner stage (scoring of patient’s pubertal maturation).
2. A scrotum ultrasound to measure the patient’s testicular volume and to investigate potential abnormalities in the testicular parenchyma.
3. A morning blood sample to evaluate the serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), estradiol (E2), inhibin B (INHB), anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), insulin-like growth factor 1 (IGF1), prolactin (PRL), cortisol and adrenocorticotropic hormone (ACTH) with mention of possible hormonal substitution treatment (start, duration and dose prescribed).
4. An X-ray of the left hand and wrist to determine the patient’s bone age.
5. An X-ray at two different locations (i.e. trabecular bone and lumbar bone) and the total body to assess the patient’s bone density.

Secondary outcome measures

1. The patient's medical background: the diagnosis and the patient’s age at time of diagnosis, the type of treatment received with mention of the cumulative dose (chemotherapy, radiotherapy, total body irradiation, bone marrow transplantation, type and frequency of surgery, …)
2. Whether or not a testicular tissue biopsy procedure has been performed at a young age with mention of the testis portion biopsied (orchiectomy, hemi-orchiectomy or smaller portion), the site of biopsy (left, right or bilateral), the patient’s age at time of biopsy and the reason why the patient and his parents accepted or refused testicular tissue banking

Overall trial start date

01/01/2016

Overall trial end date

31/12/2030

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Pre- and peripubertal boys (<18 years) who do not yet produce mature spermatozoa
2. Diagnosis of childhood cancer or childhood hematological disorders (<18 years) at the Universitair Ziekenhuis Brussel
3. High-risk gonadotoxic treatment (with an ≥80% risk of later fertility problems)
4. Did or did not undergo a testicular tissue biopsy procedure at a young age as a fertility preservation strategy

Participant type

Patient

Age group

Child

Gender

Male

Target number of participants

100

Participant exclusion criteria

1. Diagnosis of testicular cancer

Recruitment start date

01/01/2018

Recruitment end date

31/12/2029

Locations

Countries of recruitment

Belgium

Trial participating centre

Universitair Ziekenhuis Brussel
Laarbeeklaan 101
Brussels
1090
Belgium

Trial participating centre

Vrije Universiteit Brussel
Laarbeeklaan 103
Brussels
1090
Belgium

Sponsor information

Organisation

Universitair Ziekenhuis Brussel

Sponsor details

Laarbeeklaan 101
Brussels
1090
Belgium
+32 24774111
info@uzbrussel.be

Sponsor type

Hospital/treatment centre

Website

https://www.uzbrussel.be/

Organisation

Vrije Universiteit Brussel

Sponsor details

Laarbeeklaan 103
Brussels
1090
Belgium
+32 26292010
info@vub.ac.be

Sponsor type

University/education

Website

https://www.vub.be/

Funders

Funder type

Government

Funder name

Research Programme of the Research Foundation - Flanders (FWO)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Kom op tegen Kanker (KOTK)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The study results will be disseminated with Belgium colleagues and other international scientists through presentations at scientific meetings and peer-reviewed publications in scientific journals.
General practitioners will be informed through journals of medicine.
The press service of the Universitair Ziekenhuis Brussel will encourage publication of important results in national papers in layman’s terms for the public.
Patients will be informed through the Centre for Reproductive Medicine (CRG) website (http://www.brusselsivf.be/) and the website of the Biology of the Testis (BITE) research group of the Vrije Universiteit Brussel (https://bite.research.vub.be/).

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date.

Intention to publish date

01/01/2031

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

02/06/2020: Uploaded protocol (not peer reviewed) as an additional file. 14/04/2020: Trial’s existence confirmed by Medical Ethics Committee of the Universitair Ziekenhuis Brussel