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Minipuberty and Its Effects on Preterm Neonates

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ClinicalTrials.gov Identifier: NCT03858127
Recruitment Status : Not yet recruiting
First Posted : February 28, 2019
Last Update Posted : March 7, 2019
Sponsor:
Information provided by (Responsible Party):
NHS Greater Glasgow and Clyde

Brief Summary:

It is generally known that there are some hormonal changes during puberty, but the knowledge about the activation of the same hormonal axis in the first months of life is relatively recent and it is not completely understood.

From the first weeks of life there is a progressive increase in hormone levels and this post-natal activation is called "minipuberty". Particularly in males, testosterone and androgen levels are associated with development and maturation of the reproductive system as well as changes in the brain structure and behaviours. Recently, it has also been suggested that the increasing testosterone level during the first 6 months of life, as well as during puberty, translates into an increase of linear growth.

In preterm neonates these hormones rise higher and for longer than in full-term newborns, suggesting that its activity is evolutionarily regulated.

With this study researchers would like to investigate these changes and correlate hormone levels with linear growth and neurobehavioral development of preterm infants.


Condition or disease Intervention/treatment
Infant, Newborn Other: Collection of urine sample Other: Examination of genitalia Other: Video messaging

Detailed Description:

The activation of the hypothalamic-pituitary-gonadal axis (HPG) develops through three main moments: foetal life, first postnatal months (usually first 6 months of life) and finally during puberty. During the foetal period, there is a peak of gonadotropin secretion starting from the second trimester of gestation, and a subsequent suppression in the last weeks until birth, due to the negative feedback of placental estrogens. In male foetuses, LH levels exceed those of FSH. The foetal testis secretes testosterone and anti-müllerian hormone (AMH) from the 8th week of gestation and this is essential for masculinization. Formation of the active metabolite of testosterone, dihydrotestosterone, is required for the development of the prostate, penis and scrotum. Initial testicular development is intra-abdominal and the descent of the testes into the scrotum occurs in two phases. The first, transabdominal, phase is completed by 15 weeks of gestation. The second, inguinoscrotal, phase is usually completed by the end of the 35th week of gestation and this phase is androgen dependent. Testosterone levels are high in male foetuses between 10 and 20 weeks of gestational age, reaching adult values, and decrease thereafter towards term. In the same way LH and FSH levels decrease towards the end of gestation and are low at term in both sexes, due to the negative feedback of placental oestrogens.

A second post-natal HPG activation, also called "minipuberty", occurs at around 1 week of age, when placental hormones are cleared from the circulation. From the first weeks of life onwards there is a progressive increase in gonadotropins levels with a greater increase of FSH in females and of LH in males. During the "minipuberty" period gonadotropins levels have a peak at 3 months of life and a progressive exhaustion at around 6 months, except for FSH levels in females that can remain high even up to 3 or 4 years. Particularly in males, testosterone and androgen levels are associated with development and maturation of the reproductive system (penis and testis) as well as the androgynous cutaneous manifestations and a different neurobehavioral structure. Postnatal testosterone levels have been associated with male-type behaviour in 14-month-old infants, suggesting a role in neurobehavioral development.6 Recently, it has also been suggested how the increasing testosterone level during the first 6 months of life, as well as during puberty, translates into an increase of linear growth, regardless of the levels of growth hormone (GH) or insulin-like growth factor (IGF1).

Preterm birth does not seem to influence post-natal HPG activation, since that gonadotropin levels seem to raise up at the same time as term infants after the birth. The difference is that in preterm neonates these values last higher and longer than full-term newborns. According to the most recent longitudinal data, the post-natal activity of this axis declines at about the same in term neonates compared to premature infants with the same corrected gestational age, suggesting that the HPG activity is evolutionarily regulated. This higher increase of gonadotropin levels in premature males has been associated with a faster penile and testicular growth after birth compared to full-term boys. At last, in neonates small for gestational age (SGA) there are some evidence that post-natal FSH and testosterone levels are higher compared to infants with an adequate weight (AGA), although it is not known whether this correlates or have any influence on the catch-up growth of this subjects.

Understanding how "minipuberty" can influence linear growth, genitalia development and neurocognitive processes in preterm neonates has a significant scientific impact and could provide more information in understanding auxological and neurobehavioral developmental patterns of this population.


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Study Type : Observational
Estimated Enrollment : 20 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Preliminary Study on Activation of the Hypothalamic-pituitary-gonadal Axis in Infancy (Minipuberty) and Its Effects on Catch-up Growth and Neurocognitive Outcome in Male Preterm Neonates Born at <32 Weeks of Gestational Age
Estimated Study Start Date : March 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : August 2020

Group/Cohort Intervention/treatment
Male infants born <32 weeks gestation Other: Collection of urine sample
Collection of urine sample for measurement of LH and FSH

Other: Examination of genitalia
Examination of genitalia

Other: Video messaging
Short video of infant recorded at home by the parents




Primary Outcome Measures :
  1. Measurement of urinary luteinising hormone [ Time Frame: 18 months ]
    Urinary LH measured every week on fresh samples using electro- chemiluminescence immunoassay (ECLIA). Sample analysis will be performed by the Biochemistry Department of the Royal Hospital for Children in Glasgow using Abbott Architect i1600 instrument

  2. Measurement of urinary follicle stimulating hormone [ Time Frame: 18 months ]
    Urinary FSH measured every week on fresh samples using electro- chemiluminescence immunoassay (ECLIA). Sample analysis will be performed by the Biochemistry Department of the Royal Hospital for Children in Glasgow using Abbott Architect i1600 instrument


Secondary Outcome Measures :
  1. Measurement of weight [ Time Frame: 18 months ]
    Each baby will have a naked weekly weight as part of their routine care, using calibrated weighing scales

  2. Measurement of occipital frontal circumference [ Time Frame: 18 months ]
    Each baby will have a weekly OFC measured as part of their routine care using a measuring tape

  3. Measurement of penile growth [ Time Frame: 18 months ]
    Each baby will have a weekly penile length measured using a measuring tape

  4. Measurement of penile volume [ Time Frame: 18 months ]
    Each baby will have penile volume measured weekly using an orchidometer

  5. Video recording of fidgety movements [ Time Frame: 18 months ]
    Each baby will have a 4-5 minute video recording taken by their parents for Prechtl's Method For The Qualitative Assessment Of General Movements



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Ages Eligible for Study:   up to 72 Hours   (Child)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Male infants
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
We aim to enroll 20 neonates born under 32 weeks of gestational age at the Royal Hospital for Children in Glasgow. Neonates will be enrolled during the first 3 days of life with written informed consent signed by their parents.
Criteria

Inclusion Criteria:

  • Male preterm infants born ≤32 weeks of gestational age
  • Written informed consent provided

Exclusion Criteria:

  • Female sex assignment at birth
  • Male preterm infants born >32 weeks of gestational age
  • Male infants born at term

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03858127


Contacts
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Contact: Faisal Ahmed 07765422553 faisal.ahmed@glasgow.ac.uk
Contact: Martina Rodie 07973887549 martina.rodie@nhs.net

Sponsors and Collaborators
NHS Greater Glasgow and Clyde
Investigators
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Study Director: Paul Dearie NHS GGC R&D
  Study Documents (Full-Text)

Documents provided by NHS Greater Glasgow and Clyde:

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Responsible Party: NHS Greater Glasgow and Clyde
ClinicalTrials.gov Identifier: NCT03858127     History of Changes
Other Study ID Numbers: GN18ME668P
First Posted: February 28, 2019    Key Record Dates
Last Update Posted: March 7, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No