Precocious PubertyNCT01944475
Follow-up of Girls With Premature Thelarche and Precocious Puberty
An observational study of Precocious Puberty and Excess; Development, Breast, run by University of Aarhus at 2 sites in Denmark.
Trial summary
Precocious puberty - the onset of signs of puberty before 8 years of age in girls - is be physically and emotionally devastating for kids and is sometimes caused by an underlying and medical condition. One sign of precocious puberty in small girls is breast development (thelarche). Read more about this study
- Who is it for?
- Ages Up to 8 years, women only
- Conditions the study is for
- Precocious Puberty, Excess; Development, Breast
- How many people
- 50 participants
- Where
- 2 sitesDenmark
- Study dates
- Sep 2013to Sep 2014
- How long will I take part?
- 1 Day
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 8 years
- Women only
- No healthy volunteers
- Child
Study population: 0-6 year old girls diagnosed with premature thelarche or precocious puberty from 1998 to today at the Children's Section A, AUH, Skejby. Girls who are 8 years old or under at baseline (1st of september) will be contacted and asked to participate in a clinical and paraclinical re-examination.
Who may be able to join
- Clinical diagnosis of precocious puberty or premature thelarche
- 0-6 year old girls at time of diagnosis for the medical record review
- 0-8 year old girls at baseline for the re-examination
Who cannot join
- -
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Børneafdelingen A, AUH, Skejby
Aarhus N, 8200
Niels H. Birkebæk, Dr.med, PhD, +45 50860090, nielbirk@rm.dk
Mia E. Sømod, Stud.med, 45 60199810, mia.elbek.somod@studmed.au.dk
Børneafdelingen A, AUH, Skejby
Aarhus N, 8200
Niels H. Birkebæk, Dr.med, PhD, +4550860090, nielbirk@rm.dk
Mia E. Sømod, Stud.med, +4560199810, mia.elbek.somod@studmed.au.dk
About this study
Official title: Follow-up of Girls With Premature Thelarche and Precocious Puberty: a Clinical and Paraclinical Study of Girls With Thelarche and Healthy Controls
Precocious puberty - the onset of signs of puberty before 8 years of age in girls - is be physically and emotionally devastating for kids and is sometimes caused by an underlying and medical condition. One sign of precocious puberty in small girls is breast development (thelarche). This can persist without other physical changes of puberty, it may continue into precocious puberty, or it may disappear. This project will improve the diagnostics of precocious puberty in girls and improve our ability to identify which girls with thelarche, who will develop precocious puberty and need medical treatment.
Read the detailed description
The purpose of the study is
- To conduct an epidemiological study in which characteristics of 0-6 year-old girls with either premature thelarche or precocious puberty are described (as specified below)
- To conduct a clinical and para-clinical re-examination of the before-mentioned (1))0-6 year-old girls
- To compare the clinical and paraclinical parameters in point 1) mentioned 0-6 year-old girls with a control group of children at the same age, whiteout thelarche and precocious puberty. (Local Ethics Committee has approved the study of the control group, case number 1-10-72-631-12.)
The study includes a chart review of registered 0-6 year-old girls diagnosed with premature thelarche or precocious puberty from 1998 and until today at Dept. of Pediatrics A, AUH Skejby. The cohort has not earlier been examined and the number of girls in the cohort is estimated from our clinical experience with this patient group to be about 50 in total. The following characteristics from the patients records will be registered in a database:
Age at diagnosis, anthropometry (height and weight), Tanner stage - breast, Tanner stage - pubic hair, GnRH test (LH and FSH response), thyroid parameters, estrogen, prolactin, 17OHP, androstenedione, dihydroepiandrosteron (DHEA), testosterone, inhibin B, SHBG, AFP, kisspeptin, human chorionic gonadotropin (HCG), bone age, MRI of the cerebrum, US of internal genitalia, and exposures to environmental chemicals known to affect secondary sex characteristics.
The database will be developed in the program Access. The results will be reported as mean and standard deviation and minimum and maximum values for each age group by Tanner stage, if the data are normally distributed. Non-normally distributed data will be given as median and confidence intervals as well as minimum and maximum values for each Tanner stage. Data for previously studied children with suspected precocious puberty, will be reported in the same way. Statistical comparison between the groups will be made with u-paired t-test or equivalent non-parametric test, if the data is not normally distributed.
The Data Unit at Aarhus University Hospital, Skejby, identifies 0-6 year-old girls with diagnoses premature thelarche or precocious puberty in 1998 and onwards. Girls below 8 years of age at baseline of the project (1st of September 2013) will be contacted and requested to participate in a re-examination.
The follow-up is a clinical and paraclinical re-examination, where the following parameters are measured: anthropometry (height and weight), skinfold thickness, Tanner stage, bone age, GnRH test, p-estrogen, p-testosterone , p-SHBG, p- androstenedione, p-dihydroandrostendion, p-inhibin B, p-thyroid parameters, ultrasound examination of the genitalia interna and a blood sample for studies of polymorphism in the estrogen receptor gene and aromatase enzyme gene.
If the girls are unable or unwilling to attend the reexamination, they are requested to fill out a questionnaire instead as follows:
- name, social security number, date of completion the questionnaire
- current height, current weight, birth weight, origin
- date of onset of puberty if started, current pubertal development, menarche
- diseases/admissions
Regarding the mother:
- age at menarche, medicine during pregnancy/breastfeeding, diet during pregnancy/breastfeeding, use of cosmetics /cream/shampoo during pregnancy,
Regarding the family:
- others with early breast development/early puberty
The project is conducted at Dept. of Pediatrics A, Aarhus University Hospital, Skejby, Skejbygårdsvej 100, 8200 Aarhus N. The other pediatric wards in the Region of Midtjylland (located in Randers, Viborg and Herning) will be included in the project if they prefer to participate.
- Conditions
- Precocious Puberty, Excess; Development, Breast
- Keywords
- Precocious puberty, Premature thelarche, Tanner-stage, GnRH-test
- Medical subject headings
- Puberty, Precocious
What is being measured
The primary outcome is the main question the study is designed to answer.
Tanner stage (breast and pubic hair)
Measured: Up till age 21.0 years
Secondary outcomes (6)
weight
Measured: up till age 21.0 years
height
Measured: Up till age 21.0 years
Bone age
Measured: Up till age 21.0 years
LH-peak after GnRH-test
Measured: Up till age 21.0 years
Hormones (estrogen, prolactin, 17OHP, androstrendion, DHEA, testosterone, inhibin B, SHBG, AFP, kisspeptin, HCG, thyroid hormones)
Measured: Up till age 21.0 years
Ultrasound of the internal genitalia
Measured: Up till age 21.0 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionSep 2014 (estimated)
- Study completionSep 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Precocious PubertyStudies of the same condition, open and under way.
- More trials run by University of AarhusThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Enrolment
- 50 participants (estimated)
- Target duration
- 1 Day
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Collaborators
- Aarhus University Hospital Skejby
- Responsible party
- Principal investigator, Mia Elbek Sømod, University of Aarhus
- Investigators
- Niels H. Birkebæk, MD PhD, Principal investigator, Børneafdeling A, AUH, SkejbyEsben T. Vestergaard, MD, PhD, Principal investigator, Børneafdeling A, AUH, SkejbyKurt Kristensen, MD, PhD, Principal investigator, Børneafdeling A, AUH, SkejbyMia E. Sømod, Stud.med, Principal investigator, Børneafdeligen A, AUH, Skejby
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01944475
- Sponsor's protocol ID
- 1-10-72-186-13
- Status last verified
- Sep 2013
- First submitted
- 5 Sep 2013
- Last updated
- 17 Sep 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Carel JC, Leger J. Clinical practice. Precocious puberty. N Engl J Med. 2008 May 29;358(22):2366-77. doi: 10.1056/NEJMcp0800459. No abstract available.
PubMed 18509122Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update. 2004 Mar-Apr;10(2):135-47. doi: 10.1093/humupd/dmh012.
PubMed 15073143Tremblay L, Frigon JY. Precocious puberty in adolescent girls: a biomarker of later psychosocial adjustment problems. Child Psychiatry Hum Dev. 2005 Fall;36(1):73-94. doi: 10.1007/s10578-004-3489-2.
PubMed 16049645Michaud PA, Suris JC, Deppen A. Gender-related psychological and behavioural correlates of pubertal timing in a national sample of Swiss adolescents. Mol Cell Endocrinol. 2006 Jul 25;254-255:172-8. doi: 10.1016/j.mce.2006.04.037. Epub 2006 Jun 27.
PubMed 16806671Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997 Apr;99(4):505-12. doi: 10.1542/peds.99.4.505.
PubMed 9093289Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics. 2005 Dec;116(6):1323-8. doi: 10.1542/peds.2005-0012.
PubMed 16322154Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab. 2008 Dec;21(12):1113-8. doi: 10.1515/jpem.2008.21.12.1113.
PubMed 19189683Curfman AL, Reljanovic SM, McNelis KM, Dong TT, Lewis SA, Jackson LW, Cromer BA. Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol. 2011 Dec;24(6):338-41. doi: 10.1016/j.jpag.2011.01.003.
PubMed 22099730Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr. 2012 Feb;101(2):e71-5. doi: 10.1111/j.1651-2227.2011.02444.x. Epub 2011 Sep 23.
PubMed 21854448de Vries L, Guz-Mark A, Lazar L, Reches A, Phillip M. Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr. 2010 Mar;156(3):466-71. doi: 10.1016/j.jpeds.2009.09.071. Epub 2009 Nov 14.
PubMed 19914634
Study at a glance
From the registry record, last updated by the sponsor on 17 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Follow-up of Girls With Premature Thelarche and Precocious Puberty: a Clinical and Paraclinical Study of Girls With Thelarche and Healthy Controls
- ClinicalTrials.gov ID
- NCT01944475
- Acronym / sponsor ID
- 1-10-72-186-13
- Conditions
- Precocious Puberty, Excess; Development, Breast
- Keywords
- Precocious puberty, Premature thelarche, Tanner-stage, GnRH-test
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Collaborators
- Aarhus University Hospital Skejby
- Study start
- Sep 2013
- Primary completion
- Sep 2014 (estimated)
- Study completion
- Sep 2014 (estimated)
- First posted
- 17 Sep 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Precocious puberty - the onset of signs of puberty before 8 years of age in girls - is be physically and emotionally devastating for kids and is sometimes caused by an underlying and medical condition. One sign of precocious puberty in small girls is breast development (thelarche). This can persist without other physical changes of puberty, it may continue into precocious puberty, or it may disappear. This project will improve the diagnostics of precocious puberty in girls and improve our ability to identify which girls with thelarche, who will develop precocious puberty and need medical treatment.
Detailed description
The purpose of the study is
- To conduct an epidemiological study in which characteristics of 0-6 year-old girls with either premature thelarche or precocious puberty are described (as specified below)
- To conduct a clinical and para-clinical re-examination of the before-mentioned (1))0-6 year-old girls
- To compare the clinical and paraclinical parameters in point 1) mentioned 0-6 year-old girls with a control group of children at the same age, whiteout thelarche and precocious puberty. (Local Ethics Committee has approved the study of the control group, case number 1-10-72-631-12.)
The study includes a chart review of registered 0-6 year-old girls diagnosed with premature thelarche or precocious puberty from 1998 and until today at Dept. of Pediatrics A, AUH Skejby. The cohort has not earlier been examined and the number of girls in the cohort is estimated from our clinical experience with this patient group to be about 50 in total. The following characteristics from the patients records will be registered in a database:
Age at diagnosis, anthropometry (height and weight), Tanner stage - breast, Tanner stage - pubic hair, GnRH test (LH and FSH response), thyroid parameters, estrogen, prolactin, 17OHP, androstenedione, dihydroepiandrosteron (DHEA), testosterone, inhibin B, SHBG, AFP, kisspeptin, human chorionic gonadotropin (HCG), bone age, MRI of the cerebrum, US of internal genitalia, and exposures to environmental chemicals known to affect secondary sex characteristics.
The database will be developed in the program Access. The results will be reported as mean and standard deviation and minimum and maximum values for each age group by Tanner stage, if the data are normally distributed. Non-normally distributed data will be given as median and confidence intervals as well as minimum and maximum values for each Tanner stage. Data for previously studied children with suspected precocious puberty, will be reported in the same way. Statistical comparison between the groups will be made with u-paired t-test or equivalent non-parametric test, if the data is not normally distributed.
The Data Unit at Aarhus University Hospital, Skejby, identifies 0-6 year-old girls with diagnoses premature thelarche or precocious puberty in 1998 and onwards. Girls below 8 years of age at baseline of the project (1st of September 2013) will be contacted and requested to participate in a re-examination.
The follow-up is a clinical and paraclinical re-examination, where the following parameters are measured: anthropometry (height and weight), skinfold thickness, Tanner stage, bone age, GnRH test, p-estrogen, p-testosterone , p-SHBG, p- androstenedione, p-dihydroandrostendion, p-inhibin B, p-thyroid parameters, ultrasound examination of the genitalia interna and a blood sample for studies of polymorphism in the estrogen receptor gene and aromatase enzyme gene.
If the girls are unable or unwilling to attend the reexamination, they are requested to fill out a questionnaire instead as follows:
- name, social security number, date of completion the questionnaire
- current height, current weight, birth weight, origin
- date of onset of puberty if started, current pubertal development, menarche
- diseases/admissions
Regarding the mother:
- age at menarche, medicine during pregnancy/breastfeeding, diet during pregnancy/breastfeeding, use of cosmetics /cream/shampoo during pregnancy,
Regarding the family:
- others with early breast development/early puberty
The project is conducted at Dept. of Pediatrics A, Aarhus University Hospital, Skejby, Skejbygårdsvej 100, 8200 Aarhus N. The other pediatric wards in the Region of Midtjylland (located in Randers, Viborg and Herning) will be included in the project if they prefer to participate.
Study design
- Observational model
- Case only
- Target follow-up
- 1 Day
Who may qualify
- Ages
- Up to 8 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- 0-6 year old girls diagnosed with premature thelarche or precocious puberty from 1998 to today at the Children's Section A, AUH, Skejby. Girls who are 8 years old or under at baseline (1st of september) will be contacted and asked to participate in a clinical and paraclinical re-examination.
Key inclusion criteria (3 listed)
- Clinical diagnosis of precocious puberty or premature thelarche
- 0-6 year old girls at time of diagnosis for the medical record review
- 0-8 year old girls at baseline for the re-examination
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Tanner stage (breast and pubic hair)
Time frame: Up till age 21.0 years
6 secondary outcomes
weight
Time frame: up till age 21.0 years
height
Time frame: Up till age 21.0 years
Bone age
Time frame: Up till age 21.0 years
LH-peak after GnRH-test
Time frame: Up till age 21.0 years
Hormones (estrogen, prolactin, 17OHP, androstrendion, DHEA, testosterone, inhibin B, SHBG, AFP, kisspeptin, HCG, thyroid hormones)
Time frame: Up till age 21.0 years
Ultrasound of the internal genitalia
Time frame: Up till age 21.0 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Sep 2013.
- Background: PubMed 18509122Carel JC, Leger J. Clinical practice. Precocious puberty. N Engl J Med. 2008 May 29;358(22):2366-77. doi: 10.1056/NEJMcp0800459. No abstract available.
- Background: PubMed 15073143Carel JC, Lahlou N, Roger M, Chaussain JL. Precocious puberty and statural growth. Hum Reprod Update. 2004 Mar-Apr;10(2):135-47. doi: 10.1093/humupd/dmh012.
- Background: PubMed 16049645Tremblay L, Frigon JY. Precocious puberty in adolescent girls: a biomarker of later psychosocial adjustment problems. Child Psychiatry Hum Dev. 2005 Fall;36(1):73-94. doi: 10.1007/s10578-004-3489-2.
- Background: PubMed 16806671Michaud PA, Suris JC, Deppen A. Gender-related psychological and behavioural correlates of pubertal timing in a national sample of Swiss adolescents. Mol Cell Endocrinol. 2006 Jul 25;254-255:172-8. doi: 10.1016/j.mce.2006.04.037. Epub 2006 Jun 27.
- Background: PubMed 9093289Herman-Giddens ME, Slora EJ, Wasserman RC, Bourdony CJ, Bhapkar MV, Koch GG, Hasemeier CM. Secondary sexual characteristics and menses in young girls seen in office practice: a study from the Pediatric Research in Office Settings network. Pediatrics. 1997 Apr;99(4):505-12. doi: 10.1542/peds.99.4.505.
- Background: PubMed 16322154Teilmann G, Pedersen CB, Jensen TK, Skakkebaek NE, Juul A. Prevalence and incidence of precocious pubertal development in Denmark: an epidemiologic study based on national registries. Pediatrics. 2005 Dec;116(6):1323-8. doi: 10.1542/peds.2005-0012.
- Background: PubMed 19189683Houk CP, Kunselman AR, Lee PA. The diagnostic value of a brief GnRH analogue stimulation test in girls with central precocious puberty: a single 30-minute post-stimulation LH sample is adequate. J Pediatr Endocrinol Metab. 2008 Dec;21(12):1113-8. doi: 10.1515/jpem.2008.21.12.1113.
- Background: PubMed 22099730Curfman AL, Reljanovic SM, McNelis KM, Dong TT, Lewis SA, Jackson LW, Cromer BA. Premature thelarche in infants and toddlers: prevalence, natural history and environmental determinants. J Pediatr Adolesc Gynecol. 2011 Dec;24(6):338-41. doi: 10.1016/j.jpag.2011.01.003.
- Background: PubMed 21854448Atay Z, Turan S, Guran T, Furman A, Bereket A. The prevalence and risk factors of premature thelarche and pubarche in 4- to 8-year-old girls. Acta Paediatr. 2012 Feb;101(2):e71-5. doi: 10.1111/j.1651-2227.2011.02444.x. Epub 2011 Sep 23.
- Background: PubMed 19914634de Vries L, Guz-Mark A, Lazar L, Reches A, Phillip M. Premature thelarche: age at presentation affects clinical course but not clinical characteristics or risk to progress to precocious puberty. J Pediatr. 2010 Mar;156(3):466-71. doi: 10.1016/j.jpeds.2009.09.071. Epub 2009 Nov 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels H. Birkebæk, MD PhD principal investigator
Børneafdeling A, AUH, Skejby
Esben T. Vestergaard, MD, PhD principal investigator
Børneafdeling A, AUH, Skejby
Kurt Kristensen, MD, PhD principal investigator
Børneafdeling A, AUH, Skejby
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Precocious Puberty and Excess; Development, Breast, run by University of Aarhus at 2 sites in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Niels H Birkebæk, Dr.med, PhD (+45 50860090, nielbirk@rm.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tanner stage (breast and pubic hair) (time frame: Up till age 21.0 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01944475, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Sep 2013.