About this trial
There is an urgent need to obtain more knowledge about the influence of weight and metabolism on the timing and progression of puberty. The age of pubertal onset has been constantly declining during the last decades and extremely early maturation may have yet unseen consequences for the psychosocial development of the child as well as detrimental long-term health consequences. Studies have shown that girls with early-onset puberty are more likely than their peers to enter sexual relationships at a younger age, to experience more psychological distress, and to engage in risk-taking behaviors. In addition, early maturation may have long-term health consequences since earlier menarche is associated with an increased risk of all-cause mortality and cardiovascular disease later in life in large epidemiological studies. The exact aetiology for the earlier onset of puberty in the general population remains to be elucidated, and the cause is probably to be found in a complex interplay between genetic, epigenetic, environmental and metabolic factors. However, world-wide there is a concerning increasing prevalence of overweight in childhood and early puberty is one of many consequences of this. Environmental factors such as endocrine disrupting chemicals have been suggested to play a role for both obesity and precocious puberty either directly or through epigenetic moderation. The current study of a Danish National cohort will explore the incidence and aetiology of precocious puberty for better treatment and prevention. Furthermore, a placebo-controlled randomized controlled trial may give a novel mechanistic insight of the interplay between insulin sensitivity and sex steroids. To our knowledge this study is the first of its kind and may lead to novel alternative treatment strategy for overweight girls with early puberty that may have beneficial effects on long-term morbidity and mortality.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
DE301
DE228A
DE308A
DE270B
Disqualifiers
If the investigating doctor at the local hospital observes unexpected psychological/physical reactions, or a participant is found to be unsuitable (cf. inclusion criteria) or regrets agreeing to participate, this person can at any given time be excluded.
Trial population
Seventeen pediatric hospital departments in Denmark will be included and an expected more than 1,500 children referred for early puberty will be invited to participate in the study. Since this cohort consists of patients who are going through the examinations and blood samples as part of the routine clinical work-up for CPP we expect a high participation rate around 70-80%. The patients are asked for a fasting blood sample and a urine sample for the clinical biobank. It is essential to include all departments to evaluate the incidence of precocious puberty in Denmark and to ensure power for the analyses of etiology.
Trial design
Cohort
Prospective
Treatments tested in this trial
Metformin Hydrochloride tablet
DrugTreatment with metformin
Placebo
DrugTreatment with placebo
Lifestyle intervention
BehavioralChanging behaviour on diet and excersise
No lifestyle intervention
BehavioralNo changes in behaviou on diet and excersise
Treatment groups
Trial outcomes
Primary outcomes
Incidence of CPP among all children referred to 18 Danish pediatric departments during a 3-year period
Number of patients referred who have precocious puberty
BMI (SDS) at pubertal onset
Adiposity in children with precocious puberty
Genome-wide methylation patterns in peripheral blood associated with CPP and treatment
epigenetic alterations
Urinary EDC excretion profiles in CPP children compared to age-matched controls
endocrine disrupting chemicals associated to early puberty
Sponsors and contacts
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