NCT05957991

Brief Summary

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.

Trial Health

63
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,500

participants targeted

Target at P75+ for all trials

Timeline
52mo left

Started Sep 2023

Longer than P75 for all trials

Geographic Reach
1 country

5 active sites

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress38%
Sep 2023Sep 2030

First Submitted

Initial submission to the registry

July 14, 2023

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 24, 2023

Completed
1 month until next milestone

Study Start

First participant enrolled

September 1, 2023

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 30, 2026

Expected
4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2030

Last Updated

July 24, 2023

Status Verified

July 1, 2023

Enrollment Period

3 years

First QC Date

July 14, 2023

Last Update Submit

July 14, 2023

Conditions

Keywords

Puberty

Outcome Measures

Primary Outcomes (5)

  • 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

    3 years

  • BMI (SDS) at pubertal onset

    Adiposity in children with precocious puberty

    3 years

  • Genome-wide methylation patterns in peripheral blood associated with CPP and treatment

    epigenetic alterations

    3 years

  • Urinary EDC excretion profiles in CPP children compared to age-matched controls

    endocrine disrupting chemicals associated to early puberty

    3 years

  • Randomised placebo controlled trial

    The effect of metformin and/or lifestyle intervention on pubertal development

    3 years

Study Arms (4)

Met -lifestyle intervention

Girls with overweight and early puberty aged 8-9 years Treatment with metformin without lifestyle intervention (diet, training)

Drug: Metformin Hydrochloride tabletBehavioral: No lifestyle intervention

Met + lifestyle intervention

Girls with overweight and early puberty aged 8-9 years Treatment with metformin with lifestyle intervention (diet, training)

Drug: Metformin Hydrochloride tabletBehavioral: Lifestyle intervention

Placebo-lifestyle intervention

Girls with overweight and early puberty aged 8-9 years Treatment with placebo without lifestyle intervention (diet, training)

Drug: PlaceboBehavioral: No lifestyle intervention

Placebo+lifestyle intervention

Girls with overweight and early puberty aged 8-9 years Treatment with placebo with lifestyle intervention (diet, training)

Drug: PlaceboBehavioral: Lifestyle intervention

Interventions

Treatment with metformin

Also known as: Metformin
Met + lifestyle interventionMet -lifestyle intervention

Treatment with placebo

Placebo+lifestyle interventionPlacebo-lifestyle intervention

Changing behaviour on diet and excersise

Met + lifestyle interventionPlacebo+lifestyle intervention

No changes in behaviou on diet and excersise

Met -lifestyle interventionPlacebo-lifestyle intervention

Eligibility Criteria

Age3 Years - 10 Years
Sexall
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study 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.

You may qualify if:

  • All children (\> 4 years of age) referred to one of the seventeen collaborating pediatric departments with one of the following diagnosis (ICD10)
  • DE301
  • DE228A
  • DE308A
  • DE270B
  • DE308
  • DE309
  • DZ003

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Copenhagen University Hospital - Herlev

Herlev, Capital Region, 2730, Denmark

Location

Univerity Hospital Aalborg

Aalborg, Denmark

Location

University Hospital Aarhus

Aarhus, Denmark

Location

University Hospital Odense

Odense, Denmark

Location

University Hospital Roskilde

Roskilde, Denmark

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood sample for hormone analysis, genetic and epigenetic analysis Urine sample analysis of endocrine disrupting chemicals

MeSH Terms

Conditions

Puberty, Precocious

Interventions

Metformin

Condition Hierarchy (Ancestors)

Gonadal DisordersEndocrine System Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Central Study Contacts

Rikke B Jensen, MD PhD

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
2 Years
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor PhD

Study Record Dates

First Submitted

July 14, 2023

First Posted

July 24, 2023

Study Start

September 1, 2023

Primary Completion (Estimated)

August 30, 2026

Study Completion (Estimated)

September 1, 2030

Last Updated

July 24, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will share

Data collected in the study may be provided to qualified researchers with academic interest in precocious puberty. Shared data will be coded, with no protected health information included. Approval of the request are prerequisites to the sharing of data with the requesting party. Access to trial IPD can be requested by qualified researchers engaging in scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)

Shared Documents
STUDY PROTOCOL, SAP, ICF
Time Frame
Data requests may be submitted from 12 to 24 months after publication of the article.
Access Criteria
Access to trial IPD can be requested by qualified researchers engaging in scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA)

Locations