Clinical trial NCT01797718: Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment
Official title: Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Constitutional Delay of Growth and Puberty
Keywords: Puberty
Constitutional
Delay
Letrozole
Testosterone
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Foundation for Paediatric Research, Finland
First posted: 2013-02-22
Enrollment: 35
Sex: MALE
Minimum age (years): 14
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Boys with constitutional delay of growth and puberty (CDGP) should be offered evidence-based effective and safe treatment option. This study compares the effects of low-dose testosterone and aromatase inhibitor letrozole on pubertal progression. The hypothesis is that, in boys CDGP showing earliest signs of puberty, peroral letrozole (2.5 mg/d for 6 mo) induces faster biochemical and clinical progression of puberty as compared to low-dose intramuscular testosterone Rx (\~1mg/kg/mo for 6 mo). In addition, 10 or more boys who select watchful waiting instead of medication will provide background data on the natural progression of CDGP, and their data will not be used in primary statistical comparisons.


Eligibility criteria: Inclusion Criteria:

* Constitutional delay of growth and puberty
* Age 14 years or more
* mean testicular volume 2.5 ml or more and less than 4 ml
* serum testosterone level less than 5 nM OR

as above, but serum testosterone 1 nM or more with normal DHEAS level, even if the mean testicular volume is less than 2.5 ml OR

as above, but tanner stage G2 and testosterone level less than 3 nM

Exclusion Criteria:

* Chronic diseases
* Primary or secondary hypogonadism
* Chromosomal anomalies
* Chronic medication that potentially adversely affects bone mineralization (excluding inhaled corticosteroid treatment)

Primary outcomes:
measure: testicular volume
timeFrame: one year
measure: clinical and biochemical measures of pubertal progression
timeFrame: one year
Secondary outcomes:
measure: Bone health
timeFrame: one year
measure: Psychosocial well-being
timeFrame: one year
measure: Puberty-related metabolical and clinical changes
timeFrame: one year
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Kotka
country: Finland
facility: Kotka Central Hospital
city: Kuopio
country: Finland
facility: Kuopio University Central Hospital
city: Turku
country: Finland
facility: Turku University Central Hospital
Study officials:
affiliation: Helsinki University Central Hospital
name: Taneli Raivio, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Helsinki University Central Hospital
name: Matti Hero, MD, PhD
role: STUDY_DIRECTOR
affiliation: Helsinki University Central Hospital
name: Tero Varimo, MD, PhD
role: STUDY_CHAIR
affiliation: Helsinki University Central Hospital
name: Päivi Miettinen, MD, PhD
role: STUDY_CHAIR
affiliation: University of Turku
name: Jorma Toppari, MD, PhD
role: STUDY_CHAIR
affiliation: Kuopio University Central Hospital
name: Hanna Huopio, MD, PhD
role: STUDY_CHAIR
affiliation: Kymeenlaakso Central Hospital
name: Sirpa Tenhola, MD, PhD
role: STUDY_CHAIR
affiliation: Kuopio University Central Hospital
name: Raimo Voutilainen, MD, PhD
role: STUDY_CHAIR
References:
citation: Huttunen H, Varimo T, Huopio H, Voutilainen R, Tenhola S, Miettinen PJ, Raivio T, Hero M. Serum testosterone and oestradiol predict the growth response during puberty promoting treatment. Clin Endocrinol (Oxf). 2022 Feb;96(2):220-226. doi: 10.1111/cen.14605. Epub 2021 Oct 1.
citation: Kohva E, Varimo T, Huopio H, Tenhola S, Voutilainen R, Toppari J, Miettinen PJ, Vaaralahti K, Viinamaki J, Backman JT, Hero M, Raivio T. Anti-Mullerian hormone and letrozole levels in boys with constitutional delay of growth and puberty treated with letrozole or testosterone. Hum Reprod. 2020 Feb 29;35(2):257-264. doi: 10.1093/humrep/dez231.
citation: Varimo T, Huopio H, Kariola L, Tenhola S, Voutilainen R, Toppari J, Toiviainen-Salo S, Hamalainen E, Pulkkinen MA, Laaperi M, Tarkkanen A, Vaaralahti K, Miettinen PJ, Hero M, Raivio T. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019 Feb;3(2):109-120. doi: 10.1016/S2352-4642(18)30377-8. Epub 2019 Jan 4.