Constitutional Delay of Growth and Puberty: Towards Evidence-based Treatment

NCT01797718 | Completed Phase 2

• 1 other identifier: EudraCT:2012-002477-59
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 4

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.

Conditions

Constitutional Delay of Growth and Puberty

Keywords

Puberty; Constitutional; Delay; Letrozole; Testosterone

Outcome Measures

Primary Outcomes (2)

• testicular volume

  Testes will be measured with a ruler to the nearest millimeter and volume will be calculated at 0, 6, and 12 mo

  one year

• clinical and biochemical measures of pubertal progression

  Activity of the hypothalamic-pituitary-gonadal axis, evaluated by * genital and pubic hair stage of puberty according to Tanner; * growth velocity (cm/yr); * basal and gonadotropin-releasing hormone (GnRH)-stimulated gonadotropin levels; * urinary luteinizing hormone levels; * testosterone; * inhibin B; * anti-mullerian hormone (AMH)

  one year

Secondary Outcomes (3)

• Bone health

  one year

• Psychosocial well-being

  one year

• Puberty-related metabolical and clinical changes

  one year

Study Arms (2)

Testosterone

ACTIVE COMPARATOR

\~1mg/kg every 4 weeks for 6 months

Drug: Testosterone

Letrozole

ACTIVE COMPARATOR

2.5mg daily for 6 months

Drug: Letrozole

Interventions

Testosterone DRUG

1mg/kg every 4 weeks for 6 months

Also known as: Sustanon 250

Testosterone

Letrozole DRUG

2.5mg daily for 6 months. Safety criteria: if testosterone level is above 30nM at 3 months, the dosage is reduced to 2.5mg every other day

Also known as: Letrozole Bluefish, Letrozole Orion, Letrozole Accord, Letrozole Sandoz, Femar

Letrozole

Eligibility Criteria

• Age: 14 Years - 17 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Helsinki University Central Hospital: lead
• Foundation for Paediatric Research, Finland: collaborator

Study Sites (4)

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Kotka Central Hospital

Kotka, Finland

Location

Kuopio University Central Hospital

Kuopio, 70211, Finland

Location

Turku University Central Hospital

Turku, 20521, Finland

Location

Related Publications (5)

• Varimo T, Miettinen PJ, Huopio H, Rikkonen T, Voutilainen R, Tenhola S, Raivio T, Hero M. Impact of aromatase inhibition on bone mineral density and structure: a randomized controlled trial in boys with delayed puberty. Eur J Endocrinol. 2025 Jul 31;193(2):289-296. doi: 10.1093/ejendo/lvaf160.

  PMID: 40796279 DERIVED

• Kariola L, Varimo T, Huopio H, Tenhola S, Voutilainen R, Kosola S, Toppari J, Sintonen H, Miettinen PJ, Raivio T, Hero M. Health-related quality of life in boys with constitutional delay of growth and puberty. Front Endocrinol (Lausanne). 2022 Nov 25;13:1028828. doi: 10.3389/fendo.2022.1028828. eCollection 2022.

  PMID: 36518253 DERIVED

• 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.

  PMID: 34596269 DERIVED

• 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.

  PMID: 31958337 DERIVED

• 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.

  PMID: 30612946 DERIVED

MeSH Terms

Interventions

Testosterone; Letrozole

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Taneli Raivio, MD, PhD

  Helsinki University Central Hospital

  PRINCIPAL INVESTIGATOR

• Matti Hero, MD, PhD

  Helsinki University Central Hospital

  STUDY DIRECTOR

• Tero Varimo, MD, PhD

  Helsinki University Central Hospital

  STUDY CHAIR

• Päivi Miettinen, MD, PhD

  Helsinki University Central Hospital

  STUDY CHAIR

• Jorma Toppari, MD, PhD

  University of Turku

  STUDY CHAIR

• Hanna Huopio, MD, PhD

  Kuopio University Central Hospital

  STUDY CHAIR

• Sirpa Tenhola, MD, PhD

  Kymeenlaakso Central Hospital

  STUDY CHAIR

• Raimo Voutilainen, MD, PhD

  Kuopio University Central Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 18, 2013
• First Posted: February 22, 2013
• Study Start: October 1, 2013
• Primary Completion: March 20, 2017
• Study Completion: February 5, 2018
• Last Updated: February 6, 2018

Record last verified: 2018-02

Locations

FI (4)