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Open Access 01-12-2023 | Spironolactone | Study protocol

Effects of half-dose spiomet treatment in girls with early puberty and accelerated bone maturation: a multicenter, randomized, placebo-controlled study protocol

Authors: Judit Bassols, Francis de Zegher, Marta Diaz, Gemma Carreras-Badosa, Cristina Garcia-Beltran, Elsa Puerto-Carranza, Cora Oliver-Vila, Paula Casano, Céline Alicia Franco, Rita Malpique, Abel López-Bermejo, Lourdes Ibáñez

Published in: Trials | Issue 1/2023

Abstract

Background

A “mismatch” sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in “mismatch” girls with early puberty.

Methods

Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0–9.5 years; birthweight (BW) for gestational age: −2.5 < Z-score <0, body mass index (BMI): 0 < Z-score < +2.5 and early progressive puberty (Tanner B2 at 7.7–9.3 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in “mismatch” adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. Interventions: randomization (1:1) for placebo vs mini-spiomet. Primary outcome: annualized bone age advancement (0–1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat.

Discussion

The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight.

Trial registration

EudraCT 2021-006766-21. Registered on May 30, 2022.

Available only for authorised users

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Title: Effects of half-dose spiomet treatment in girls with early puberty and accelerated bone maturation: a multicenter, randomized, placebo-controlled study protocol
Authors: Judit Bassols
Francis de Zegher
Marta Diaz
Gemma Carreras-Badosa
Cristina Garcia-Beltran
Elsa Puerto-Carranza
Cora Oliver-Vila
Paula Casano
Céline Alicia Franco
Rita Malpique
Abel López-Bermejo
Lourdes Ibáñez
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Spironolactone
Polycystic Ovary Syndrome
Pioglitazone
Metformin
Polycystic Ovary Syndrome
Published in: Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-022-07050-w

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Effects of half-dose spiomet treatment in girls with early puberty and accelerated bone maturation: a multicenter, randomized, placebo-controlled study protocol

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

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