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Trials
Published in: Trials 1/2023

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

SPIOMET4HEALTH—efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial

Authors: Cristina Garcia-Beltran, Rita Malpique, Marianne S. Andersen, Firdevs Bas, Judit Bassols, Feyza Darendeliler, Marta Díaz, Barbara Dieris, Flaminia Fanelli, Elke Fröhlich-Reiterer, Alessandra Gambineri, Dorte Glintborg, Abel López-Bermejo, Christopher Mann, Silvia Marin, Barbara Obermayer-Pietsch, Rønnaug Ødegård, Pernille Ravn, Thomas Reinehr, Matteo Renzulli, Cristina Salvador, Viola Singer, Eszter Vanky, Juan Vicente Torres, Melek Yildiz, Francis de Zegher, Lourdes Ibáñez

Published in: Trials | Issue 1/2023

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Abstract

Background

Polycystic ovary syndrome (PCOS) is the most prevalent, chronic endocrine-metabolic disorder of adolescents and young women (AYAs), affecting 5–10% of AYAs worldwide. There is no approved pharmacological therapy for PCOS. Standard off-label treatment with oral contraceptives (OCs) reverts neither the underlying pathophysiology nor the associated co-morbidities. Pilot studies have generated new insights into the pathogenesis of PCOS, leading to the development of a new treatment consisting of a fixed, low-dose combination of two so-called insulin sensitisers [pioglitazone (PIO), metformin (MET)] and one mixed anti-androgen and anti-mineralocorticoid also acting as an activator of brown adipose tissue [spironolactone (SPI)], within a single tablet (SPIOMET). The present trial will evaluate the efficacy, tolerability and safety of SPIOMET, on top of lifestyle measures, for the treatment of PCOS in AYAs.

Methods

In this multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial, AYAs with PCOS will be recruited from 7 clinical centres across Europe. Intention is to randomise a total of 364 eligible patients into four arms (1:1:1:1): Placebo, PIO, SPI + PIO (SPIO) and SPI + PIO + MET (SPIOMET). Active treatment over 12 months will consist of lifestyle guidance plus the ingestion of one tablet daily (at dinner time); post-treatment follow-up will span 6 months. Primary endpoint is on- and post-treatment ovulation rate. Secondary endpoints are clinical features (hirsutism, menstrual regularity); endocrine-metabolic variables (androgens, lipids, insulin, inflammatory markers); epigenetic markers; imaging data (carotid intima-media thickness, body composition, abdominal fat partitioning, hepatic fat); safety profile; adherence, tolerability and acceptability of the medication; and quality of life in the study participants. Superiority (in this order) of SPIOMET, SPIO and PIO will be tested over placebo, and if present, subsequently the superiority of SPIOMET versus PIO, and if still present, finally versus SPIO.

Discussion

The present study will be the first to evaluate—in a randomised, double-blind, placebo-controlled way—the efficacy, tolerability and safety of SPIOMET treatment for early PCOS, on top of a lifestyle intervention.

Trial registration

EudraCT 2021–003177-58. Registered on 22 December 2021.
Appendix
Available only for authorised users
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Metadata
Title
SPIOMET4HEALTH—efficacy, tolerability and safety of lifestyle intervention plus a fixed dose combination of spironolactone, pioglitazone and metformin (SPIOMET) for adolescent girls and young women with polycystic ovary syndrome: study protocol for a multicentre, randomised, double-blind, placebo-controlled, four-arm, parallel-group, phase II clinical trial
Authors
Cristina Garcia-Beltran
Rita Malpique
Marianne S. Andersen
Firdevs Bas
Judit Bassols
Feyza Darendeliler
Marta Díaz
Barbara Dieris
Flaminia Fanelli
Elke Fröhlich-Reiterer
Alessandra Gambineri
Dorte Glintborg
Abel López-Bermejo
Christopher Mann
Silvia Marin
Barbara Obermayer-Pietsch
Rønnaug Ødegård
Pernille Ravn
Thomas Reinehr
Matteo Renzulli
Cristina Salvador
Viola Singer
Eszter Vanky
Juan Vicente Torres
Melek Yildiz
Francis de Zegher
Lourdes Ibáñez
Publication date
01-12-2023
Publisher
BioMed Central
Published in
Trials / Issue 1/2023
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/s13063-023-07593-6

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