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

Trials

Study Protocol

Christopher Mann¹  Rønnaug Ødegård²  Eszter Vanky³  Marianne S. Andersen⁴  Dorte Glintborg⁴  Pernille Ravn⁴  Flaminia Fanelli⁵  Alessandra Gambineri⁵  Thomas Reinehr⁶  Viola Singer⁶  Barbara Dieris⁶  Matteo Renzulli⁷  Barbara Obermayer-Pietsch⁸  Elke Fröhlich-Reiterer⁹  Francis de Zegher^1,10  Judit Bassols^1,11  Juan Vicente Torres^1,12  Abel López-Bermejo^1,13  Cristina Salvador^1,14  Silvia Marin^1,14  Rita Malpique^1,15  Cristina Garcia-Beltran^1,15  Lourdes Ibáñez^1,15  Marta Díaz^1,15  Firdevs Bas^1,16  Feyza Darendeliler^1,16  Melek Yildiz^1,16 

[1] Asphalion, Barcelona, Spain;Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Centre for Obesity Research, St. Olavs Hospital, Trondheim University Hospital, Torgarden, Trondheim, Norway;Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;Department of Obstetrics and Gynaecology, St. Olavs Hospital, Trondheim University Hospital, 7006, Trondheim, Norway;Department of Gynaecology and Obstetrics and Department of Endocrinology, University of Southern Denmark, Odense University Hospital, Odense, Denmark;Department of Medical and Surgical Science-DIMEC, Division of Endocrinology and Diabetes Prevention and Care, University of Bologna - S. Orsola-Hospital, Bologna, Italy;Department of Paediatric Endocrinology, Diabetes and Nutrition Medicine, Vestische Hospital for Children and Adolescents Datteln, University of Witten-Herdecke, Datteln, Germany;Department of Radiology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy;Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria;Division of General Paediatrics, Department of Paediatrics and Adolescent Medicine, Medical University of Graz, Graz, Austria;Leuven Research & Development, University of Leuven, 3000, Louvain, Belgium;Maternal-Fetal Metabolic Research Group, Girona Institute for Biomedical Research (IDIBGI), Girona, Spain;Optimapharm, Palma de Mallorca, Palma, Spain;Paediatric Endocrinology Research Group, Girona Institute for Biomedical Research (IDIBGI), Paediatrics, Dr. Josep Trueta Hospital, Department of Medical Sciences, University of Girona, Girona, Spain;Paediatric Endocrinology, Paediatric Research Institute Sant Joan de Déu, University of Barcelona, 08950, Esplugues, Barcelona, Spain;Paediatric Endocrinology, Paediatric Research Institute Sant Joan de Déu, University of Barcelona, 08950, Esplugues, Barcelona, Spain;Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), ISCIII, 28029, Madrid, Spain;Pediatric Endocrinology Unit, Istanbul University, Istanbul, Turkey;

关键词: Androgen excess;    Polycystic ovary syndrome;    PCOS;    Ectopic fat;    Liver fat;    Central obesity;    Anovulation;    Pioglitazone;    Spironolactone;    Metformin;   

DOI  :  10.1186/s13063-023-07593-6

 received in 2023-08-03, accepted in 2023-08-17,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundPolycystic 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.MethodsIn 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.DiscussionThe 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 registrationEudraCT 2021–003177-58. Registered on 22 December 2021.https://www.clinicaltrialsregister.eu/ctr-search/search?query=%092021-003177-58.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

【 图 表 】

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