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

被引：2

作者：

Garcia-Beltran, Cristina ^{[1
,2
]}

Malpique, Rita ^{[1
,2
]}

Andersen, Marianne S. ^{[3
,4
]}

Bas, Firdevs ^{[5
]}

Bassols, Judit ^{[6
]}

Darendeliler, Feyza ^{[5
]}

Diaz, Marta ^{[1
,2
]}

Dieris, Barbara ^{[7
]}

Fanelli, Flaminia ^{[8
]}

Froehlich-Reiterer, Elke ^{[9
]}

Gambineri, Alessandra ^{[8
]}

Glintborg, Dorte ^{[3
,4
]}

Lopez-Bermejo, Abel ^{[10
]}

Mann, Christopher ^{[11
]}

Marin, Silvia ^{[1
]}

Obermayer-Pietsch, Barbara ^{[12
]}

Odegard, Ronnaug ^{[13
,14
]}

Ravn, Pernille ^{[3
,4
]}

Reinehr, Thomas ^{[7
]}

Renzulli, Matteo ^{[15
]}

Salvador, Cristina ^{[1
]}

Singer, Viola ^{[7
]}

Vanky, Eszter ^{[13
,16
]}

Torres, Juan Vicente ^{[17
]}

Yildiz, Melek ^{[5
]}

de Zegher, Francis ^{[18
]}

Ibanez, Lourdes ^{[1
,2
]}

机构：

[1] Univ Barcelona, Paediat Res Inst St Joan de Deu, Paediat Endocrinol, Barcelona 08950, Spain

[2] ISCIII, Ctr Invest Biomed Red Diabet & Enfermedades Metab, Madrid 28029, Spain

[3] Univ Southern Denmark, Odense Univ Hosp, Dept Gynaecol & Obstet, Odense, Denmark

[4] Univ Southern Denmark, Odense Univ Hosp, Dept Endocrinol, Odense, Denmark

[5] Istanbul Univ, Pediat Endocrinol Unit, Istanbul, Turkiye

[6] Girona Inst Biomed Res IDIBGI, Maternal Fetal Metab Res Grp, Girona, Spain

[7] Univ Witten Herdecke, Vest Hosp Children & Adolescents Datteln, Dept Paediat Endocrinol Diabet & Nutr Med, Datteln, Germany

[8] Univ Bologna, S Orsola Hosp, Dept Med & Surg Sci DIMEC, Div Endocrinol & Diabet Prevent & Care, Bologna, Italy

[9] Med Univ Graz, Dept Paediat & Adolescent Med, Div Gen Paediat, Graz, Austria

[10] Univ Girona, Dr Josep Trueta Hosp, Girona Inst Biomed Res IDIBGI, Paediat Endocrinol Res Grp,Dept Med Sci,Paediat, Girona, Spain

[11] Asphalion, Barcelona, Spain

[12] Med Univ Graz, Dept Internal Med, Div Endocrinol & Diabetol, Graz, Austria

[13] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway

[14] Trondheim Reg & Univ Hosp, St Olavs Hosp, Ctr Obes Res, Trondheim, Norway

[15] IRCCS Azienda Osped Univ Bologna, Dept Radiol, Bologna, Italy

[16] Univ Trondheim Hosp, St Olavs Hosp, Dept Obstet & Gynaecol, N-7006 Trondheim, Norway

[17] Optimapharm, Palma De Mallorca, Palma, Spain

[18] Univ Leuven, Leuven Res & Dev, B-3000 Louvain, Belgium

来源：

TRIALS | 2023年 / 24卷 / 01期

关键词：

Androgen excess; Polycystic ovary syndrome; PCOS; Ectopic fat; Liver fat; Central obesity; Anovulation; Pioglitazone; Spironolactone; Metformin; INTIMA-MEDIA THICKNESS; NONOBESE ADOLESCENTS; ANDROGEN EXCESS; ETHINYLESTRADIOL-DROSPIRENONE; INSULIN-RESISTANCE; OVULATION RATE; KEY ROLE; FLUTAMIDE; RISK; HYPERANDROGENISM;

D O I：

10.1186/s13063-023-07593-6

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

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

引用

页数：25

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