Evaluating a new treatment for Polycystic Ovary Syndrome in young women

A Phase II, Randomised, Multi-centric, Multi-national Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of a Fixed Dose Combination of Spironolactone, Pioglitazone & Metformin (SPIOMET) for Adolescent Girls and Young Adult Women (AYAs) With Polycystic Ovary Syndrome (PCOS)

This study is testing a new combination treatment for young women with Polycystic Ovary Syndrome to see if it can improve their symptoms and overall health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 364 (estimated)
• Ages: 12 Years to 23 Years
• Sex: Female
• Sponsor: Fundació Sant Joan de Déu (Academic / other)
• Locations: 7 sites (Graz and 6 other locations)
• Trial ID: NCT05394142 on ClinicalTrials.gov

What this trial studies

This clinical trial is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II evaluation of a fixed dose combination of Spironolactone, Pioglitazone, and Metformin (SPIOMET) for adolescent girls and young adult women with Polycystic Ovary Syndrome (PCOS). The study aims to assess the efficacy, tolerability, and safety of this combination therapy, which is designed to address the underlying pathophysiology of PCOS rather than just alleviating symptoms. Participants will be monitored for improvements in symptoms and overall health outcomes associated with PCOS.

Who should consider this trial

Good fit: Ideal candidates for this study are adolescent girls and young adult women aged 12 to 23.9 years with clinical signs of androgen excess, such as hirsutism or inflammatory acne.

Not a fit: Patients who do not meet the age criteria or those without clinical signs of androgen excess may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a more effective and safer option for managing PCOS in young women, potentially reversing the condition's underlying causes.

How similar studies have performed: While there is limited data on this specific combination therapy, previous studies have shown promise in using similar approaches to treat PCOS.

Eligibility criteria

Inclusion Criteria:

1. Age range within the AYAs category (\> 12.0 years and ≤ 23.9 years at study start) (96); Given that another inclusion criterium is gynaecological age (years elapsed since menarche) of 2 years or more, and that menarche before age 10.0 years is an exclusion criterium (please see exclusion criteria below), the youngest participant will be older than 12.0 years at study start (97). The upper age limit at study start is set at 23.9 years (thus, 24.9 years when the active treatment ends, see section 7. Conduct), in order to avoid early dropouts due to an increase in the prevalence of pregnancy wish beyond that age in most European countries;
2. Gynaecological age of 2 years or more;
3. Clinical androgen excess, as defined by the presence of hirsutism (modified Ferriman-Gallwey score ≥ 4) (17,98) and/or inflammatory acne (Leeds scale) unresponsive to medications (3,95,99). The scarce normative data existing in adolescents suggest that an adult level of hirsutism is reached around 2 years after menarche (100);
4. Biochemical androgen excess, as defined by increased total testosterone (≥50 ng/dL), and/or a FAI higher than 3.5 \[FAI, total testosterone (nmol/L) x 100/SHBG (nmol/L)\], in the follicular phase of the cycle (days 3-7) or after 2 months of amenorrhea (3,100,101); Measurements of total testosterone and/or FAI are the most recommended assessments to screen for hyperandrogenaemia (3,19,95,102). Serum testosterone attains adult levels shortly after menarche; thus, an elevation of serum testosterone concentrations and/or FAI above adult norms and assessed in reliable reference laboratories constitutes biochemical evidence of hyperandrogenism (3,19,95,100). It is accepted that this upper limit can be set at 45 ng/dL for testosterone and at 3.5 for FAI (3,95,100,101,102,103). Direct free testosterone assays, such as radiometric or enzyme-linked assays, preferably should not be used in the assessment of biochemical hyperandrogenism, as they demonstrate poor sensitivity, accuracy and precision (17);
5. Menstrual irregularity, as defined by ≤ 8 menses per year corresponding to an average inter-menstrual time of ≥45 days (3,95,100); Most adolescents establish a menstrual interval of 20-45 days within the first 2 years after menarche (3,95). Three years after menarche, the 95th percentile for cycle length is 43.6 days (104); thus, cycles longer than 45 days (\<8 periods/year) at or beyond this gynaecological age are considered abnormal and are evidence of oligo-anovulation;
6. Written informed consent obtained from the patient, or assent from the patient and consent by the parents or the legally acceptable representative if she is a minor (for details, see section 7. Conduct, under informed consent).

Exclusion Criteria:

-

Where this trial is running

Graz and 6 other locations

• Universitätsklinik für Innere Medizin — Graz, Austria (Recruiting)
• Odense University Hospital (UNIODE) — Odense, Denmark (Recruiting)
• Azienda Ospedaliero Universitaria di Bologna — Bologna, Italy (Recruiting)
• St. Olavs Hospital — Trondheim, Norway (Recruiting)
• Hospital Sant Joan de Deu — Esplugues De Llobregat, Spain (Recruiting)
• Hospital Universitari de Girona Dr. Trueta — Girona, Spain (Recruiting)
• İstanbul Faculty of Medicine Topkapı — Istanbul, Turkey (Recruiting)

Study contacts

• Principal investigator: Lourdes Ibañez, MD, PhD — Investigator
• Study coordinator: Rita Malpique, PhD

Conditions Polycystic Ovary Syndrome; polycystic ovary syndrome; spironolactone; pioglitazone; metformin; peadiatric; PCOS