Polycystic Ovary Syndrome (PCOS)Phase 2SPIOMET4HEALTHNCT05394142
A Clinical Trial to Evaluate the Efficacy, Tolerability, and Safety of a Fixed Dose Combination of Spironolactone, Pioglitazone & Metformin (SPIOMET) in Polycystic Ovary Syndrome (PCOS)
A Phase 2 study testing Pioglitazone, Spironolactone and Metformin in people with Polycystic Ovary Syndrome (PCOS), run by Fundació Sant Joan de Déu at 7 sites in 6 countries.
Trial summary
This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women with polycystic… Read more about this study
- Who is it for?
- Ages 12 to 23 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome (PCOS)
- What is being tested?
- Pioglitazone, Spironolactone and Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 364 participants
- Where
- 7 sitesin 6 countries
- Study dates
- 24 May 2022to Apr 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 23 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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;
- Gynaecological age of 2 years or more;
- 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);
- 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);
- 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;
- 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).
Who cannot join
- -
Trial locations and contacts
7 sites in 6 countries.
Elizabeth García Pérez, PhD contact
7 sites in 6 countries
Spain2 sites, 2 recruiting
- Recruiting
Hospital Sant Joan de Deu
Esplugues de Llobregat
Lourdes Ibañez
- Recruiting
Hospital Universitari de Girona Dr. Trueta
Girona
Abel López Bermejo
Austria1 site, 1 recruiting
- Recruiting
Universitätsklinik für Innere Medizin
Graz
Barbara Obermayer-Pietsch
Denmark1 site, 1 recruiting
- Recruiting
Odense University Hospital (UNIODE)
Odense
Pernille Ravn
Italy1 site, 1 recruiting
- Recruiting
Azienda Ospedaliero Universitaria di Bologna
Bologna
Alessandra Gambineri
Turkey (Türkiye)1 site, 1 recruiting
- Recruiting
İstanbul Faculty of Medicine Topkapı
Istanbul
Feyza Darendeliler
About this study
Official title: 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 is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women with polycystic ovary syndrome.
Study description: Currently, there is no European Medicines Agency /U.S. Food and Drug Administration (FDA)-approved therapy for polycystic ovary syndrome in adolescent girls and young adult women. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of AYAs with PCOS, including those without pregnancy risk. OCs alleviate key symptoms by inducing a pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin (SHBG), but OCs do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility and possibly, for lifelong co-morbidities.
Read more
Given the key role of hepato-visceral fat excess in the pathogenesis of PCOS, the prime aim of the treatment should be to achieve a preferential loss of central fat, which should in turn normalise the entire PCOS phenotype. Recent evidence disclosed that a treatment consisting of a fixed low-dose combination of two insulin sensitisers [pioglitazone (PIO) and metformin (MET), with different modes of action], and one mixed anti-androgen and anti-mineralocorticoid (spironolactone), was superior to an OC in normalising the PCOS phenotype, including ovulation rates and hepato-visceral fat.
The study's main goals are to assess the efficacy, tolerability and safety of a new treatment (SPIOMET) for adolescent girls and young adult women with polycistic ovarian syndrome; the comparison (in this order) of each SPIOMET, spironolactone and pioglitazone (SPIO) and PIO over placebo; and in addition, the comparison of SPIOMET over PIO and over SPIO (in this order).
Primary Objective: To test the efficacy of SPIOMET in normalising ovulation rate in adolescents and young adult women with PCOS.
Secondary Objectives: To test the efficacy of SPIOMET in normalising the endocrine-metabolic status, to describe the drug safety profile and to assess the adherence and subjective acceptability, as well as the quality of life of the participating subjects.
Read the detailed description
This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women (AYAs) with polycystic ovary syndrome (PCOS).
Study description: Currently, there is no European Medicines Agency (EMA)/U.S. Food and Drug Administration (FDA)-approved therapy for PCOS in AYAs. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of AYAs with PCOS, including those without pregnancy risk. OCs alleviate key symptoms by inducing a pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin (SHBG), but OCs do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility and possibly, for lifelong co-morbidities.
Given the key role of hepato-visceral fat excess in the pathogenesis of PCOS, the prime aim of the treatment should be to achieve a preferential loss of central fat, which should in turn normalise the entire PCOS phenotype. Recent evidence disclosed that a treatment consisting of a fixed low-dose combination of two insulin sensitisers [pioglitazone (PIO) and metformin (MET), with different modes of action], and one mixed anti-androgen and anti-mineralocorticoid (spironolactone), was superior to an OC in normalising the PCOS phenotype, including ovulation rates and hepato-visceral fat.
- Conditions
- Polycystic Ovary Syndrome (PCOS)
- Being tested
- Placebo, Pioglitazone, Spironolactone, Metformin
- Keywords
- polycystic ovary syndrome, spironolactone, pioglitazone, metformin, peadiatric, PCOS
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Comparator arm with placebo
PioglitazoneDrug
Also called PIO
Pioglitazone 7.5 mg/day
SpironolactoneDrug
Also called S
Spironolactone 50 mg/day
MetforminDrug
Also called MET
Metformin 850 mg/day
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 - Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
| Arm 1 - PIO | Experimental | Pioglitazone Receives: Drug: Pioglitazone |
| Arm 1 - SPIO | Experimental | Spironolactone and Pioglitazone Receives: Drug: Pioglitazone; Drug: Spironolactone |
| Arm 1 - SPIOMET | Experimental | Spironolactone, Pioglitazone and Metformin Receives: Drug: Pioglitazone; Drug: Spironolactone; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
On-treatment ovulation rate.
On-treatment ovulation rate.
Measured: Following end of each two 12-week on-treatment periods (month 0-3 and month 9-12)
Post-treatment ovulation rate.
Post-treatment ovulation rate.
Measured: Following the end of post-treatment period (month 12-15)
Secondary outcomes (30)
Clinical variable: hirsutism
Presence of hirsutism as measured by the modified Ferriman \& Gallwey score
Measured: Every 3 months from study start to study completion (estimated 18 months)
Clinical variable: Acne
Presence of Acne as evaluated using the Leeds Acne Grading Scale
Measured: Every 3 months from study start to study completion (estimated 18 months)
Clinical variable: menstrual regularity
Assessment of the menstrual regularity
Measured: Every 3 months from study start to study completion (estimated 18 months)
Circulating androgens
Assessment by measurement of circulating androgens
Measured: Every 3 months from study start to study completion (estimated 18 months)
Lipids
Assessment by measurement of total cholesterol, low-density lipoprotein (LDL-cholesterol), high-density lipoprotein (HDL- cholesterol), triglycerides;
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Insulinaemia
Fasting and 2 hours after a 75-gr oral glucose load [oral glucose tolerance test (oGTT). Estimation of insulin resistance from fasting insulin and glucose levels using the homeostasis model assessment (HOMA);
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Inflammation markers
Inflammation markers
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Insulin sensitivity
Insulin sensitivity
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Ultra-sensitive C-reactive protein (us-CRP);
Ultra-sensitive C-reactive protein (us-CRP);
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Growth-and- differentiation factor-15 (GDF15);
Growth-and- differentiation factor-15 (GDF15);
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
High molecular weight adiponectin (HMW-adip),
High molecular weight adiponectin (HMW-adip),
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
C-X-C motif chemokine ligand 14 (CXCL14) (69,81);
C-X-C motif chemokine ligand 14 (CXCL14) (69,81);
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Epigenetic variable
Circulating microRNA 451-a (miR-451a) concentrations (88);
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Imaging: Cardiovascular risk
As measured by ultrasound
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Imaging: Body composition
As measured by dual-energy X-ray absorptiometry (DXA)
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Imaging: Abdominal fat distribution (subcutaneous and visceral)
As measured by MRI
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Imaging:hepatic fat
As measured by MRI
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Abdominal fat distribution
Waist circumference, Waist to hip ratio (WHR), and hepatic fat by MRI
Measured: Baseline and at the end of treatment (month 12) and 6 months after treatment
Weight
Weight measurement
Measured: Every 3 months from study start to study completion (estimated 18 months)
Improvement of co-morbidities
Improvement of co-morbidities
Measured: Every 3 months from study start to study completion (estimated 18 months)
Improvement of health behaviour
Improvement of health behaviour
Measured: Every 3 months from study start to study completion (estimated 18 months)
Improvement of health-related quality of life (HRQoL)
As reported by the patient
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Safety laboratory tests
Blood count, electrolyte panel, urea, alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyltransferase (GGT), creatinine, vitamin B12 and folic acid;
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Adverse events (AEs)
As reported by the patient
Measured: Every 3 months from study start to study completion (estimated 18 months)
Adherence
Adherence will be calculated as the ratio between the number of tablets prescribed and dispensed for the period between hospital appointments and the number of tablets returned by the patient at the following appointment;
Measured: Every 3 months from study start to study completion (estimated 18 months)
Acceptability of the treatment
Acceptability of the tablet by the study patients
Measured: Every 3 months from study start to study completion (estimated 18 months)
PROMs (patient-reported outcomes)
Questionnaire SF-36
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
PROMs (patient-reported outcomes)
Questionnaire PCOSQ
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
HRQoL (health-related quality of life)
Questionnaire SF-36
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
HRQoL (health-related quality of life)
Questionnaire PCOSQ
Measured: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2022
- Study start24 May 2022
- Primary completionApr 2025 (estimated)
- Study completionApr 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovary Syndrome (PCOS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase 2 clinical trial with four subgroups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 364 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundació Sant Joan de Déu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lourdes Ibañez, MD, PhD, Principal investigator, Investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05394142
- Sponsor's protocol ID
- SPIOMET4HEALTH
- Other IDs
- 2021-003177-58
- Acronym
- SPIOMET4HEALTH
- Status last verified
- Apr 2024
- First submitted
- 9 May 2022
- Last updated
- 22 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05394142
- Acronym / sponsor ID
- SPIOMET4HEALTH / SPIOMET4HEALTH
- Conditions
- Polycystic Ovary Syndrome (PCOS)
- Keywords
- polycystic ovary syndrome, spironolactone, pioglitazone, metformin, peadiatric, PCOS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 364 participants (estimated)
- Lead sponsor
- Fundació Sant Joan de DéuUniversity, hospital or other
- Study start
- 24 May 2022 (actual)
- Primary completion
- Apr 2025 (estimated)
- Study completion
- Apr 2025 (estimated)
- First posted
- 27 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women with polycystic ovary syndrome.
Study description: Currently, there is no European Medicines Agency /U.S. Food and Drug Administration (FDA)-approved therapy for polycystic ovary syndrome in adolescent girls and young adult women. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of AYAs with PCOS, including those without pregnancy risk. OCs alleviate key symptoms by inducing a pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin (SHBG), but OCs do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility and possibly, for lifelong co-morbidities.
Given the key role of hepato-visceral fat excess in the pathogenesis of PCOS, the prime aim of the treatment should be to achieve a preferential loss of central fat, which should in turn normalise the entire PCOS phenotype. Recent evidence disclosed that a treatment consisting of a fixed low-dose combination of two insulin sensitisers [pioglitazone (PIO) and metformin (MET), with different modes of action], and one mixed anti-androgen and anti-mineralocorticoid (spironolactone), was superior to an OC in normalising the PCOS phenotype, including ovulation rates and hepato-visceral fat.
The study's main goals are to assess the efficacy, tolerability and safety of a new treatment (SPIOMET) for adolescent girls and young adult women with polycistic ovarian syndrome; the comparison (in this order) of each SPIOMET, spironolactone and pioglitazone (SPIO) and PIO over placebo; and in addition, the comparison of SPIOMET over PIO and over SPIO (in this order).
Primary Objective: To test the efficacy of SPIOMET in normalising ovulation rate in adolescents and young adult women with PCOS.
Secondary Objectives: To test the efficacy of SPIOMET in normalising the endocrine-metabolic status, to describe the drug safety profile and to assess the adherence and subjective acceptability, as well as the quality of life of the participating subjects.
Detailed description
This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase II clinical trial to evaluate the efficacy, tolerability, and safety of a fixed dose combination of Spironolactone, Pioglitazone and Metformin (SPIOMET) for adolescent girls and young adult women (AYAs) with polycystic ovary syndrome (PCOS).
Study description: Currently, there is no European Medicines Agency (EMA)/U.S. Food and Drug Administration (FDA)-approved therapy for PCOS in AYAs. Oral contraceptives (OCs) are prescribed off-label to approximately 98% of AYAs with PCOS, including those without pregnancy risk. OCs alleviate key symptoms by inducing a pharmacological combination of anovulatory subfertility, regular pseudo-menses, and extreme elevations of sex hormone-binding globulin (SHBG), but OCs do not revert the underlying pathophysiology, and patients remain at risk for post-treatment subfertility and possibly, for lifelong co-morbidities.
Given the key role of hepato-visceral fat excess in the pathogenesis of PCOS, the prime aim of the treatment should be to achieve a preferential loss of central fat, which should in turn normalise the entire PCOS phenotype. Recent evidence disclosed that a treatment consisting of a fixed low-dose combination of two insulin sensitisers [pioglitazone (PIO) and metformin (MET), with different modes of action], and one mixed anti-androgen and anti-mineralocorticoid (spironolactone), was superior to an OC in normalising the PCOS phenotype, including ovulation rates and hepato-visceral fat.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- This is a multi-centre, multi-national, double-blinded, placebo-controlled, parallel, randomised Phase 2 clinical trial with four subgroups
| Arm | Type | Receives |
|---|---|---|
| Arm 1 - Placebo | Placebo comparator | Drug: PlaceboPlacebo |
| Arm 1 - PIO | Experimental | Drug: PioglitazonePioglitazone |
| Arm 1 - SPIO | Experimental | Drug: Pioglitazone, Drug: SpironolactoneSpironolactone and Pioglitazone |
| Arm 1 - SPIOMET | Experimental | Drug: Pioglitazone, Drug: Spironolactone, Drug: MetforminSpironolactone, Pioglitazone and Metformin |
Who may qualify
- Ages
- 12 to 23 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- 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;
- Gynaecological age of 2 years or more;
- 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);
- 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);
- 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;
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboComparator arm with placebo | Drug | Arm 1 - Placebo |
| PioglitazoneAlso: PIOPioglitazone 7.5 mg/day | Drug | Arm 1 - PIO, Arm 1 - SPIO, Arm 1 - SPIOMET |
| SpironolactoneAlso: SSpironolactone 50 mg/day | Drug | Arm 1 - SPIO, Arm 1 - SPIOMET |
| MetforminAlso: METMetformin 850 mg/day | Drug | Arm 1 - SPIOMET |
Primary outcome
On-treatment ovulation rate.
Time frame: Following end of each two 12-week on-treatment periods (month 0-3 and month 9-12)
On-treatment ovulation rate.
Post-treatment ovulation rate.
Time frame: Following the end of post-treatment period (month 12-15)
Post-treatment ovulation rate.
30 secondary outcomes
Clinical variable: hirsutism
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Clinical variable: Acne
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Clinical variable: menstrual regularity
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Circulating androgens
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Lipids
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Insulinaemia
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Inflammation markers
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Insulin sensitivity
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Ultra-sensitive C-reactive protein (us-CRP);
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Growth-and- differentiation factor-15 (GDF15);
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
High molecular weight adiponectin (HMW-adip),
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
C-X-C motif chemokine ligand 14 (CXCL14) (69,81);
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Epigenetic variable
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Imaging: Cardiovascular risk
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Imaging: Body composition
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Imaging: Abdominal fat distribution (subcutaneous and visceral)
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Imaging:hepatic fat
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Abdominal fat distribution
Time frame: Baseline and at the end of treatment (month 12) and 6 months after treatment
Weight
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Improvement of co-morbidities
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Improvement of health behaviour
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Improvement of health-related quality of life (HRQoL)
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Safety laboratory tests
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Adverse events (AEs)
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Adherence
Time frame: Every 3 months from study start to study completion (estimated 18 months)
Acceptability of the treatment
Time frame: Every 3 months from study start to study completion (estimated 18 months)
PROMs (patient-reported outcomes)
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
PROMs (patient-reported outcomes)
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
HRQoL (health-related quality of life)
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
HRQoL (health-related quality of life)
Time frame: Baseline, at month 3, month 6 and month 12 whiled on treatment and 6 months after the end of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2024.
- Individual participant dataSharing planned: No
Related trials for Polycystic Ovary Syndrome (PCOS)
Recruiting
Efficacy of Ovarian Drilling Via vNOTES Laparoscopy in Patients With PCOS
PCOS (Polycystic Ovary Syndrome)
RecruitingPhase 1
Efficacy of Injectable Vitamin D Supplementation in Females With Polycystic Ovary Syndrome
Anovulatory Infertility
RecruitingObservational study
The Value of LC-MS/MS Detection of Androgen Profiles in the Diagnosis of PCOS: A Prospective, Multicenter Real-world Study
Polycystic Ovary Syndrome (PCOS)
Recruiting
The Effects of the Mediterranean Diet and Synbiotics in Polycystic Ovary Syndrome
PCOS (Polycystic Ovary Syndrome)
Recruiting
Brown Adipose Tissue Modulation in Polycystic Ovary Syndrome Using Infrared Thermography
Polycystic Ovary Syndrome (PCOS)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elizabeth García Pérez, PhD contact
Lourdes Ibañez, MD, PhD principal investigator
Investigator
7 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pioglitazone, Spironolactone and Metformin in people with Polycystic Ovary Syndrome (PCOS), run by Fundació Sant Joan de Déu at 7 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Spain, Austria, Denmark, Italy, Norway and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Rita Malpique, PhD (+34936 00 97 51 ext. 77806, rita.malpique@sjd.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
On-treatment ovulation rate. (time frame: Following end of each two 12-week on-treatment periods (month 0-3 and month 9-12)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Apr 2024; AzTrials last refreshed its copy on 7 Nov 2026.