Condition category
Nutritional, Metabolic, Endocrine
Date applied
16/09/2015
Date assigned
21/09/2015
Last edited
24/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Polycystic ovary syndrome (PCOS) is a medical condition that affects the function of a woman’s ovaries. Women with PCOS may have cysts in the ovaries, irregular ovulation and high levels of androgens (male hormones). Symptoms include irregular periods (or no periods at all), difficulties getting pregnant, excessive hair (hirsutism), commonly on the face, chest, back and buttocks, gaining weight, hair thinning and acne. It is also associated with an increased risk of type 2 diabetes and other health problems later in life, such as cardiovascular disease. There is no approved therapy. Prime recommendation is to give an oral contraceptive (OC) which treats the symptoms, but may decrease the sensitivity to insulin, worsen markers of cardiovascular health, and therefore affect the long-term health. Here, we compare the long-term effects of an OC with those of a low-dose combination of medications that improve insulin sensitivity and decrease the affects of androgen to investigate whether besides the clinical symptoms, this combination is capable of improving the risks for future complications for young women with PCOS.

Who can participate?
Girls under 16 diagnosed with PCOS with decreased sensitivity to insulin, excess androgen levels and with no/irregular periods.

What does the study involve?
Participants are randomly allocated to one of two groups. Those in group 1 are given Loette Diario (OC). Those in group 2 are given SPIOMET, that is, spironolactone, pioglitazone and metformin; this combination aims to improve insulin sensitivity and reduce the effects of androgen. All participants are tested for insulinema (insulin in the blood) and their levels of visceral (abdominal) and hepatic (liver) fat.

What are the possible benefits and risks of participating?
This study compares the standard treatment with an alternative, pathophysiology-based therapy (with a low-dose combination of insulin sensitizers and anti-androgens). A preliminary study has been performed using the combinations to be used here and the results show a divergence in the outcomes, with the combination having more benefits on risk markers. The medications are safe and there is no evidence of side effects.

Where is the study run from?
Hospital Sant Joan de Déu, University of Barcelona (Spain)

When is the study starting and how long is it expected to run for?
December 2015 to December 2018

Who is funding the study?
Ministry of Science and Innovation, Institute of Health Carlos III (Spain)

Who is the main contact?
Professor Lourdes Ibañez

Trial website

Contact information

Type

Scientific

Primary contact

Prof Lourdes Ibañez

ORCID ID

http://orcid.org/0000-0003-4595-7191

Contact details

Hospital Sant Joan de Déu
University of Barcelona
Esplugues
08950
Spain

Additional identifiers

EudraCT number

2015-005092-24

ClinicalTrials.gov number

Protocol/serial number

PI15/01078

Study information

Scientific title

Ethinylestradiol-levonorgestrel versus spironolactone-pioglitazone-metformin (SPIOMET)
for adolescent girls with hyperinsulinemic androgen excess: effects on hepatic and visceral fat and on insulin sensitivity

Acronym

OC vs SPIOMET

Study hypothesis

Oral contraceptives (OC) and SPIOMET will improve the measures of androgen excess comparably. SPIOMET treatment will be followed by more favorable changes of the primary outcomes (visceral and hepatic fat and insulinemia), and of secondary outcomes (lipids, CRP, carotic intima-media thickness [cIMT], high-molecular-weight adiponectin, miRNAs, leukocyte telomere length, microbiome, gene expression in subcutaneous adipose tissue).

Ethics approval

Agencia Española del Medicamento y Productos Sanitarios, 22/01/2016

Study design

Interventional, single-centre study

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a participant information sheet

Condition

Hyperinsulinemic androgen excess in adolescent girls

Intervention

In this single-centre, open-labelled, controlled trial, the randomization (1:1) will be web-based (http://www.SealedEnvelope.com), using random permuted blocks, with strata for age (<16.0 or ≥16.0 years) and BMI (<24.0 or ≥24.0 Kg/m2).

Girls will be randomly assigned to receive once daily, at dinner time, either Loette Diario (Pfizer, Madrid, Spain; 20 mcg ethinylestradiol plus 100 mg levonorgestrel for 21/28 days, and placebo for 7/28 days) or SPIOMET, a low-dose combination of separate generics: 50 mg spironolactone (one half of a 100 mg tablet of Aldactone from Pfizer, Madrid, Spain); 7.5 mg pioglitazone (one half of a 15 mg tablet of Actos from Takeda, Madrid, Spain); and 850 mg metformin (one full 850 mg tablet of Metformina from Sandoz, Barcelona, Spain).

The randomization will be performed by an investigator who will not be based in the recruiting hospital and who will be blinded to the patients’ characteristics (except for age and BMI).

Intervention type

Drug

Phase

Phase III

Drug names

1. Loette Diario (Pfizer, Madrid, Spain; 20 mcg ethinylestradiol plus 100 mg levonorgestrel)
2. Spironolactone ( 100 mg tablets of Aldactone, Pfizer, Madrid, Spain)
3. Pioglitazone (15 mg tablet of Actos, Takeda, Madrid, Spain)
4. Metformin (850 mg tablet of Metformina, Sandoz, Barcelona, Spain)

Primary outcome measures

As of 07/03/2016:
On-treatment endpoints:
1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence
2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment
Post-treatment endpoints:
3. Ovulation rates

Previous primary outcome measures:
1. Insulinemia: on treatment every 6 months; 6 months off treatment. Method: immunoquimioluminescence
2. Visceral & hepatic fat: MRI. on treatment every 6 months; 6 months off treatment

Secondary outcome measures

As of 07/03/2016:
On-treatment endpoints:
1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence)
2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound)
Post-treatment endpoints:
3. Insulinemia
4. Visceral & hepatic fat
5. Measures of androgen excess
6. C-reactive protein, HMW adiponectin, carotid intima-media thickness

Previous secondary outcome measures:
1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence)
2. C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound)


Overall trial start date

02/12/2015

Overall trial end date

30/12/2018

Reason abandoned

Eligibility

Participant inclusion criteria

1. Hyperinsulinemia, defined as fasting insulinemia >15 IU/mL and/or a peak insulinemia >150 IU/mL and/or mean insulinemia >84 IU/mL on a 2-hour oral glucose tolerance test (oGTT)
2. Presence of both clinical and endocrine androgen excess, as defined by hirsutism score >8 (Ferriman-Gallwey scale), amenorrhea (no menses for more than 3 months) or oligomenorrhea (menstrual intervals >45 days), and high circulating concentrations of testosterone in the follicular phase (cycle day 3-7) or after 2 months of amenorrhea

Participant type

Patient

Age group

Child

Gender

Female

Target number of participants

40

Participant exclusion criteria

1. Pregnancy risk (throughout the study)
2. Anemia or bleeding disorder
3. Evidence of thyroid, liver or kidney dysfunction; abnormal electrolytes
4. Hyperprolactinemia
5. 21-hydroxylase deficiency (17-hydroxyprogesterone levels ≥ 200 ng/dL in the follicular phase or after two months of amenorrhea)
6. Glucose intolerance or diabetes mellitus
7. Use of medication affecting gonadal or adrenal function, or carbohydrate or lipid metabolism

Recruitment start date

10/12/2015

Recruitment end date

10/12/2016

Locations

Countries of recruitment

Spain

Trial participating centre

Hospital Sant Joan de Déu, University of Barcelona
Passeig de Sant Joan de Déu, 2
Esplugues
08950
Spain

Sponsor information

Organisation

Hospital Sant Joan de Deu, University of Barcelona

Sponsor details

Passeig de Sant Joan de Déu
2
Esplugues
08950
Spain
+34 93 2804000
aode@fsjd.org

Sponsor type

University/education

Website

www.hsjdbcn.org

Funders

Funder type

Not defined

Funder name

Ministry of Science and Innovation, Institute of Health Carlos III (Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III) (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Our aim is to publish together the on-treatment and off-treatment results after completion of the protocol.
Should any of the novel variables result in outstanding and/or unexpected results, we may chose to publish those results separately.

Intention to publish date

30/01/2017

Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

24/03/2016: Ethics approval information added. 18/03/2016: Internal review 07/03/2016: Updated primary and secondary outcome measures. Details of changes are in appropriate fields.