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Register:	ISRCTN
Last refreshed on:	29 August 2022
Main ID:	ISRCTN11062950
Date of registration:	21/09/2015
Prospective Registration:	Yes
Primary sponsor:	Hospital Sant Joan de Deu, University of Barcelona
Public title:	Comparison of the effects of an oral contraceptive with those of a combined therapy with insulin sensitizers and anti-androgens in young girls with ovarian androgen excess and without pregnancy risk, on markers of cardiometabolic health
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
Date of first enrolment:	10/12/2015
Target sample size:	40
Recruitment status:	Completed
URL:	https://www.isrctn.com/ISRCTN11062950
Study type:	Interventional
Study design:	Interventional, single-centre study (Treatment)
Phase:	Phase III

Countries of recruitment
Spain

Contacts

Name:	Lourdes Ibañez
Address:	Hospital Sant Joan de Déu University of Barcelona 08950 Esplugues Spain
Telephone:
Email:
Affiliation:

Name:
Address:
Telephone:
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Affiliation:

Key inclusion & exclusion criteria

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

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

Age minimum:
Age maximum:
Gender: Female

Health Condition(s) or Problem(s) studied

Hyperinsulinemic androgen excess in adolescent girls
Nutritional, Metabolic, Endocrine
Androgen excess

Intervention(s)

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).

Primary Outcome(s)

Current primary outcome measures as of 14/09/2018:
1. Insulinemia assessed by immunochemiluminescence every 6 months while on treatment and 6 months after end of treatment
2. Visceral and hepatic fat assessed by MRI every 6 months while on treatment and 6 months after end of treatment
Post-treatment endpoints:
3. Ovulation rates assessed by ELISA of weekly salivary progesterone during the second and fourth quarter of the follow-up year

Previous 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(s)

Current secondary outcome measures as of 17/09/2018:
On-treatment endpoints:
1. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence), and AMH (ELISA) at baseline and after 12 months on treatment.
2. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at baseline and after 12 months of treatment.

Post-treatment endpoints:
3. Measures of androgen excess: hirsutism (Ferriman & Gallwey score); acne (Leeds score); testosterone (immunochemiluminescence) and AMH (ELISA) after 6 and 12 months off treatment.
4. Measurements of cardio-metabolic risk: C-reactive protein (Architect c8000; Abbott); HMW adiponectin (ELISA), carotid intima-media thickness (ultrasound); insulinemia (Immunochemiluminiscence); visceral and hepatic fat (MRI); HMW adiponectin (ELISA), S100A4 (ELISA), at 6 and 12 months off treatment.

Previous secondary outcome measures as of 13/09/2018:
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
7. Serum S100A4 on treatment
8. Anti-Mullerian hormone (AMH) at baseline and after 12 months on treatment

Previous 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)

Secondary ID(s)

PI15/01078

2015-005092-24

Source(s) of Monetary Support

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

Secondary Sponsor(s)

Ethics review

Status:
Approval date:
Contact:

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

Results

Results available:	Yes
Date Posted:
Date Completed:	20/09/2019
URL:

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