Comparison of two therapies for hyperandrogenism in girls

ISRCTN	ISRCTN45546616
DOI	https://doi.org/10.1186/ISRCTN45546616
Protocol serial number	PI09/90444
Sponsor	Hospital Sant Joan de Déu (Spain)
Funder	Instituto de Salud Carlos III (Spain) (ref: PI09/90444)

Submission date: 15/01/2010
Registration date: 06/04/2010
Last edited: 08/07/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Lourdes Ibáñez
Scientific

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

Study information

Primary study design	Interventional
Study design	Randomised 2 arm open-labeled active controlled parallel group trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Ethynil-estradiol cyproterone acetate versus low-dose metformin-flutamide-pioglitazone in girls with hyperinsulinemic androgen excess: effects on parameters of chronic inflammation, and on risk factors for type 2 diabetes and cardiovascular disease
Study acronym	DIO
Study objectives	Low-dose metformin-flutamide-pioglitazone will prove to be superior to ethynil-estradiol-cyproterone acetate in improving chronic inflammation and risk factors for type 2 diabetes and cardiovascular disease Please note that as of 08/02/2011 the study has been updated. The study design of this trial has changed from a "Randomised 2 arm double blind active controlled parallel group trial" to a "Randomised 2 arm open-labeled active controlled parallel group trial".
Ethics approval(s)	CEIC Fundacio Sant Joan de Déu approved on the 7th of October 2009
Health condition(s) or problem(s) studied	Hyperinsulinemic ovarian androgen excess
Intervention	Current interventions as of 08/02/2011: Adolescents with androgen excess will be allocated to treatment with metformin-flutamide-pioglitazone or ethynil-estradiol-cyproterone acetate over 18 months. Auxology, blood counts, liver and renal functions, endocrine-metabolic parameters (fasting blood) and body composition will be measured at 0 and 18 mo and at 6 mo after treatment stop Previous interventions: Adolescents with androgen excess will be allocated to treatment with metformin-flutamide-pioglitazone or ethynil-estradiol-cyproterone acetate over 12 months. Auxology, blood counts, liver and renal functions, endocrine-metabolic parameters (fasting blood) and body composition will be measured at 0 and 12 mo and at 6 mo after treatment stop.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Ethynil-estradiol cyproterone acetate, metformin-flutamide-pioglitazone
Primary outcome measure(s)	1. Insulin sensitivity measured by Homeostasis Model Assessment (HOMA) 2. Insulin 3. Abdominal fat measured by Dual Energy X-Ray Absorptiometry (DXA) 4. Abdominal visceral fat and intrahepatic lipid content 5. Intermuscular Adipose Tissue (IMAT) measured by Magnetic Resonance (MR) 6. Carotid intima media thickness (IMT) measured by Doppler sonography
Key secondary outcome measure(s)	1. Hirsutism measured by Ferriman & Gallwey score 2. Androgens 3. Triglycerides 4. Ultrasensitive C-reactive protein 5. Neutrophile/lymphocyte ratio 6. High molecular weight adiponectin 7. Changes in the size, number, and distribution of adipocytes determined by subcutaneous adipose tissue biopsy
Completion date	05/11/2011

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	14 Years
Upper age limit	17 Years
Sex	Female
Target sample size at registration	46
Key inclusion criteria	1. Adolescent girls (14-17 yr) 2. Two or more yr beyond menarche 3. BMI less than the 97th centile for age 4. Clinical and biochemical signs of androgen excess (hirsutism [Ferriman & Gallwey score >8] and/or acne and/or menstrual irregularities) 5. Total testosterone >60 ng/dL and/or free androgen index >5 6. Hyperinsulinism: fasting insulin >15 uU/mL; glucose/insulin ratio <7, or peak insulin after an OGTT >100 uU/mL
Key exclusion criteria	1. Pregnancy or pregnancy risk 2. Late-onset congenital adrenal hyperplasia due to 21-OH deficiency 3. Hyperprolactinemia 4. Cushing's syndrome 5. Hypothyroidism 6. Abnormal liver or kidney function, Creatine Phosphokinase (CPK) or Lactate Dehydrogenase (LDH) 6. Diabetes or impaired glucose tolerance 7. Cutaneous allergies 8. Treatment with anti-androgens, estroprogestagens, or medications interfering with lipid and carbohydrate metabolism during the previous 6 mo 9. Bacterial infections 10. Inflammatory intestinal conditions
Date of first enrolment	01/02/2010
Date of final enrolment	05/11/2011

Locations

Countries of recruitment

Spain

Study participating centre

Hospital Sant Joan de Déu, University of Barcelona

Esplugues, Barcelona
08950
Spain

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/11/2011		Yes	No
Results article	results	01/10/2012		Yes	No
Results article	results	01/05/2013		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes