Condition category
Nutritional, Metabolic, Endocrine
Date applied
15/01/2010
Date assigned
06/04/2010
Last edited
08/07/2013
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof Lourdes Ibáñez

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

PI09/90444

Study information

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

Acronym

DIO

Study hypothesis

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

CEIC Fundacio Sant Joan de Déu approved on the 7th of October 2009

Study design

Randomised 2 arm open-labeled active controlled parallel group trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Prevention

Patient information sheet

Not available in web format, please use contact details below to request a patient information sheet.

Condition

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 names

Ethynil-estradiol cyproterone acetate, metformin-flutamide-pioglitazone

Primary outcome measures

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

Secondary outcome measures

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

Overall trial start date

01/02/2010

Overall trial end date

05/11/2011

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Child

Gender

Female

Target number of participants

46

Participant 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

Recruitment start date

01/02/2010

Recruitment end date

05/11/2011

Locations

Countries of recruitment

Spain

Trial participating centre

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

Sponsor information

Organisation

Hospital Sant Joan de Déu (Spain)

Sponsor details

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

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Hospital/treatment centre

Funder name

Instituto de Salud Carlos III (Spain) (ref: PI09/90444)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2011 results in http://www.ncbi.nlm.nih.gov/pubmed/21865363
2. 2012 results in http://www.ncbi.nlm.nih.gov/pubmed/22791755
3. 2013 results in http://www.ncbi.nlm.nih.gov/pubmed/23547047

Publication citations

  1. Results

    Ibáñez L, Diaz M, Sebastiani G, Sánchez-Infantes D, Salvador C, Lopez-Bermejo A, de Zegher F, Treatment of androgen excess in adolescent girls: ethinylestradiol-cyproteroneacetate versus low-dose pioglitazone-flutamide-metformin., J. Clin. Endocrinol. Metab., 2011, 96, 11, 3361-3366, doi: 10.1210/jc.2011-1671.

  2. Results

    Díaz M, Chacón MR, López-Bermejo A, Maymó-Masip E, Salvador C, Vendrell J, de Zegher F, Ibáñez L, Ethinyl estradiol-cyproterone acetate versus low-dose pioglitazone-flutamide-metformin for adolescent girls with androgen excess: divergent effects on CD163, TWEAK receptor, ANGPTL4, and LEPTIN expression in subcutaneous adipose tissue., J. Clin. Endocrinol. Metab., 2012, 97, 10, 3630-3638, doi: 10.1210/jc.2012-1754.

  3. Results

    Ibáñez L, Díaz M, Sebastiani G, Marcos MV, López-Bermejo A, de Zegher F, Oral contraception vs insulin sensitization for 18 months in nonobese adolescents with androgen excess: posttreatment differences in C-reactive protein, intima-media thickness, visceral adiposity, insulin sensitivity, and menstrual regularity., J. Clin. Endocrinol. Metab., 2013, 98, 5, E902-7, doi: 10.1210/jc.2013-1041.

Additional files

Editorial Notes