NCT00948402

Brief Summary

Insulin-resistance plays an important role in polycystic ovary syndrome (PCOS) physiopathology. The phosphoprotein enriched in the diabetes (PED/PEA-15), a 15 kDa protein related to insulin sensitivity, is over-expressed in type 2 diabetic patients and in PCOS women, independently of obesity. The effectiveness of oral contraceptives pills (OCP) or metformin (MET) in PCOS management is still uncertain. Aim of this pilot clinical study was to compare the effects of OCPs or MET on the expression of PED/PEA-15 in association with insulin sensitivity in obese PCOS women. Outcome measures: PED/PEA-15, BMI, plasma glucose and insulin, 1/HOMA-IR, homeostasis model assessment of insulin resistance; QUICKI, quantitative insulin sensitivity check index; ISI: whole-body insulin sensitivity index. Study design: twenty obese PCOS women (age: 24.7±18 yr; BMI: 30±2.4 kg/m2) were randomized according to insulin sensitivity to receive 30 µg ethinylestradiol plus 30 mg drospirenone 21 day/month or MET 1250 mg three times daily for 6 months. Results: At baseline, age and BMI were not different in the two groups; PED/PEA-15 protein expression was higher in MET than in OCP group (p=0.011), along with higher 1/HOMA-IR (p=0.004), and lower QUICKI and ISI (p=0.003 and p\<0.001, respectively). After treatment, independently of body weight, only in MET group PED/PEA-15 decreased (p=0.004), along with insulin and 1/HOMA-IR (p\<0.001), and QUICKI and ISI increased (p\<0.001). Insulin sensitivity indexes improvement correlated significantly with PED/PEA-15 protein expression, but not with BMI. Conclusions: PED/PEA-15 protein over-expression in obese PCOS women with IR reduced after a six month treatment with MET, while remained unchanged in the OCP group. The reduction was independent of body weight, and correlated with insulin sensitivity indexes. This effect further supported MET as a more effective therapy than OCPs for obese PCOS women with IR, also when fertility is not required.

Trial Health

100
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_3

Timeline
Completed

Started Dec 2006

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2006

Completed
Same day until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2006

Completed
2.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2009

Completed
7 months until next milestone

First Submitted

Initial submission to the registry

July 24, 2009

Completed
5 days until next milestone

First Posted

Study publicly available on registry

July 29, 2009

Completed
Last Updated

October 14, 2009

Status Verified

October 1, 2009

Enrollment Period

Same day

First QC Date

July 24, 2009

Last Update Submit

October 13, 2009

Conditions

Keywords

PED/PEA-15 proteinPCOSIRmetforminOCPOral Contraceptive

Outcome Measures

Primary Outcomes (1)

  • PED/PEA-15 protein expression

    6 months

Secondary Outcomes (1)

  • BMI, plasma glucose, plasma insulin, insulin sensitivity indexes (1/HOMA-IR, homeostasis model assessment of insulin resistance; QUICKI, quantitative insulin sensitivity check index; ISI, whole-body insulin sensitivity index).

    6 months

Study Arms (2)

metformin

EXPERIMENTAL
Drug: Metformin

oral contraceptive

ACTIVE COMPARATOR
Drug: oral contraceptive

Interventions

metformin 1250 mg three times daily

Also known as: Biguanides
metformin

30 µg ethinylestradiol plus 30 mg drospirenone 21 day/month.

Also known as: estroprogestins
oral contraceptive

Eligibility Criteria

Age21 Years - 28 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • female
  • premenopausal
  • obesity
  • PCOS.

You may not qualify if:

  • pregnancy
  • type 2 diabetes or impaired glucose tolerance
  • hypothyroidism
  • hyperprolactinaemia
  • Cushing's syndrome
  • nonclassical congenital adrenal hyperplasia
  • previous (within the last 6 months) use of oral contraceptives
  • glucocorticoids
  • antiandrogens
  • ovulation induction agents
  • antidiabetic and antiobesity drugs, or other hormonal drugs.
  • None of the subjects was affected by any neoplastic, metabolic, hepatic, and cardiovascular disorder or other concurrent medical illness (i.e. diabetes, renal disease, and malabsorptive disorders),acute and chronic inflammations based on medical history, physical examination, and routine laboratory tests, including measurement of oral temperature, white blood cell count and urinalysis.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Related Publications (2)

  • Savastano S, Di Somma C, Pizza G, De Rosa A, Nedi V, Rossi A, Orio F, Lombardi G, Colao A, Tarantino G. Liver-spleen axis, insulin-like growth factor-(IGF)-I axis and fat mass in overweight/obese females. J Transl Med. 2011 Aug 16;9:136. doi: 10.1186/1479-5876-9-136.

  • Savastano S, Valentino R, Pizza G, De Rosa A, Orio F, Passaretti F, Formisano P, Lombardi G, Beguinot F, Colao A. Preliminary data on effects of metformin on PED/PEA-15 cellular levels in obese women with polycystic ovary syndrome. J Endocrinol Invest. 2010 Jul-Aug;33(7):446-50. doi: 10.1007/BF03346622.

MeSH Terms

Conditions

Polycystic Ovary SyndromeInsulin Resistance

Interventions

MetforminBiguanidesContraceptives, Oral

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System DiseasesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

GuanidinesAmidinesOrganic ChemicalsContraceptive Agents, FemaleContraceptive AgentsReproductive Control AgentsPhysiological Effects of DrugsPharmacologic ActionsChemical Actions and UsesTherapeutic Uses

Study Officials

  • Annamaria Colao, MD PhD

    Department of Molecular and Clinical Endocrinology and Oncology Federico II University of Naples

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

July 24, 2009

First Posted

July 29, 2009

Study Start

December 1, 2006

Primary Completion

December 1, 2006

Study Completion

January 1, 2009

Last Updated

October 14, 2009

Record last verified: 2009-10