Phlebotomy and Polycystic Ovary Syndrome

July 25, 2022 updated by: Manuel Luque Ramírez

Effect of Decreasing Iron Tissue Depots on the Cardiovascular Risk of Women With Polycystic Ovary Syndrome

AIMS To study the effects of the decrease in iron tissue depots after scheduled bloodletting on insulin sensitivity, carbohydrate metabolism, classic and non-classic cardiovascular risk factors in patients with functional hyperandrogenism (polycystic ovary syndrome & idiopathic hyperandrogenism) on standard treatment with combined oral contraceptives (COC) according to usual clinical practice.

METHODOLOGY

Open label, controlled, parallel, prospective study of 12 months of duration, with 2 randomized arms of follow-up:

i) Intervention Group: Patients with functional hyperandrogenism on standard COC treatment randomly allocated to perform scheduled phlebotomies from the third month of treatment to the end of the study (3 times with a 3-month interval between them).

ii) Control Group: Patients with functional hyperandrogenism on standard COC treatment randomly allocated to follow-up without bloodletting.

The whole group of patients will undergo a comprehensive anthropometric and hormonal assessment, evaluation of classic cardiovascular risk factors (insulin sensitivity and carbohydrate metabolism after a standard oral glucose test- 75 g), lipid profile, ambulatory and office blood pressure monitoring, proinflammatory profile, oxidative stress status, autonomic function assessment, and iron-related metabolism parameters at baseline, after 3-month COC treatment and after reduction of iron tissue depots plus OC in the Intervention Group of patients, and throughout follow-up under treatment with COC in the Control Group of patients. If a significant relationship between circulating hepcidin levels and elevated ferritin concentrations is observed, a study of the potential influence of mutations/polymorphic variants of hepcidin gene on ferritin values will be performed as well.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

37

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Madrid, Spain, 28034
        • Diabetes, Obesity and Human Reproduction Research Group, Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Universidad de Alcalá, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 43 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Premenopausal women with functional hyperandrogenism defined as:

    • Polycystic ovary syndrome (PCOS): Clinical and biochemical hyperandrogenism plus ovulatory dysfunction or polycystic ovarian morphology.
    • Idiopathic hyperandrogenism: Clinical and biochemical hyperandrogenism with normal ovulatory cycles and normal ovarian morphology.
  2. Combined oral contraceptive pill indication for treatment: i) hyperandrogenism-related dermo-cosmetic complaints with psychoemotional impact; ii) endometrial protection; and/or iii) contraception desire.
  3. Scheduled phlebotomy acceptation if randomly allocated.
  4. Signed informed consent.

Exclusion Criteria:

  1. Contraindication for blood donation.
  2. Plasma ferritin < 76 pmol/l and/or transferrin saturation percent < 15%.
  3. Anemia (plasma hemoglobin < 12 g/dl or hematocrit < 36%).
  4. Chronic kidney disease (eGFR < 60 ml/min per 1.73 m2).
  5. Personal history of dyslipidemia, hypertension, prediabetes, diabetes mellitus, gestational diabetes or cardiovascular events.
  6. Treatment with oral contraceptives, antiandrogens, insulin sensitizers, drugs that might interfere with blood pressure regulation, lipid profile or carbohydrate metabolism, and oral/parenteral iron therapy for the previous 3 months to inclusion.
  7. Previous surgical treatment for PCOS.
  8. History of blood donation for the previous 12 months to inclusion.
  9. Current history of infectious disease, inflammatory disease, liver disease, neurologic disease or malignancy.
  10. Eating disorders. Body mass index < 18.5 Kg/m2.
  11. Hereditary hemochromatosis.
  12. Celiac disease or malabsorptive disorder.
  13. Contraindication for treatment with combined oral contraceptives.
  14. Pregnancy.
  15. Current smoking, recreational drug use or excessive alcohol consumption (> 40 g per day).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Intervention
Premenopausal women with functional hyperandrogenism under combined oral contraceptive pill qd as usual clinical practice who will undergo a scheduled standard phlebotomy every 3 months from month 3 to 12 of follow-up.
Procedure: Phlebotomy
Scheduled standard phlebotomy every three months from month 3 to 12 of follow-up.
Other Names:
  • Bloodletting
  • Blood donation
Drug: ethinylestradiol
35 mcg ethinylestradiol qd for 21 days per month as usual clinical practice.
Drug: Cyproterone Acetate
2 mg cyproterone acetate qd for 21 days per month as usual clinical practice.
Active Comparator: Control
Premenopausal women with functional hyperandrogenism under standard combined oral contraceptive pill qd as usual clinical practice.
Drug: ethinylestradiol
35 mcg ethinylestradiol qd for 21 days per month as usual clinical practice.
Drug: Cyproterone Acetate
2 mg cyproterone acetate qd for 21 days per month as usual clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in the Matsuda index from the circulating glucose and insulin concentrations during and standard oral glucose tolerance test.
Time Frame: one year
one year
Percentage of patients with Hb < 12 g/dl or hematocrit <36% throughout the study
Time Frame: one year
one year

Secondary Outcome Measures

Outcome Measure
Time Frame
Change in the percentage of patients with undiagnosed prediabetes/diabetes between month 0 and 12 of follow-up
Time Frame: one year
one year
Change in the Disposition index between month 0 and 12 of follow-up
Time Frame: one year
one year
Change in the lipid profile between month 0 and 12 of follow-up
Time Frame: one year
one year
Changes in the blood pressure recordings between month 0 and 12 of follow-up
Time Frame: one year
one year
Percentage of patients with ferropenia throughout the study
Time Frame: one year
one year
Percentage of patients with a hypovolemic event during blood donation
Time Frame: one year
one year

Other Outcome Measures

Outcome Measure
Time Frame
Subclinical chronic inflammation
Time Frame: one year
one year
Oxidative stress
Time Frame: one year
one year
Autonomic vascular function
Time Frame: one year
one year
Blood clotting test
Time Frame: one year
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Manuel Luque Ramírez

Collaborators

Instituto de Salud Carlos III

Investigators

  • Principal Investigator: Manuel Luque Ramírez, M.D., Ph.D., Assistant in Endocrinology. Member of the Diabetes, Obesity and Human Reproduction Research Group from the lnstituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2015

Primary Completion (Actual)

June 1, 2020

Study Completion (Actual)

June 1, 2020

Study Registration Dates

First Submitted

May 27, 2015

First Submitted That Met QC Criteria

June 1, 2015

First Posted (Estimate)

June 2, 2015

Study Record Updates

Last Update Posted (Actual)

July 27, 2022

Last Update Submitted That Met QC Criteria

July 25, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PI14/00649

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

All data sets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

IPD Sharing Time Frame

With publication

IPD Sharing Access Criteria

Data are available from PI on reasonable request (manuel.luque@salud.madrid.org)

IPD Sharing Supporting Information Type

  • Study Protocol
  • Statistical Analysis Plan (SAP)
  • Informed Consent Form (ICF)
  • Clinical Study Report (CSR)
  • Analytic Code

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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