Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Oophorectomy, Estrogen Therapy and Cardiovascular Disease Risk in Young Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03815929
Recruitment Status : Recruiting
First Posted : January 24, 2019
Last Update Posted : August 16, 2019
Sponsor:
Information provided by (Responsible Party):
Ekta Kapoor, Mayo Clinic

Brief Summary:
Researchers are trying to assess the appropriate dose of estrogen for decreasing the risk of cardiovascular disease in women who have removal of their ovaries at a young age, before the age of 46 years.

Condition or disease Intervention/treatment Phase
Cardiovascular Risk Reduction Drug: Estradiol 100 Micrograms Patch Drug: Estradiol Patch Phase 2

Detailed Description:

Baseline Study Visit: Subjects will report for the Baseline Study Day in an 8 hour fasting state (water only) and refrain from heavy exercise, caffeine, and alcohol for 24 hours. The participant will undergo study specific procedures including a urine pregnancy test if they are of child bearing potential. Participants will also complete a set of questionnaires. After the completion of the study tests, participants will be offered a meal.

Participants scheduled for surgery to remove their ovaries: after the surgery subjects will be randomized to one of two groups. They will receive the standard dose of the hormone (estrogen) patch, generally prescribed to patients after removal both ovaries. Or sent home on the standard dose hormone patch, hormone levels will be tested every 3-4 weeks, and patch dose adjusted until the estrogen level is reached that results in the hormone levels of a young woman before menopause. In order to check hormones, subjects will be able to choose to have a lab kit sent to them and have the draw done locally, or can come in person.

Participants will also receive a second hormone prescription if they have an intact uterus to protect the lining of the uterus from the effects of using estrogen alone.

6-Month Study Visit: Subjects will be asked to come back and repeat most of the study specific tests from the baseline study visit that will take about 5 hours.

1-Year Study Visit: Subjects will be asked to come back for the final visit and will repeat all the study tests done at baseline visit. This visit will take about 5 hours.

Control Group: Healthy subjects serving as controls to see how measures change over time will not undergo a surgery or be given estrogen. These healthy subjects will return after the baseline visit to repeat study visits at 6 and 12-months.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model Description: Subject be placed into three different study arms. Subjects undergoing surgery will be randomized to receive either standard hormone therapy or individualized hormone therapy. These arms will be compared against each other as well as a third arm of healthy timed-control subjects
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Impact of Individualized Estrogen Therapy on Cardiovascular Disease Risk Parameters in Young Women After Bilateral Oophorectomy: A Randomized Controlled Trial
Actual Study Start Date : March 15, 2019
Estimated Primary Completion Date : August 2023
Estimated Study Completion Date : November 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Estradiol

Arm Intervention/treatment
Active Comparator: Standard replacement therapy regimen
100 mcg transdermal estradiol patch (or equivalent oral dose)
Drug: Estradiol 100 Micrograms Patch
Standard

Active Comparator: Titrated replacement therapy regimen
Transdermal estradiol patch (or equivalent oral dose) titrated to achieve pre-menopausal estradiol level
Drug: Estradiol Patch
Individualized

No Intervention: Timed Control Group
Healthy age-matched subjects not on hormone therapy



Primary Outcome Measures :
  1. Change in Endothelial function [ Time Frame: Baseline, 6 months, and 12 months ]
    Brachial artery flow mediated dilation using ultrasonography to measure any endothelium dysfunction occurring over 12 months.

  2. Change in cerebral vascular reactivity [ Time Frame: Baseline, 6 months, and 12 months ]
    Changes to the middle cerebral artery blood flow velocity measured using a Multigon Trans-Cranial Doppler sonogram probe monitoring with three stepwise end-tidal carbon dioxide elevations of constant concentration levels with 3 minutes at each level is compared over planned time frames.


Secondary Outcome Measures :
  1. Change in Arterial tonometry [ Time Frame: Baseline, 6 months, and 12 months ]
    Arterial stiffness is recorded through high-fidelity pressure waveforms and compared at planned time frames

  2. Changes in maximal Voluntary Contraction of the non-dominant arm [ Time Frame: Baseline, 6 months, and 12 months ]
    Isometric handgrip exercise squeezing a transducer with goal of consistently maintaining a moderate workload average over 5 attempts and compared over time.

  3. Changes to the index of baroreflex sensitivity [ Time Frame: Baseline, 6 months, and 12 months ]
    Colder pressor test immersing hand up to wrist in ice water while changes in blood pressure and heart rate are monitored and compared over time frames.

  4. Changes in measurements of whole body and regional fat and fat-free mass [ Time Frame: Baseline and 12 months ]
    Measurements will be taken using Dual energy x-ray absorptiometry (DXA) scans and compared over time and between the groups.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Premenopausal women undergoing (or completion of a) bilateral oophorectomy for non-malignant diagnoses at Mayo Clinic, Rochester; or premenopausal women not undergoing the procedure for the timed control group
  • Currently between the ages of 21- 45 years
  • Able to participate fully in all aspects of the study
  • Able to understand and sign the informed consent.

Exclusion Criteria:

  • History of hepatic, renal, or hematological diseases
  • History of venous thromboembolism; peripheral vascular disease; coronary artery disease; stroke/neurovascular disease
  • Chemotherapy or radiation therapy in the preceding 3 months
  • Current tobacco use
  • Current use of medication that alters autonomic or vascular function (e.g. tricyclic antidepressants, α-blockers, β-blockers, etc.) or aromatase inhibitor/tamoxifen therapy
  • Contra-indication to estrogen use
  • Current or previous diagnosis of breast and endometrial cancer
  • For Timed Controls: Are currently pregnant or lactating, or are of child-bearing potential or are likely to become pregnant during the study and unwilling to use contraception; Acceptable forms include:Barrier methods (such as a condom or diaphragm) used with a spermicide (a foam, cream, or gel that kills sperm), Copper Intra Uterine Device, Hysterectomy, Tubal ligation, Abstinence (no sex)
  • Any condition or factor judged by the investigator to preclude participation in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03815929


Contacts
Layout table for location contacts
Contact: Shawn C Fokken, BS, CCRP 507-293-2740 fokken.shawn@mayo.edu
Contact: Pamela A. Engrav 507-775-6938 engrav.pamela@mayo.edu

Locations
Layout table for location information
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55902
Contact: Shawn C Fokken    507-293-2740    fokken.shawn@mayo.edu   
Contact: Pam Engrav    507-775-6938    engrav.pamela@mayo.edu   
Principal Investigator: Ekta Kapoor, MBBS         
Sponsors and Collaborators
Mayo Clinic
Investigators
Layout table for investigator information
Principal Investigator: Ekta Kapoor, MBBS Mayo Clinic

Additional Information:
Layout table for additonal information
Responsible Party: Ekta Kapoor, Principal Investigator, Mayo Clinic
ClinicalTrials.gov Identifier: NCT03815929     History of Changes
Other Study ID Numbers: 18-007999
First Posted: January 24, 2019    Key Record Dates
Last Update Posted: August 16, 2019
Last Verified: August 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ekta Kapoor, Mayo Clinic:
Hormone therapy
Pre-menopausal Oophorectomy
Cardiovascular Disease

Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiovascular Diseases
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Estradiol
Polyestradiol phosphate
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female