Hormone Replacement for Premature Ovarian Insufficiency (HOPE)

July 3, 2019 updated by: University of Pennsylvania

Optimal Hormone Replacement for Women With Premature Ovarian Insufficiency

The investigators intend to establish feasibility/acceptability of a pilot randomized trial comparing hormone replacement therapy (HRT) and combined oral contraceptives (COCs) in women with premature ovarian insufficiency to estimate differences in quality of life (QOL) and serum hormone assays and markers of bone turnover/cardiovascular risk. At baseline, QOL survey will be administered and serum testing performed. Patients then randomized to HRT or COCs. Repeat testing will be performed after 3 and 6 months.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Premature ovarian insufficiency (POI) is a term used to describe when a woman's ovaries stop working normally before the natural age of menopause. Early sequelae of POI include vasomotor symptoms, vaginal dryness, mood swings and insomnia due to estrogen deficiency. Long-term sequelae such as loss of bone mineral density and cardiovascular risk carry are considerable concerns. While exogenous estrogen replacement is recommended for the POI patient population, the optimal regimen for replacement is not clear. One approach to hormone replacement therapy (HRT) is to mimic physiologic ovarian function through full replacement doses of estrogen (either orally or transdermally) to reach the typical serum estradiol levels of a menstruating woman (approximately 104 pg/mL per day) with cyclic progestin therapy for endometrial protection. Another approach uses daily combined estrogen-progestin oral contraceptives (COCs), for ease of administration and increased social acceptability. To date, few studies have been performed comparing the two treatment methods in terms of quality of life measures (vasomotor symptoms, bleeding profile, sexual dysfunction, satisfaction with contraception), endocrine function, bone turnover or cardiovascular risk in POI patients. In this proposal, the investigators intend to establish feasibility and acceptability of a pilot randomized controlled trial comparing traditional HRT with COCs in women with POI and to evaluate differences in quality of life measures, hormone assays, bone turnover and cardiovascular risk between treatment arms. The investigators hypothesize that acceptability and feasibility of the pilot trial will be high and that differences will be detected for all measured variables between treatment arms. Demonstration of feasibility and acceptability of this pilot would allow for the pursuit of a larger trial and identification of a superior treatment regimen would have a meaningful impact on the short and long-term care of this patient population.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Penn Fertility Care

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years to 45 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Female patients,
  • Between 14-45 years of age
  • Post-menarchal
  • Presence of uterus
  • POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea), elevated serum serum follicle stimulating hormone (FSH), low serum estradiol concentrations, or estrogen deficiency symptoms.

Exclusion Criteria:

  • Pregnancy or lactation within previous 3 months
  • Use of hormonal contraception or replacement within previous 3 months
  • Any contraindication to oral contraceptive pills or hormone replacement therapy per the current drug labels. These could include, but are not limited to: history of venous thromboembolism,estrogen-sensitive cancer history, regular cigarette smoking and history of or active liver disease, etc.
  • Patients will be screened for pregnancy with a urine HCG test at time of screening

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Hormone Replacement Therapy
Patient will be given hormones in the form of: transdermal estradiol patch (Climara) 100 mcg/24 hours weekly, progesterone (Prometrium) 200 mg per day for first 12 calendar days of each month (If patients insurance plan does not cover transdermal estradiol, they will be prescribed oral estradiol 2 mg daily. If patients insurance plan does not cover Prometrium, they will be prescribed medroxyprogesterone (Provera) 10 mg per day for first 12 calendar days of each month).
Drug: Hormone Replacement Therapy
Hormone replacement therapy as indicated in Arm 1
Other Names:
  • Prometrium
  • Provera
  • Estradiol
  • Micronized progestin
  • Medroxyprogesterone
  • Climera
Experimental: Combined Oral Contraceptives
Patients will be given hormones in the form of: monophasic combined oral contraceptive containing ethinyl estradiol 0.035 mg and norgestimate 0.25 mg, 1 tablet daily (21 days of active pills and 7 days of inactive pills)
Drug: Combined Oral Contraceptives
Combined oral contraceptives as indicated in Arm 2
Other Names:
  • Ethinyl estradiol
  • Norgestimate

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recruitment
Time Frame: 1 year
Patient willingness to participate and be randomized
1 year

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Vasomotor symptoms - Greene Climacteric Scale
Time Frame: 1 year
Greene Climacteric Scale
1 year
Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
Time Frame: 1 year
Menopausal Vasomotor Symptoms (MVS) survey
1 year
Bleeding profile - Bleeding questionnaire
Time Frame: 1 year
Bleeding questionnaire
1 year
Bleeding profile - Menstrual diary
Time Frame: 1 year
Menstrual diary
1 year
Sexual dysfunction - Female Sexual Function Index (FSFI)
Time Frame: 1 year
Female Sexual Function Index (FSFI)
1 year
Satisfaction as Contraceptive Method
Time Frame: 1 year
Birth Control Satisfaction Assessment
1 year
Hormone Assays - FSH (mIU/mL)
Time Frame: 1 year
FSH (mIU/mL)
1 year
Hormone Assays - Estradiol (pg/mL)
Time Frame: 1 year
Estradiol (pg/mL)
1 year
Hormone Assays - Sex-hormone binding globulin (nmol/L)
Time Frame: 1 year
Sex-hormone binding globulin (nmol/L)
1 year
Hormone Assays - Total testosterone (ng/dL)
Time Frame: 1 year
Total testosterone (ng/dL)
1 year
Hormone Assays - Free testosterone (ng/dL)
Time Frame: 1 year
Free testosterone (ng/dL)
1 year
Hormone Assays - Anti-mullerian hormone (pmol/l)
Time Frame: 1 year
Anti-mullerian hormone (pmol/l)
1 year
Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
Time Frame: 1 year
Dehydroepiandrosterone Sulfate (ng/mL)
1 year
Hormone Assays - Thyroid stimulating hormone (U/mL)
Time Frame: 1 year
Thyroid stimulating hormone (U/mL)
1 year
Bone Turnover Markers - Serum osteocalcin (ng/mL)
Time Frame: 1 year
Serum osteocalcin (ng/mL)
1 year
Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
Time Frame: 1 year
Serum N-telopeptide of type I collagen (nmol/L)
1 year
Cardiovascular Risk Markers - Total cholesterol
Time Frame: 1 year
Total cholesterol (mg/dL)
1 year
Cardiovascular Risk Markers - Triglycerides (mg/dL)
Time Frame: 1 year
Triglycerides (mg/dL)
1 year
Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
Time Frame: 1 year
Lipoprotein a (mg/dL)
1 year
Cardiovascular Risk Markers - Fasting glucose (mg/dL)
Time Frame: 1 year
Fasting glucose (mg/dL)
1 year
Cardiovascular Risk Markers - Fasting insulin (pmol/L)
Time Frame: 1 year
Fasting insulin (pmol/L)
1 year
Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
Time Frame: 1 year
Homeostatic model assessment (HOMA) insulin
1 year
Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
Time Frame: 1 year
Tissue-type plasminogen activator antigen (ng/mL)
1 year
Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
Time Frame: 1 year
Plasma plasminogen activator inhibitor 1 (ng/mL)
1 year
Cardiovascular Risk Markers - Fibrinogen (mg/dL)
Time Frame: 1 year
Fibrinogen (mg/dL)
1 year
Cardiovascular Risk Markers - Factor VII (%)
Time Frame: 1 year
Factor VII (%)
1 year
Cardiovascular Risk Markers - C-reactive protein (mg/L)
Time Frame: 1 year
C-reactive protein (mg/L)
1 year

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Pennsylvania

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2016

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2018

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 21, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 29, 2016

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 4, 2016

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 5, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 3, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 823553

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings