search
Back to results

Hormone Replacement for Premature Ovarian Insufficiency (HOPE)

Primary Purpose

Primary Ovarian Insufficiency

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Hormone Replacement Therapy
Combined Oral Contraceptives
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Ovarian Insufficiency focused on measuring premature ovarian failure, hormone replacement

Eligibility Criteria

14 Years - 45 Years (Child, Adult)FemaleAccepts Healthy Volunteers

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

Sites / Locations

  • Penn Fertility Care

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Hormone Replacement Therapy

Combined Oral Contraceptives

Arm Description

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).

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)

Outcomes

Primary Outcome Measures

Recruitment
Patient willingness to participate and be randomized

Secondary Outcome Measures

Vasomotor symptoms - Greene Climacteric Scale
Greene Climacteric Scale
Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
Menopausal Vasomotor Symptoms (MVS) survey
Bleeding profile - Bleeding questionnaire
Bleeding questionnaire
Bleeding profile - Menstrual diary
Menstrual diary
Sexual dysfunction - Female Sexual Function Index (FSFI)
Female Sexual Function Index (FSFI)
Satisfaction as Contraceptive Method
Birth Control Satisfaction Assessment
Hormone Assays - FSH (mIU/mL)
FSH (mIU/mL)
Hormone Assays - Estradiol (pg/mL)
Estradiol (pg/mL)
Hormone Assays - Sex-hormone binding globulin (nmol/L)
Sex-hormone binding globulin (nmol/L)
Hormone Assays - Total testosterone (ng/dL)
Total testosterone (ng/dL)
Hormone Assays - Free testosterone (ng/dL)
Free testosterone (ng/dL)
Hormone Assays - Anti-mullerian hormone (pmol/l)
Anti-mullerian hormone (pmol/l)
Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
Dehydroepiandrosterone Sulfate (ng/mL)
Hormone Assays - Thyroid stimulating hormone (U/mL)
Thyroid stimulating hormone (U/mL)
Bone Turnover Markers - Serum osteocalcin (ng/mL)
Serum osteocalcin (ng/mL)
Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
Serum N-telopeptide of type I collagen (nmol/L)
Cardiovascular Risk Markers - Total cholesterol
Total cholesterol (mg/dL)
Cardiovascular Risk Markers - Triglycerides (mg/dL)
Triglycerides (mg/dL)
Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
Lipoprotein a (mg/dL)
Cardiovascular Risk Markers - Fasting glucose (mg/dL)
Fasting glucose (mg/dL)
Cardiovascular Risk Markers - Fasting insulin (pmol/L)
Fasting insulin (pmol/L)
Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
Homeostatic model assessment (HOMA) insulin
Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
Tissue-type plasminogen activator antigen (ng/mL)
Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
Plasma plasminogen activator inhibitor 1 (ng/mL)
Cardiovascular Risk Markers - Fibrinogen (mg/dL)
Fibrinogen (mg/dL)
Cardiovascular Risk Markers - Factor VII (%)
Factor VII (%)
Cardiovascular Risk Markers - C-reactive protein (mg/L)
C-reactive protein (mg/L)

Full Information

First Posted
March 21, 2016
Last Updated
July 3, 2019
Sponsor
University of Pennsylvania
search

1. Study Identification

Unique Protocol Identification Number
NCT02922348
Brief Title
Hormone Replacement for Premature Ovarian Insufficiency
Acronym
HOPE
Official Title
Optimal Hormone Replacement for Women With Premature Ovarian Insufficiency
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Withdrawn
Study Start Date
March 1, 2016 (Actual)
Primary Completion Date
December 1, 2018 (Actual)
Study Completion Date
December 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Pennsylvania

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Ovarian Insufficiency
Keywords
premature ovarian failure, hormone replacement

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Hormone Replacement Therapy
Arm Type
Experimental
Arm Description
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).
Arm Title
Combined Oral Contraceptives
Arm Type
Experimental
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Hormone Replacement Therapy
Other Intervention Name(s)
Estradiol, Prometrium, Micronized progestin, Medroxyprogesterone, Climera, Provera
Intervention Description
Hormone replacement therapy as indicated in Arm 1
Intervention Type
Drug
Intervention Name(s)
Combined Oral Contraceptives
Other Intervention Name(s)
Ethinyl estradiol, Norgestimate
Intervention Description
Combined oral contraceptives as indicated in Arm 2
Primary Outcome Measure Information:
Title
Recruitment
Description
Patient willingness to participate and be randomized
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Vasomotor symptoms - Greene Climacteric Scale
Description
Greene Climacteric Scale
Time Frame
1 year
Title
Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
Description
Menopausal Vasomotor Symptoms (MVS) survey
Time Frame
1 year
Title
Bleeding profile - Bleeding questionnaire
Description
Bleeding questionnaire
Time Frame
1 year
Title
Bleeding profile - Menstrual diary
Description
Menstrual diary
Time Frame
1 year
Title
Sexual dysfunction - Female Sexual Function Index (FSFI)
Description
Female Sexual Function Index (FSFI)
Time Frame
1 year
Title
Satisfaction as Contraceptive Method
Description
Birth Control Satisfaction Assessment
Time Frame
1 year
Title
Hormone Assays - FSH (mIU/mL)
Description
FSH (mIU/mL)
Time Frame
1 year
Title
Hormone Assays - Estradiol (pg/mL)
Description
Estradiol (pg/mL)
Time Frame
1 year
Title
Hormone Assays - Sex-hormone binding globulin (nmol/L)
Description
Sex-hormone binding globulin (nmol/L)
Time Frame
1 year
Title
Hormone Assays - Total testosterone (ng/dL)
Description
Total testosterone (ng/dL)
Time Frame
1 year
Title
Hormone Assays - Free testosterone (ng/dL)
Description
Free testosterone (ng/dL)
Time Frame
1 year
Title
Hormone Assays - Anti-mullerian hormone (pmol/l)
Description
Anti-mullerian hormone (pmol/l)
Time Frame
1 year
Title
Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
Description
Dehydroepiandrosterone Sulfate (ng/mL)
Time Frame
1 year
Title
Hormone Assays - Thyroid stimulating hormone (U/mL)
Description
Thyroid stimulating hormone (U/mL)
Time Frame
1 year
Title
Bone Turnover Markers - Serum osteocalcin (ng/mL)
Description
Serum osteocalcin (ng/mL)
Time Frame
1 year
Title
Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
Description
Serum N-telopeptide of type I collagen (nmol/L)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Total cholesterol
Description
Total cholesterol (mg/dL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Triglycerides (mg/dL)
Description
Triglycerides (mg/dL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
Description
Lipoprotein a (mg/dL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Fasting glucose (mg/dL)
Description
Fasting glucose (mg/dL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Fasting insulin (pmol/L)
Description
Fasting insulin (pmol/L)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
Description
Homeostatic model assessment (HOMA) insulin
Time Frame
1 year
Title
Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
Description
Tissue-type plasminogen activator antigen (ng/mL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
Description
Plasma plasminogen activator inhibitor 1 (ng/mL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Fibrinogen (mg/dL)
Description
Fibrinogen (mg/dL)
Time Frame
1 year
Title
Cardiovascular Risk Markers - Factor VII (%)
Description
Factor VII (%)
Time Frame
1 year
Title
Cardiovascular Risk Markers - C-reactive protein (mg/L)
Description
C-reactive protein (mg/L)
Time Frame
1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
14 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
Penn Fertility Care
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Hormone Replacement for Premature Ovarian Insufficiency

We'll reach out to this number within 24 hrs