Primary Ovarian InsufficiencyPhase 3HOPENCT02922348
Hormone Replacement for Premature Ovarian Insufficiency
A Phase 3 study testing Hormone Replacement Therapy and Combined Oral Contraceptives in people with Primary Ovarian Insufficiency, run by University of Pennsylvania at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 14 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Primary Ovarian Insufficiency
- What is being tested?
- Hormone Replacement Therapy and Combined Oral Contraceptives
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2016to 1 Dec 2018
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 14 to 45 years
- Women only
- Healthy volunteers accepted
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn Fertility Care
Philadelphia, Pennsylvania, 19104
About this study
Official title: 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.
Read the 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.
- Conditions
- Primary Ovarian Insufficiency
- Being tested
- Hormone Replacement Therapy, Combined Oral Contraceptives
- Keywords
- premature ovarian failure, hormone replacement
- Medical subject headings
- Primary Ovarian Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hormone Replacement TherapyDrug
Also called Estradiol, Prometrium, Micronized progestin, Medroxyprogesterone
Hormone replacement therapy as indicated in Arm 1
Combined Oral ContraceptivesDrug
Also called Ethinyl estradiol, Norgestimate
Combined oral contraceptives as indicated in Arm 2
| Study group | Role | What they receive |
|---|---|---|
| Hormone Replacement Therapy | Experimental | 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). Receives: Drug: Hormone Replacement Therapy |
| Combined Oral Contraceptives | Experimental | 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) Receives: Drug: Combined Oral Contraceptives |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment
Patient willingness to participate and be randomized
Measured: 1 year
Secondary outcomes (27)
Vasomotor symptoms - Greene Climacteric Scale
Greene Climacteric Scale
Measured: 1 year
Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
Menopausal Vasomotor Symptoms (MVS) survey
Measured: 1 year
Bleeding profile - Bleeding questionnaire
Bleeding questionnaire
Measured: 1 year
Bleeding profile - Menstrual diary
Menstrual diary
Measured: 1 year
Sexual dysfunction - Female Sexual Function Index (FSFI)
Female Sexual Function Index (FSFI)
Measured: 1 year
Satisfaction as Contraceptive Method
Birth Control Satisfaction Assessment
Measured: 1 year
Hormone Assays - FSH (mIU/mL)
FSH (mIU/mL)
Measured: 1 year
Hormone Assays - Estradiol (pg/mL)
Estradiol (pg/mL)
Measured: 1 year
Hormone Assays - Sex-hormone binding globulin (nmol/L)
Sex-hormone binding globulin (nmol/L)
Measured: 1 year
Hormone Assays - Total testosterone (ng/dL)
Total testosterone (ng/dL)
Measured: 1 year
Hormone Assays - Free testosterone (ng/dL)
Free testosterone (ng/dL)
Measured: 1 year
Hormone Assays - Anti-mullerian hormone (pmol/l)
Anti-mullerian hormone (pmol/l)
Measured: 1 year
Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
Dehydroepiandrosterone Sulfate (ng/mL)
Measured: 1 year
Hormone Assays - Thyroid stimulating hormone (U/mL)
Thyroid stimulating hormone (U/mL)
Measured: 1 year
Bone Turnover Markers - Serum osteocalcin (ng/mL)
Serum osteocalcin (ng/mL)
Measured: 1 year
Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
Serum N-telopeptide of type I collagen (nmol/L)
Measured: 1 year
Cardiovascular Risk Markers - Total cholesterol
Total cholesterol (mg/dL)
Measured: 1 year
Cardiovascular Risk Markers - Triglycerides (mg/dL)
Triglycerides (mg/dL)
Measured: 1 year
Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
Lipoprotein a (mg/dL)
Measured: 1 year
Cardiovascular Risk Markers - Fasting glucose (mg/dL)
Fasting glucose (mg/dL)
Measured: 1 year
Cardiovascular Risk Markers - Fasting insulin (pmol/L)
Fasting insulin (pmol/L)
Measured: 1 year
Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
Homeostatic model assessment (HOMA) insulin
Measured: 1 year
Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
Tissue-type plasminogen activator antigen (ng/mL)
Measured: 1 year
Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
Plasma plasminogen activator inhibitor 1 (ng/mL)
Measured: 1 year
Cardiovascular Risk Markers - Fibrinogen (mg/dL)
Fibrinogen (mg/dL)
Measured: 1 year
Cardiovascular Risk Markers - Factor VII (%)
Factor VII (%)
Measured: 1 year
Cardiovascular Risk Markers - C-reactive protein (mg/L)
C-reactive protein (mg/L)
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2016 (estimated)
- Study start1 Mar 2016
- Primary completion1 Dec 2018
- Study completion1 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Primary Ovarian InsufficiencyStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02922348
- Sponsor's protocol ID
- 823553
- Acronym
- HOPE
- Status last verified
- Jul 2019
- First submitted
- 21 Mar 2016
- Last updated
- 5 Jul 2019
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimal Hormone Replacement for Women With Premature Ovarian Insufficiency
- ClinicalTrials.gov ID
- NCT02922348
- Acronym / sponsor ID
- HOPE / 823553
- Conditions
- Primary Ovarian Insufficiency
- Keywords
- premature ovarian failure, hormone replacement
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Mar 2016 (actual)
- Primary completion
- 1 Dec 2018 (actual)
- Study completion
- 1 Dec 2018 (actual)
- First posted
- 4 Oct 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hormone Replacement Therapy | Experimental | Drug: Hormone Replacement TherapyPatient 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). |
| Combined Oral Contraceptives | Experimental | Drug: Combined Oral ContraceptivesPatients 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) |
Who may qualify
- Ages
- 14 to 45 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hormone Replacement TherapyAlso: Estradiol, Prometrium, Micronized progestin, MedroxyprogesteroneHormone replacement therapy as indicated in Arm 1 | Drug | Hormone Replacement Therapy |
| Combined Oral ContraceptivesAlso: Ethinyl estradiol, NorgestimateCombined oral contraceptives as indicated in Arm 2 | Drug | Combined Oral Contraceptives |
Primary outcome
Recruitment
Time frame: 1 year
Patient willingness to participate and be randomized
27 secondary outcomes
Vasomotor symptoms - Greene Climacteric Scale
Time frame: 1 year
Vasomotor symptoms - Menopausal Vasomotor Symptoms (MVS) survey
Time frame: 1 year
Bleeding profile - Bleeding questionnaire
Time frame: 1 year
Bleeding profile - Menstrual diary
Time frame: 1 year
Sexual dysfunction - Female Sexual Function Index (FSFI)
Time frame: 1 year
Satisfaction as Contraceptive Method
Time frame: 1 year
Hormone Assays - FSH (mIU/mL)
Time frame: 1 year
Hormone Assays - Estradiol (pg/mL)
Time frame: 1 year
Hormone Assays - Sex-hormone binding globulin (nmol/L)
Time frame: 1 year
Hormone Assays - Total testosterone (ng/dL)
Time frame: 1 year
Hormone Assays - Free testosterone (ng/dL)
Time frame: 1 year
Hormone Assays - Anti-mullerian hormone (pmol/l)
Time frame: 1 year
Hormone Assays - Dehydroepiandrosterone Sulfate (ng/mL)
Time frame: 1 year
Hormone Assays - Thyroid stimulating hormone (U/mL)
Time frame: 1 year
Bone Turnover Markers - Serum osteocalcin (ng/mL)
Time frame: 1 year
Bone Turnover Markers - Serum N-telopeptide of type I collagen (nmol/L)
Time frame: 1 year
Cardiovascular Risk Markers - Total cholesterol
Time frame: 1 year
Cardiovascular Risk Markers - Triglycerides (mg/dL)
Time frame: 1 year
Cardiovascular Risk Markers - Lipoprotein a (mg/dL)
Time frame: 1 year
Cardiovascular Risk Markers - Fasting glucose (mg/dL)
Time frame: 1 year
Cardiovascular Risk Markers - Fasting insulin (pmol/L)
Time frame: 1 year
Cardiovascular Risk Markers - Homeostatic model assessment (HOMA) insulin
Time frame: 1 year
Cardiovascular Risk Markers - Tissue-type plasminogen activator antigen (ng/mL)
Time frame: 1 year
Cardiovascular Risk Markers - Plasma plasminogen activator inhibitor 1 (ng/mL)
Time frame: 1 year
Cardiovascular Risk Markers - Fibrinogen (mg/dL)
Time frame: 1 year
Cardiovascular Risk Markers - Factor VII (%)
Time frame: 1 year
Cardiovascular Risk Markers - C-reactive protein (mg/L)
Time frame: 1 year
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2019.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Hormone Replacement Therapy and Combined Oral Contraceptives in people with Primary Ovarian Insufficiency, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 5 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2019.