Primary Ovarian InsufficiencyPhase 1/2NCT05737329

Efficacy, Safety, and Tolerability of Higher Doses Estrogen Therapy in Women With Premature Ovarian Insufficiency

A Phase 1/2 study testing Transdermal estradiol gel 0.1% 1.5mg/ day and Transdermal estradiol gel 0.1% 2.0mg/ day in people with Primary Ovarian Insufficiency, run by Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare at 1 site in Russia.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record

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Trial summary

The goal of this study is to assess the effects of higher doses versus standard hormone therapy on quality of life (QoL), symptoms due to estrogen deficiency, and bone health in women with premature ovarian insufficiency (POI). Read more about this study

Who is it for?: Ages 18 to 45 years, women only
Conditions the study is for: Primary Ovarian Insufficiency
What is being tested?: Transdermal estradiol gel 0.1% 1.5mg/ day and Transdermal estradiol gel 0.1% 2.0mg/ day
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 80 participants
Where: 1 siteRussia
Study dates: 1 Mar 2019to Apr 2023
Phase: Phase 1/2
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 18 to 45 years
Women only
No healthy volunteers
Adult

Who may be able to join

Patients with karyotypically normal spontaneous POI diagnosed before the age of 40. POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea for at least 4 months), elevated serum follicle stimulating hormone (FSH ≥ 25 IU/L with 4 to 6 weeks interval)
Between 18-45 years of age
Use of standard-dose estradiol HRT (Estradiol 2 mg+ Dydrogesterone10 mg) for at least the last 12 months
Signed informed consent before inclusion in the study

Who cannot join

Any contraindication to HRT 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, bleeding from the genital tract of unknown origin, etc.
POI due to cytotoxic chemotherapy or radiation therapy, surgery
Diseases that may be associated with hot flashes (such as pheochromocytoma, hyperthyroidism, medullary carcinoma of the thyroid, acromegaly, pancreatic islet-cell tumors, renal cell carcinoma, carcinoid syndrome, systemic mast cell disease, neurological flushing, emotional flushing, spinal cord injury)
Taking medications that can also cause hot flashes (such as Tamoxifen, Raloxifene, Tricyclic antidepressants, Monoamine oxidase inhibitors, Calcium channel blockers, Depo leuprolide, Clomiphene, Serotonin uptake inhibitors)
Severe somatic conditions (uncontrolled hypertension, kidney disease, liver disease, etc.)
Diseases with impaired thyroid and adrenal gland function
Refusal to participate

Trial locations and contacts

1 site in 1 country.

Russia1 site

Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of Healthcare
Moscow, 117997

Other trials in Russia

About this study

Official title: Optimization of Management Tactics for Women With Premature Ovarian Insufficiency, Taking Into Account Their Clinical and Hormonal Profile

The efficacy of the hormonal treatment will be assessed clinically and also by measuring serum concentrations of Estradiol (E2), Follicle-Stimulating Hormone (FSH), Luteinizing hormone (LH), total Testosterone (T), Estrone (E1), E1 sulfate (E1S), and Sex Hormone Binding Globulin (SHBG). Bone mineral density (BMD) will be measured using dual-energy X-ray absorptiometry. Safety will be assessed by measuring endometrial thickness with Gynecological transvaginal ultrasound (TVS), treatment-related adverse events (AEs) and treatment-emergent AEs monitoring.

Conditions: Primary Ovarian Insufficiency
Being tested: Transdermal estradiol gel 0.1% 1.5mg/ day, Transdermal estradiol gel 0.1% 2.0mg/ day
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.

Transdermal estradiol gel 0.1% 1.5mg/ dayDrug
Estradiol gel 0.1% 1.5mg/ daily + Micronized Progesterone 200mg
Transdermal estradiol gel 0.1% 2.0mg/ dayDrug
Estradiol gel 0.1% 2.0mg/ daily + Micronized Progesterone 200mg

Study groups in NCT05737329
Study group	Role	What they receive
Transdermal estradiol gel 0.1% 1.5mg/ day	Other	Patient will be given Hormone Replacement Therapy (HRT) in the form of: Transdermal estradiol gel 0.1% 1.5mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle. Receives: Drug: Transdermal estradiol gel 0.1% 1.5mg/ day; Drug: Transdermal estradiol gel 0.1% 2.0mg/ day
Transdermal estradiol gel 0.1% 2.0mg/ day	Other	Patient with insufficient effect from previous treatment estradiol gel 0.1% 1.5mg will be given HRT in the form of: Transdermal estradiol gel 0.1% 2.0mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle. Receives: Drug: Transdermal estradiol gel 0.1% 1.5mg/ day; Drug: Transdermal estradiol gel 0.1% 2.0mg/ day

What is being measured

The primary outcome is the main question the study is designed to answer.

Evaluation of the severity of estrogen deficiency symptoms
The Green scale questionnaire was used initially and after 3 months against the background of HRT. The questionnaire includes 21 questions from 0 to 3 points, where a lower score means a better result.
Measured: 3 months
Changing the assessment of quality of life using the Short Form Health Survey-36 (SF-36)
The SF-36 is a generic QoL instrument. It consists of 36 items organized into eight domains: Physical Function (AF), Physical Role Function (RF), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Emotional Role Function (RE), and Mental Health (SM) as well as an item on the change of General Health. The scores of each domain have been converted into a scale from 0 to 100. Lower scores are indicative of worse conditions.
Measured: 3 months
Changing the assessment of menopause-related quality of life measured using the Menopause-Specific Quality of Life (MENQOL) questionnaire.
The MENQOL questionnaire is a self-administered instrument. This validated questionnaire (range 1-8) assesses four quality of life domains; physical (16 items), vasomotor (3 items), psychosocial (7 items) and sexual (3 items). Scoring generates 4 domain scores and a total score, the mean of the 4 domain scores. Identical scoring for each of the four MENQOL domains is used. A "0" is identical that the woman has not experienced this specific symptom in the previous month; Score "1" demonstrates that the woman experienced the symptom, but it did not bother her; Scores "2" through "7" demonstrate an increasing level of the bothering symptom, so that these scores indicate increasing levels of bother experienced from the symptom and correspond to the ''1'' through ''6'' checkboxes on the MENQOL. With increasing MENQOL scores, levels of bother experienced from the symptom are increased as well.
Measured: 3 months

Secondary outcomes (7)

Сhanges in the level of sex hormones after using higher doses estrogen therapy
Assessment of changes in the level of sex hormone in peripheral blood: estradiol (pmol/l). Reference values: 150 - 450 pmol/l. Blood sampling is performed at baseline and after 3 months.
Measured: Assessment of changes in the level of sex hormone in peripheral blood: testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.
Сhanges in the level of sex hormones after using higher doses estrogen therapy
Assessment of changes in the level of sex hormone in peripheral blood: total testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.
Measured: 3 months
Сhanges in the level of FSH after using higher doses estrogen therapy
Measured: 3 months
Сhanges in the level of E1 after using higher doses estrogen therapy
Measured: 3 months
Сhanges in the level of E1S after using higher doses estrogen therapy
Measured: 3 months
Сhanges in the level of SHBG after using higher doses estrogen therapy
Measured: 3 months
Bone mineral density (BMD) response to using higher doses estrogen therapy for 12 Months
Measured: 12 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Mar 2019Apr 2023

First posted21 Feb 2023
Study start1 Mar 2019
Primary completionApr 2023 (estimated)
Study completionApr 2023 (estimated)

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.
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 1/2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Model description: Women with POI taking standard-dose estradiol hormone replacement therapy (E2/dydrogesterone (oral) (2.0/10 mg)) were invited to the study. We conducted a pilot study designed to compare the effectiveness of oral estradiol (2mg/ day) and Transdermal estradiol gel 0.1% (Gel sachet 1.0mg/ day) as standard-dose estradiol hormone replacement therapy. The obtained results on the absence of a significant difference in the effect of the above therapy made it possible to justify the prescription of higher doses of estrogens without prior switching from oral to transdermal therapy in equivalent doses in all study participants. Study participants will consistently receive Transdermal estradiol gel 0.1% (Gel sachet 1.5mg/ day) and Transdermal estradiol gel 0.1% (Gel sachet 2.0mg/ day) (both with 200mg micronized progesterone administered vaginally for 14days per cycle) with an outcome assessment at each stage of the study.
Masking: Single blind
Who is masked: Participant
Enrolment: 80 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05737329
Sponsor's protocol ID: №2-07/02.2019
Status last verified: Feb 2023
First submitted: 10 Feb 2023
Last updated: 28 Feb 2023
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
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Oral GDC-0077 in Premature Ovarian Insufficiency
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RecruitingPhase 3
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All Primary Ovarian Insufficiency trials

Study at a glance

From the registry record, last updated by the sponsor on 28 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Optimization of Management Tactics for Women With Premature Ovarian Insufficiency, Taking Into Account Their Clinical and Hormonal Profile
ClinicalTrials.gov ID: NCT05737329
Acronym / sponsor ID: №2-07/02.2019
Conditions: Primary Ovarian Insufficiency
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Unknown status
Enrolment: 80 participants (actual)
Lead sponsor: Federal State Budget Institution Research Center for Obstetrics, Gynecology and Perinatology Ministry of HealthcareOther government
Study start: 1 Mar 2019 (actual)
Primary completion: Apr 2023 (estimated)
Study completion: Apr 2023 (estimated)
First posted: 21 Feb 2023 (actual)
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.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Sequential
Masking: Single blind (participant)
Number of arms: 2
Model description: Women with POI taking standard-dose estradiol hormone replacement therapy (E2/dydrogesterone (oral) (2.0/10 mg)) were invited to the study. We conducted a pilot study designed to compare the effectiveness of oral estradiol (2mg/ day) and Transdermal estradiol gel 0.1% (Gel sachet 1.0mg/ day) as standard-dose estradiol hormone replacement therapy. The obtained results on the absence of a significant difference in the effect of the above therapy made it possible to justify the prescription of higher doses of estrogens without prior switching from oral to transdermal therapy in equivalent doses in all study participants. Study participants will consistently receive Transdermal estradiol gel 0.1% (Gel sachet 1.5mg/ day) and Transdermal estradiol gel 0.1% (Gel sachet 2.0mg/ day) (both with 200mg micronized progesterone administered vaginally for 14days per cycle) with an outcome assessment at each stage of the study.

Arm	Type	Receives
Transdermal estradiol gel 0.1% 1.5mg/ day	Other	Drug: Transdermal estradiol gel 0.1% 1.5mg/ day, Drug: Transdermal estradiol gel 0.1% 2.0mg/ dayPatient will be given Hormone Replacement Therapy (HRT) in the form of: Transdermal estradiol gel 0.1% 1.5mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.
Transdermal estradiol gel 0.1% 2.0mg/ day	Other	Drug: Transdermal estradiol gel 0.1% 1.5mg/ day, Drug: Transdermal estradiol gel 0.1% 2.0mg/ dayPatient with insufficient effect from previous treatment estradiol gel 0.1% 1.5mg will be given HRT in the form of: Transdermal estradiol gel 0.1% 2.0mg (Gel sachet) in continuous daily regimen. The progesterone component of HRT (200mg micronized progesterone administered vaginally) will be given for 14 days, starting from day 14 through day 28 of each cycle.

Who may qualify

Ages: 18 to 45 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Patients with karyotypically normal spontaneous POI diagnosed before the age of 40. POI as defined by: change in menstrual function (oligomenorrhea and/or amenorrhea for at least 4 months), elevated serum follicle stimulating hormone (FSH ≥ 25 IU/L with 4 to 6 weeks interval)
Between 18-45 years of age
Use of standard-dose estradiol HRT (Estradiol 2 mg+ Dydrogesterone10 mg) for at least the last 12 months
Signed informed consent before inclusion in the study

Key exclusion criteria (7 listed)

Any contraindication to HRT 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, bleeding from the genital tract of unknown origin, etc.
POI due to cytotoxic chemotherapy or radiation therapy, surgery
Diseases that may be associated with hot flashes (such as pheochromocytoma, hyperthyroidism, medullary carcinoma of the thyroid, acromegaly, pancreatic islet-cell tumors, renal cell carcinoma, carcinoid syndrome, systemic mast cell disease, neurological flushing, emotional flushing, spinal cord injury)
Taking medications that can also cause hot flashes (such as Tamoxifen, Raloxifene, Tricyclic antidepressants, Monoamine oxidase inhibitors, Calcium channel blockers, Depo leuprolide, Clomiphene, Serotonin uptake inhibitors)
Severe somatic conditions (uncontrolled hypertension, kidney disease, liver disease, etc.)

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
Transdermal estradiol gel 0.1% 1.5mg/ dayEstradiol gel 0.1% 1.5mg/ daily + Micronized Progesterone 200mg	Drug	Transdermal estradiol gel 0.1% 1.5mg/ day, Transdermal estradiol gel 0.1% 2.0mg/ day
Transdermal estradiol gel 0.1% 2.0mg/ dayEstradiol gel 0.1% 2.0mg/ daily + Micronized Progesterone 200mg	Drug	Transdermal estradiol gel 0.1% 1.5mg/ day, Transdermal estradiol gel 0.1% 2.0mg/ day

Primary outcome

Evaluation of the severity of estrogen deficiency symptoms
Time frame: 3 months
The Green scale questionnaire was used initially and after 3 months against the background of HRT. The questionnaire includes 21 questions from 0 to 3 points, where a lower score means a better result.
Changing the assessment of quality of life using the Short Form Health Survey-36 (SF-36)
Time frame: 3 months
The SF-36 is a generic QoL instrument. It consists of 36 items organized into eight domains: Physical Function (AF), Physical Role Function (RF), Bodily Pain (BP), General Health (GH), Vitality (VT), Social Function (SF), Emotional Role Function (RE), and Mental Health (SM) as well as an item on the change of General Health. The scores of each domain have been converted into a scale from 0 to 100. Lower scores are indicative of worse conditions.
Changing the assessment of menopause-related quality of life measured using the Menopause-Specific Quality of Life (MENQOL) questionnaire.
Time frame: 3 months
The MENQOL questionnaire is a self-administered instrument. This validated questionnaire (range 1-8) assesses four quality of life domains; physical (16 items), vasomotor (3 items), psychosocial (7 items) and sexual (3 items). Scoring generates 4 domain scores and a total score, the mean of the 4 domain scores. Identical scoring for each of the four MENQOL domains is used. A "0" is identical that the woman has not experienced this specific symptom in the previous month; Score "1" demonstrates that the woman experienced the symptom, but it did not bother her; Scores "2" through "7" demonstrate an increasing level of the bothering symptom, so that these scores indicate increasing levels of bother experienced from the symptom and correspond to the ''1'' through ''6'' checkboxes on the MENQOL. With increasing MENQOL scores, levels of bother experienced from the symptom are increased as well.

7 secondary outcomes

Сhanges in the level of sex hormones after using higher doses estrogen therapy
Time frame: Assessment of changes in the level of sex hormone in peripheral blood: testosterone (nmol/l). Reference values: 0,52 - 2,5 nmol/l. Blood sampling is performed at baseline and after 3 months.
Сhanges in the level of sex hormones after using higher doses estrogen therapy
Time frame: 3 months
Сhanges in the level of FSH after using higher doses estrogen therapy
Time frame: 3 months
Сhanges in the level of E1 after using higher doses estrogen therapy
Time frame: 3 months
Сhanges in the level of E1S after using higher doses estrogen therapy
Time frame: 3 months
Сhanges in the level of SHBG after using higher doses estrogen therapy
Time frame: 3 months
Bone mineral density (BMD) response to using higher doses estrogen therapy for 12 Months
Time frame: 12 Months

Results and safety

Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2023.

Related trials for Primary Ovarian Insufficiency

RecruitingPhase 2
Autologous Hair Follicle-Derived Secretome and Platelet-Rich Plasma for Premature Ovarian Insufficiency
Premature Ovarian Insufficiency, POI
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Gonadal Tissue Freezing for Fertility Preservation in Individuals at Risk for Ovarian Dysfunction, Premature Ovarian Insufficiency and Clinically Indicated Gonadectomy
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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.

Victoria Averkova study chair

FSBI "National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I.Kulakov" Ministry of Healthcare of the Russian Federation

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 28 Feb 2023. 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 Russia. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

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?

Evaluation of the severity of estrogen deficiency symptoms (time frame: 3 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05737329.

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 28 Feb 2023.