Menopausal and Other Perimenopausal DisordersNCT01613131

Mirena and Estrogen for Control of Perimenopause Symptoms and Ovulation Suppression

A study testing Mirena and Estradiol in people with Menopausal and Other Perimenopausal Disorders, run by University of Colorado, Denver at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 40 to 52 years, women only
Conditions the study is for: Menopausal and Other Perimenopausal Disorders
What is being tested?: Mirena and Estradiol
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 39 participants
Where: 1 siteUnited States
Study dates: Apr 2012to Jun 2014
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 40 to 52 years
Women only
No healthy volunteers
Adult

Who may be able to join

Age 40-52
History of regular menstrual cycles every 20-35 days in mid-reproductive life (20-35 years of age)
At least 1 period within the past 3 months
BMI less than 35 kg/m2
Presence of at least one of the following perimenopausal symptoms:
Hot flashes (vasomotor symptoms)
Cyclical headache, bloating or adverse mood
Self-reported poor quality of sleep

Who cannot join

Age < 40 years
Hysterectomy or bilateral oophorectomy
Cigarette smoking
Signs or symptoms of restless leg syndrome or sleep apnea
Any chronic renal or hepatic disease that might interfere with excretion of gonadotropins or sex steroids
Moderate/vigorous aerobic exercise > 4 hours per week

Show all 13Show fewer

Inability to read/write English
Pregnant Women
Prisoners
Decisionally challenged subjects
Any medical condition that makes use of Topical estradiol or Mirena contraindicated.
Sex hormone use within the past 30 days
History of cancer, blood clots or blood clotting disorder

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Colorado
Aurora, Colorado, 80045

Other trials in United States

About this study

Official title: Effectiveness of Perimenopausal Hormone Therapy in Suppression of Ovulation, Stabilization of Reproductive Hormones and Symptom Control

Hormonal treatment of perimenopausal women has frequently utilized oral contraceptive pills (OCPs). Because of their ability to suppress ovulation and establish cycle control, OCPs have become a popular option, and one that is FDA approved for use until menopause. However, use of OCPs in women in their 40's and 50's carries significant cardiovascular risks. Venous thromboembolism risk is 3-6 fold greater in OCP users, and the risk of myocardial infarction (MI) is approximately doubled in OCP users over the age of 40. This occurs at an age where the background population risk of MI begins to increase, such that the absolute number of cases rises substantially. Women with additional risk factors for cardiovascular disease have a much greater risk for MI (6-40-fold) in association with OCPs. There are also large subgroups of midlife women who are not candidates for OCP use, such a smokers and migraineurs. Moreover, the trend towards lower estrogen dosing with OCPs containing 20 micrograms of ethinyl estradiol has not led to a detectable decrease in thromboembolic risk.

Because of their increased potential risks, it is appropriate to seek alternatives to OCPs and to explore lower doses of hormones to relieve perimenopausal symptoms that occur prior to a woman's final menses. Recent evidence indicates that the hypothalamic-pituitary axis of reproductively aging women is more susceptible to suppression by sex steroids that previously believed. It is possible that hormone doses as low as 50 micrograms of transdermal estradiol (TDE) can suppress the hypothalamic-pituitary axis of midlife women. It is also tempting to speculate that the low but measurable circulating doses of levonorgestrel that are present when a woman uses the Mirena intrauterine system (IUS) can contribute to or even independently suppress the hypothalamic-pituitary axis, and reduce the hormonal fluctuations that result in worsening of perimenopausal symptoms. The combination of low dose TDE plus Mirena may therefore confer superior symptom control as well as contraceptive effectiveness, at far less risk.

Read the detailed description

The Specific Aims of the present proposal are therefore as follows:

Aim 1: To test the hypothesis that low dose estrogen therapy in concert with the low doses of levonorgestrel that circulate when Mirena is used will suppress ovulation in perimenopausal women.

Aim 2: To examine ovulation rates and symptom control with Mirena alone, and to assess the tolerability of combined estrogen therapy plus the Mirena IUS as a treatment option for symptomatic perimenopausal women.

The proposed pilot study is designed to test the feasibility and tolerability of the proposed regimens: Mirena alone or Mirena plus low-dose TDE in treating symptoms in perimenopausal women and to provide the preliminary data for a larger, comparative effectiveness study of optimal symptom control and provision of long term contraception for midlife women within 5 years of their final menstrual period.

Conditions: Menopausal and Other Perimenopausal Disorders
Being tested: Mirena, Estradiol, Placebo Gel

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

MirenaDrug
Also called IUD
Mirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).
EstradiolDrug
Also called TDE
Topical, .06%, Applied once daily for 50 days.
Placebo GelDrug
Also called placebo
Topical Gel, Applied once daily for 50 days, Placebo comparator.

Study groups in NCT01613131
Study group	Role	What they receive
Mirena + Estradiol Gel	Active comparator	Subjects will be assigned to use of Estradiol gel for use with Mirena. Receives: Drug: Mirena; Drug: Estradiol
Mirena + Placebo Gel	Placebo comparator	Subjects will be assigned to use of placebo gel for use with Mirena. Receives: Drug: Mirena; Drug: Placebo Gel

What is being measured

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

Hot Flashes
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Measured: Day 0
Sleep
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Measured: Day 0
Depression
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Measured: Day 0
Fatigue
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.
Measured: Day 0
Sleep
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Measured: Day 90
Sleep
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Measured: Day 140
Hot Flashes
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Measured: Day 90
Hot Flashes
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Measured: Day 140
Depression
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Measured: Day 90
Depression
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Measured: Day 140
Fatigue
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.
Measured: Day 90
Fatigue
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.
Measured: Day 140

Timeline

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

Apr 2012Jun 2014

First posted6 Jun 2012 (estimated)
Study startApr 2012
Primary completionJun 2014
Study completionJun 2014

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Menopausal and Other Perimenopausal DisordersStudies of the same condition, open and under way.
More trials run by University of Colorado, DenverThe 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 N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 39 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01613131
Sponsor's protocol ID: 11-1711
Status last verified: Oct 2015
First submitted: 4 Jun 2012
Last updated: 2 Dec 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effectiveness of Perimenopausal Hormone Therapy in Suppression of Ovulation, Stabilization of Reproductive Hormones and Symptom Control
ClinicalTrials.gov ID: NCT01613131
Acronym / sponsor ID: 11-1711
Conditions: Menopausal and Other Perimenopausal Disorders
Study type: Interventional
Recruitment status: Completed
Enrolment: 39 participants (actual)
Lead sponsor: University of Colorado, DenverUniversity, hospital or other
Collaborators: Bayer
Study start: Apr 2012
Primary completion: Jun 2014 (actual)
Study completion: Jun 2014 (actual)
First posted: 6 Jun 2012 (estimated)
Results: Posted 2 Dec 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

The Specific Aims of the present proposal are therefore as follows:

Aim 1: To test the hypothesis that low dose estrogen therapy in concert with the low doses of levonorgestrel that circulate when Mirena is used will suppress ovulation in perimenopausal women.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Mirena + Estradiol Gel	Active comparator	Drug: Mirena, Drug: EstradiolSubjects will be assigned to use of Estradiol gel for use with Mirena.
Mirena + Placebo Gel	Placebo comparator	Drug: Mirena, Drug: Placebo GelSubjects will be assigned to use of placebo gel for use with Mirena.

Who may qualify

Ages: 40 to 52 years
Sex: Female only
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (8 listed)

Age 40-52
History of regular menstrual cycles every 20-35 days in mid-reproductive life (20-35 years of age)
At least 1 period within the past 3 months
BMI less than 35 kg/m2
Presence of at least one of the following perimenopausal symptoms:

Key exclusion criteria (13 listed)

Age < 40 years
Hysterectomy or bilateral oophorectomy
Cigarette smoking
Signs or symptoms of restless leg syndrome or sleep apnea
Any chronic renal or hepatic disease that might interfere with excretion of gonadotropins or sex steroids

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
MirenaAlso: IUDMirena (levonorgestrel-releasing intrauterine system), 52 mg (20 mcg/day), 5 year duration (study duration 6 months).	Drug	Mirena + Estradiol Gel, Mirena + Placebo Gel
EstradiolAlso: TDETopical, .06%, Applied once daily for 50 days.	Drug	Mirena + Estradiol Gel
Placebo GelAlso: placeboTopical Gel, Applied once daily for 50 days, Placebo comparator.	Drug	Mirena + Placebo Gel

Primary outcome

Hot Flashes
Time frame: Day 0
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Sleep
Time frame: Day 0
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Depression
Time frame: Day 0
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Fatigue
Time frame: Day 0
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.
Sleep
Time frame: Day 90
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Sleep
Time frame: Day 140
The Pittsburgh Sleep Quality Index (PSQI) is a 19-item scale designed to measure general sleep disturbances over the previous month (sleep wake patterns, duration of sleep, sleep latency, impact of poor sleep on daytime functioning, assesses specific problems contributing to poor sleep, including pain, urination, breathing difficulty, snoring, dreams, temperature). The global score is reported and ranges from 1-21, with higher scores being indicative of poorer sleep.
Hot Flashes
Time frame: Day 90
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Hot Flashes
Time frame: Day 140
The Hot Flash Related Daily Interference Scale (HFRDIS) is a ten item scale measuring degree to which hot flashes interfere with 9 daily activities (work, social, leisure, sleep, mood, concentration, relations, sexuality, enjoyment of life, overall quality of life) over the prior week, each scored on a 10 point Likert scale. The total score is reported, and scores range from 0-100, 100 being the worst outcome.
Depression
Time frame: Day 90
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Depression
Time frame: Day 140
The Center for Epidemiologic Studies-Depression Scale (CES-D) is a 20-item scale with 4-point Likert responses indicating frequency of symptoms over past week. Scores range from 0-60, with scores >16 considered indicative of depressive symptoms.
Fatigue
Time frame: Day 90
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.
Fatigue
Time frame: Day 140
The Fatigue Severity Scale (FSS) was used to determine the degree to which night-time sleep difficulty manifested as daytime sleepiness. The FSS is a 9-item scale assessing fatigue over the past week, on a 7-point Likert scale (ranging from 1-7). It is scored by averaging the individual item scores, with higher scores indicating greater fatigue. Scores greater than or equal to 5.5 are generally indicative of insomnia with impaired daytime functioning.

Results and safety

Results posted to the registry on 2 Dec 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Mirena + Estradiol Gel	20	17
Mirena + Placebo Gel	18	13

Primary outcome: Hot Flashes

Time frame: Day 0. Mean (Standard Error). Unit: scores on a scale

Measure	Mirena + Estradiol Gel n = 20	Mirena + Placebo Gel n = 18
Value	10.3 (2.653)	7.944 (2.85)

Primary outcome: Sleep

Time frame: Day 0. Mean (Standard Error). Unit: scores on a scale

Measure	Mirena + Estradiol Gel n = 20	Mirena + Placebo Gel n = 18
Value	9.80 (1.13)	8.83 (1.01)

Primary outcome: Depression

Time frame: Day 0. Mean (Standard Error). Unit: scores on a scale

Measure	Mirena + Estradiol Gel n = 20	Mirena + Placebo Gel n = 16
Value	9.8 (1.34)	11.31 (2.27)

Population analysed: Two women in the Mirena + Placebo Gel did not provide complete data for this outcome measure; thus they were not included in the analysis for this timepoint.

Primary outcome: Fatigue

Time frame: Day 0. Mean (Standard Error). Unit: scores on a scale

Measure	Mirena + Estradiol Gel n = 20	Mirena + Placebo Gel n = 17
Value	3.38 (.32)	3.90 (.34)

Population analysed: One woman in the Mirena + Placebo Gel arm did not provide complete data for this outcome measure; thus she was not included in the analysis for this timepoint.

Adverse events

Time frame: 140 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Mirena + Estradiol Gel	0 of 20 (0%)	1 of 20 (5%)	Not reported
Mirena + Placebo Gel	0 of 18 (0%)	1 of 18 (5.6%)	Not reported

Limitations and caveats (from the sponsor): The main limitation was the sample size, which is consistent with a pilot study, and which can only inform the design of future research.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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.

Nanette Santoro, MD principal investigator

University of Colorado, Denver

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

Questions about this trial

What is this clinical trial studying?

A study testing Mirena and Estradiol in people with Menopausal and Other Perimenopausal Disorders, run by University of Colorado, Denver 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 8 inclusion and 13 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: finished, as of the sponsor's last update on 2 Dec 2015. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Dec 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Hot Flashes (time frame: Day 0). The study lists 12 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 NCT01613131.

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 2 Dec 2015.