Perimenopausal DepressionPhase 4NCT01368068
Investigation of Tibolone and Escitalopram in Perimenopausal Depression
A Phase 4 study testing Tibolone, Escitalopram and Natvia in people with Perimenopausal Depression, run by The Alfred at 1 site in Australia.
Trial summary
Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the… Read more about this study
- Who is it for?
- Ages 45 to 55 years, women only
- Conditions the study is for
- Perimenopausal Depression
- What is being tested?
- Tibolone, Escitalopram and Natvia
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2012to Jul 2012
- Phase
- Phase 4
- 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 45 to 55 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Females who are currently physically well and between 45 and 55 years of age
- Current DSM-IV diagnosis of depression disorder
- Able to give informed consent
- Perimenopausal as determined by symptom profile on the Stages of Reproductive Aging Workshop and gonadal hormonal profile
Who cannot join
- Known abnormalities in the hypothalamic-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, breast pathology, undiagnosed vaginal bleeding or abnormal Pap smear results in the previous 2 years.
- Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; or the presence of illness causing immobilisation.
- Patients receiving treatment for depression including antidepressant medications, electroconvulsive therapy (ECT) / Transcranial Magnetic Stimulation (TMS), formal psychotherapy or counselling, within the past 6 months
- Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.
- Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.
- Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet
Show all 9Show fewer
- Pregnancy / Lactation
- Smoking cigarettes and other nicotine products.
- illicit drug use and more than 3 standard drinks per day
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-Blind Randomised Investigation of Tibolone or Escitalopram in First Onset Perimenopausal Depression
Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes.
Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment.
To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action)compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.
Read the detailed description
All women experience menopause and a significant number suffer from ongoing, severe depression beginning with the major hormone fluctuations in this middle stage of life. The number of women experiencing menopause related major depression and the impact of this depression on the woman's life, work and her family are grossly underestimated. We propose to conduct a clinical trial of a new hormone treatment for women with severe depression related to menopause, compared with standard antidepressant medication.
Longitudinal epidemiological studies have shown that many women experience significant physical and psychological changes as they approach menopause and for a long time following. Vasomotor symptoms (such as hot flushes, night sweats), sleep disturbances and changes in libido are common, and impact significantly on the quality of life, social and personal well-being. However, the major reason that many women seek help from menopause clinics or their doctors, is for depression and anxiety symptoms.
Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes.
Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment.
To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action) compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.
- Conditions
- Perimenopausal Depression
- Being tested
- Tibolone, Escitalopram, Natvia
- Keywords
- Perimenopause, Depression
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiboloneDrug
Also called Livial
2.5mg/oral/daily
EscitalopramDrug
Also called Lexapro
10mg/oral/daily
NatviaDrug
Also called Natvia Natural Sweetener
serving size: 0.09g per tablet
| Study group | Role | What they receive |
|---|---|---|
| Tibolone | Experimental | Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial. Receives: Drug: Tibolone |
| Escitalopram | Active comparator | 10mg of escitalopram will be taken by participants daily for the duration of the 12 week trial period. Receives: Drug: Escitalopram |
| Placebo | Placebo comparator | Placebo arm containing sweetener has been approved and will be used as placebo arm. Receives: Drug: Natvia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery and Asberg Depression Rating Scale
A 10-item clinician rated scale validated to be most strongly sensitive to change in depression associated with treatment. This scale will be used to measure change in depression associated with treatment at weeks 2, 4, 8 and 12 compared to baseline.
Measured: Baseline, then at weeks 2, 4, 8 and 12.
Secondary outcomes (4)
Short Form-36 Health Survey (SF-36)
A 36 item self report measure that assesses: physical health and bodily pain; vitality, social functioning; role limitations due to emotional problems; and mental health. This scale will be used to assess the changes to various domains of self-reported health from baseline compared to visits at baseline and week 12.
Measured: Baseline and 12
Pittsburgh Sleep Quality Index
A valid and reliable 19-item self report index measuring sleep quality, latency, duration, disturbances, and daytime dysfunction. This scale will be used to measure different domains of sleep quality at visits occurring at week baseline and week 12 compared to initial baseline measurement.
Measured: Baseline and 12.
Adverse Symptoms Checklist
A 22 item checklist of general adverse symptoms experienced. This scale will be used to measure adverse symptoms experienced by participants at weeks 2, 4, 8 and 12 compared to baseline.
Measured: Weeks 2, 4, 8 and 12
Beck Depression Inventory Scale
A subjective rating scale that compliments the MADRS and will be used at baseline and week 12 visits throughout the study.
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2011 (estimated)
- Study startJul 2012
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: Difficulty in recruiting
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Perimenopausal DepressionStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Alfred
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jayashri Kulkarni, Professor, The Alfred
- Investigators
- Jayashri Kulkarni, PhD,FRANZP, Principal investigator, Monash Alfred Psychiatry Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01368068
- Sponsor's protocol ID
- 161/11
- Status last verified
- Mar 2015
- First submitted
- 3 Jun 2011
- Last updated
- 31 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Randomised Investigation of Tibolone or Escitalopram in First Onset Perimenopausal Depression
- ClinicalTrials.gov ID
- NCT01368068
- Acronym / sponsor ID
- 161/11
- Conditions
- Perimenopausal Depression
- Keywords
- Perimenopause, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Difficulty in recruiting
- Enrolment
- 2 participants (actual)
- Lead sponsor
- The AlfredUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 7 Jun 2011 (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.
Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes.
Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment.
To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action)compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.
Detailed description
All women experience menopause and a significant number suffer from ongoing, severe depression beginning with the major hormone fluctuations in this middle stage of life. The number of women experiencing menopause related major depression and the impact of this depression on the woman's life, work and her family are grossly underestimated. We propose to conduct a clinical trial of a new hormone treatment for women with severe depression related to menopause, compared with standard antidepressant medication.
Longitudinal epidemiological studies have shown that many women experience significant physical and psychological changes as they approach menopause and for a long time following. Vasomotor symptoms (such as hot flushes, night sweats), sleep disturbances and changes in libido are common, and impact significantly on the quality of life, social and personal well-being. However, the major reason that many women seek help from menopause clinics or their doctors, is for depression and anxiety symptoms.
Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes.
Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment.
To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action) compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Tibolone | Experimental | Drug: TiboloneSubjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial. |
| Escitalopram | Active comparator | Drug: Escitalopram10mg of escitalopram will be taken by participants daily for the duration of the 12 week trial period. |
| Placebo | Placebo comparator | Drug: NatviaPlacebo arm containing sweetener has been approved and will be used as placebo arm. |
Who may qualify
- Ages
- 45 to 55 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Females who are currently physically well and between 45 and 55 years of age
- Current DSM-IV diagnosis of depression disorder
- Able to give informed consent
- Perimenopausal as determined by symptom profile on the Stages of Reproductive Aging Workshop and gonadal hormonal profile
Key exclusion criteria (9 listed)
- Known abnormalities in the hypothalamic-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, breast pathology, undiagnosed vaginal bleeding or abnormal Pap smear results in the previous 2 years.
- Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; or the presence of illness causing immobilisation.
- Patients receiving treatment for depression including antidepressant medications, electroconvulsive therapy (ECT) / Transcranial Magnetic Stimulation (TMS), formal psychotherapy or counselling, within the past 6 months
- Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.
- Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.
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 |
|---|---|---|
| TiboloneAlso: Livial2.5mg/oral/daily | Drug | Tibolone |
| EscitalopramAlso: Lexapro10mg/oral/daily | Drug | Escitalopram |
| NatviaAlso: Natvia Natural Sweetenerserving size: 0.09g per tablet | Drug | Placebo |
Primary outcome
Montgomery and Asberg Depression Rating Scale
Time frame: Baseline, then at weeks 2, 4, 8 and 12.
A 10-item clinician rated scale validated to be most strongly sensitive to change in depression associated with treatment. This scale will be used to measure change in depression associated with treatment at weeks 2, 4, 8 and 12 compared to baseline.
4 secondary outcomes
Short Form-36 Health Survey (SF-36)
Time frame: Baseline and 12
Pittsburgh Sleep Quality Index
Time frame: Baseline and 12.
Adverse Symptoms Checklist
Time frame: Weeks 2, 4, 8 and 12
Beck Depression Inventory Scale
Time frame: Baseline and week 12
Results and safety
The study was stopped early (reason given: Difficulty in recruiting). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2015.
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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.
Jayashri Kulkarni, PhD,FRANZP principal investigator
Monash Alfred Psychiatry Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tibolone, Escitalopram and Natvia in people with Perimenopausal Depression, run by The Alfred at 1 site in Australia.
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 9 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: stopped early, as of the sponsor's last update on 31 Mar 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 Australia. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 stopped early (reason given: Difficulty in recruiting). 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?
Montgomery and Asberg Depression Rating Scale (time frame: Baseline, then at weeks 2, 4, 8 and 12.). 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 31 Mar 2015.