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Perimenopausal DepressionPhase 4NCT00030147

Raloxifene and Rimostil for Perimenopause-Related Depression

A Phase 4 study testing Raloxifene, Rimostil and Transdermal Estradiol in people with Perimenopausal Depression and Depression, run by National Institute of Mental Health (NIMH) 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

The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression. Perimenopause-related mood disorders cause significant distress to a large number of women; the demand for effective therapies to treat these mood disorders is considerable. Read more about this study

Who is it for?
Ages 40 to 60 years, women only
Conditions the study is for
Perimenopausal Depression, Depression
What is being tested?
Raloxifene, Rimostil and Transdermal Estradiol
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
65 participants
Where
1 siteUnited States
Study dates
Feb 2002to Jun 2015
Phase
Phase 4
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 60 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • Subjects for this study will meet the following criteria:
  • Self-report of the onset of depression associated with menstrual cycle irregularity or amenorrhea;
  • A current episode of minor (meeting 3-4 criterion symptoms) or major depression (of moderate severity or less on the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (SCID) severity scale and not meeting DSM-IV criteria symptom 9 (suicide)) as determined by the administration of the minor depression module of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version (SADS-L). Additionally, to ensure that subjects meet a minimum threshold for severity of depression, subjects will have scores greater than or equal to 10 on either the Beck Depression Inventory (BDI) or the Center for Epidemiologic Studies - Depression (CES-D) Scale during at least three of the four clinic visits during the two month screening phase, as well as a 17 item Hamilton Depression score greater than or equal to 10. Subjects will be excluded if they meet any of the following criteria: major depression of greater than moderate severity, DSM-IV criteria # 9 (suicide), or anyone requiring immediate treatment after clinical assessment or functional impairment ratings of five or six for more than seven consecutive days on daily ratings;
  • Evidence of perimenopausal reproductive status;
  • Age 40 to 60;
  • No prior hormonal therapy for the treatment of perimenopause-related mood or physical symptoms within the last six months;
  • No history of psychiatric illness during the two years prior to the reported onset of the current episode of depression;
  • In good medical health, and not taking any medication or dietary and herbal supplements on a regular basis (with the exception of multivitamins and calcium supplements).

Who cannot join

  • The following conditions will constitute contraindications to treatment and will preclude a subject s participation in this protocol:
  • 1) Severe major depression with any of the following:
  • positive (threshold) response to SCID major depression section item # 9, suicidal ideation;
  • anyone requiring immediate treatment after clinical assessment;
  • severity ratings greater than moderate on the SCID IV interview;
  • functional impairment ratings of five or six for more than seven consecutive days on daily ratings.
Show all 22Show fewer
  • 2) Current treatment with antidepressant medications. Our main concern is to exclude subjects taking medications that would treat or precipitate depression or adversely interact with reproductive hormones, phytoestrogens (e.g., anticoagulants), or SERMs. Thus, we wish to exclude only women receiving psychotropic medications, medications that have been reported to induce a change in mood or behavior, hormone replacement therapy, oral contraceptive agents, or medications that may have a potential adverse interaction with the compounds employed in this study.
  • 3) History of psychiatric illness during the two years before the reported onset of the current episode of depression.
  • 4) History of ischemic cardiac disease, pulmonary embolism, retinal thrombosis, or thrombophlebitis; any subject with risk factors for thrombo-embolic phenomena including cigarette smokers; varicose veins, patients with prolonged periods of immobilization (including prolonged travel), and active heart disease. The literature suggests that although both smoking and hormone replacement/oral contraceptives have associated risks of thromboembolic phenomena and cardiovascular events, these individual risks do not become significantly greater when combined until greater than 10 cigarettes a day are consumed. Thus we wish to exclude only subjects for this study who smoke greater than 10 cigarettes per day.
  • 5) Renal disease, asthma.
  • 6) Hepatic dysfunction.
  • 7) Women with a history of carcinoma of the breast, or any women with a family history of the following: premenopausal breast cancer or bilateral breast cancer in a first degree relative; multiple family members (greater than three relatives) with postmenopausal breast cancer.
  • 8) Women with a history of uterine cancer, endometriosis, ill-defined pelvic lesions, particularly undiagnosed ovarian enlargement, undiagnosed vaginal bleeding.
  • 9) Patients with a known hypersensitivity to raloxifene, phytoestrogens (including Rimostil, isoflavones, genistein, daidzein, red clover extract and soy-related compounds), estradiol, Alora, medroxyprogesterone acetate, or the excipients (inactive compounds) contained within these medications including: Rimostil -tocopherols, cellulose, calcium hydrogen phosphate, magnesium stearate, silica-colloidal anhydrous; Provera - calcium stearate, corn starch, lactose, mineral oil, sorbic acid, sucrose, talc; Alora - sorbitan monooleate, acrylic adhesive; Evista - anhydrous lactose, carnauba wax, crospovidone, Federal Food, Drug, and Cosmetic Act (FD\& C) blue # 2 aluminum lake, hydroxypropyl methylcellulose, lactose monohydrate, magnesium stearate, modified pharmaceutical glaze, polyethylene glycol, polysorbate 80, povidone, and titanium dioxide.
  • 10) Pregnant women.
  • 11) Porphyria.
  • 12) Diabetes mellitus.
  • 13) Cholecystitis or pancreatitis.
  • 14) History of cerebrovascular disease (stroke), epilepsy, hypertension, hypercalcemia.
  • 15) Recurrent migraine headaches.
  • 16) Malignant melanoma.
  • 17) History of familial hyperlipoproteinemia.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: The Efficacy of Phytoestrogens and Selective Estrogen Receptor Modulators in Perimenopause-Related Depression

The purpose of this study is to evaluate the effectiveness of the drugs raloxifene and rimostil in treating perimenopause-related depression.

Perimenopause-related mood disorders cause significant distress to a large number of women; the demand for effective therapies to treat these mood disorders is considerable. Estradiol replacement therapy (ERT) has demonstrated efficacy in treating perimenopause-related depression. Unfortunately, there are long-term risks associated with ERT. Selective estrogen receptor modulators (SERMS), such as raloxifene, and phytoestrogens, such as rimostil, have estrogen-like properties and may offer a safer alternative to ERT. The effect of SERMS and phytoestrogens on mood and cognitive functioning need to be examined in women with perimenopause-related depression.

Participants in this study will undergo a medical history, physical examination, electrocardiogram (EKG), and blood and urine tests. They will then be randomly assigned to receive one of four treatments for 8 weeks: raloxifene pills plus a placebo (an inactive substance) skin patch, rimostil pills plus placebo skin patch, estradiol skin patch plus placebo pills, or placebo patch plus placebo pills. Participants will have clinic visits every 2 weeks. During the visits, blood will be drawn and participants will meet with staff members and complete symptom self-rating scales. A urine and blood sample will be collected at the beginning and end of the study. At the end of the study, participants who received placebo or whose study medication was ineffective will be offered treatment with standard antidepressant medications for 8 weeks. Non-menstruating women will receive progesterone for 10 days to induce menstrual bleeding and shedding of the inner layer of the uterus, which may have been stimulated by the study medications.

Read the detailed description

Perimenopause-related mood disorders cause significant distress to a potentially large number of women. The demand for effective therapeutic alternatives to estrogen for treating these mood disorders is considerable, as is the need to define clinical or biologic markers that may predict successful response of mood disturbances to phytoestrogens or selective estrogen receptor modulators (SERMs). Further, the study of potential biological mechanisms underlying both perimenopause-related mood disorders and their response to treatment may offer the possibility of uncovering some etiopathogenic mechanisms involved in these and related mood disorders.

Results of protocol # 90-M-0077 demonstrated the therapeutic efficacy of estradiol therapy (ET) in perimenopausal depression, independent of its effects on vasomotor symptoms. Nevertheless, the long term risks of ET to endometrial and breast tissues continue to deter many women from its use. Recently, selective estrogen receptor modulators (SERMs) and phytoestrogens (plant-derived estrogen-like compounds) have become available and are reported to display both tissue-specific profiles of estrogen agonist and antagonist actions and differential affinities for the two forms of estrogen receptor. For many women, these novel compounds would represent a safer alternative to ET for the prevention of osteoporosis and the treatment of menopausal symptoms. However, the effects of SERMs and phytoestrogens on mood and cognitive function in perimenopausal women remain undetermined.

In this protocol we wish both to investigate the effects of SERMs and phytoestrogens on mood and cognition under placebo controlled conditions and to compare these effects with estradiol therapy. This protocol will address the following questions: 1) Do selective estrogen receptor modulators or phytoestrogens improve mood and cognition in perimenopausal depressed women? 2) Are the mood and cognitive effects of SERMs and phytoestrogens comparable to those of ET? and 3) Do selective estrogen receptor modulators and phytoestrogens improve measures of bone metabolism in perimenopausal depressed women?

Being tested
Raloxifene, Rimostil, Transdermal Estradiol, Placebo skin patch and placebo tablets
Keywords
Gonadal Steroids, Estrogen Receptor, Mood Disorders, Perimenopause, Estradiol, Depression, Estrogen Response Element, Perimenopausal, Perimenopausal Depression
Medical subject headings
Depression, Mood Disorders

What participants receive

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

  • RaloxifeneDrug

    Also called Evista

    60 mg a day orally administered

  • RimostilDrug

    1000 mg twice a day administered orally

  • Transdermal EstradiolDrug

    Also called Alora

    100 microgram per day transdermal estradiol

  • Placebo skin patch and placebo tabletsDrug

    matched placebo skin patch to transdermal estradiol and matched tablets to either Raloxifene or Rimostil

Study groups in NCT00030147
Study groupRoleWhat they receive
RaloxifeneExperimentalRaloxifene (Evista) 60 mg per day and placebo skin patch for eight weeks
Receives: Drug: Raloxifene
RimostilExperimentalRimostil (phytoestrogen) 1000 mg twice a day and placebo skin patch for eight weeks
Receives: Drug: Rimostil
Transdermal estradiolActive comparator17-beta estradiol 100 micrograms a day by skin patch and placebo tablets for eight weeks
Receives: Drug: Transdermal Estradiol
PlaceboPlacebo comparatorPlacebo skin patch and placebo tablets for eight weeks.
Receives: Drug: Placebo skin patch and placebo tablets

What is being measured

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

  1. Center for Epidemiologic Studies-Depression Scale (CES-D)

    Center for Epidemiologic Studies-Depression Scale (CES-D) cutoff scores are typically used as a screen to identify clinically significant depression; a cutoff score of greater than 16 has been shown to correlate with clinically significant depression. In addition, a score between 8 and 15 has been used to define subsyndromal depression. The possible range of scores is zero to 60, with the higher scores indicating more symptoms, weighted by frequency of occurrence during the past week.

    Measured: Baseline

  2. Center for Epidemiologic Studies-Depression Scale (CES-D)

    Center for Epidemiologic Studies-Depression Scale (CES-D) cutoff scores are typically used as a screen to identify clinically significant depression; a cutoff score of greater than 16 has been shown to correlate with clinically significant depression. In addition, a score between 8 and 15 has been used to define subsyndromal depression. The possible range of scores is zero to 60, with the higher scores indicating more symptoms, weighted by frequency of occurrence during the past week.

    Measured: Week 8

Timeline

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

  1. First posted7 Feb 2002 (estimated)
  2. Study startFeb 2002
  3. Primary completionJun 2015
  4. Study completionJun 2015

Resources

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
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
65 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00030147
Sponsor's protocol ID
020120
Other IDs
ZIAMH002537-26, 02-M-0120
Status last verified
Jul 2016
First submitted
6 Feb 2002
Last updated
5 Sep 2016
Data monitoring committee
No
Individual data sharing
No

Publications

  • Schmidt PJ, Wei SM, Martinez PE, Dor RRB, Guerrieri GM, Palladino PP, Harsh VL, Li HJ, Wakim P, Nieman LK, Rubinow DR. The short-term effects of estradiol, raloxifene, and a phytoestrogen in women with perimenopausal depression. Menopause. 2021 Jan 15;28(4):369-383. doi: 10.1097/GME.0000000000001724.

    PubMed 33470755

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Raloxifene, Rimostil and Transdermal Estradiol in people with Perimenopausal Depression and Depression, run by National Institute of Mental Health (NIMH) 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 22 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 5 Sep 2016. 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.

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?

Yes. Results are posted in the registry (first posted 5 Sep 2016). 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?

Center for Epidemiologic Studies-Depression Scale (CES-D) (time frame: Baseline). The study lists 2 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 NCT00030147, which also lists 1 linked publication.

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 Sep 2016.

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