Estradiol as add-on to Antipsychotics (EST-S-02)

May 21, 2020 updated by: Tangent Data

A Randomized Trial Administering Estradiol Patch vs. Placebo Patch as add-on to Antipsychotics in Female Patients Above the Age of 38 With Schizophrenia, Schizoaffective or Schizophreniform Disorder

The objective of the study is to evaluate the efficacy of Estradiol patch compared to placebo, as add-on to anti-psychotics in the treatment of women 38 and older with schizophrenia, schizoaffective or schizophreniform disorder.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Several lines of evidence suggest that estrogen affects the course of schizophrenia. The onset of schizophrenia is 2-4 years later in women than in men, and women have a lower incidence of schizophrenia until menopause, after which women have an increased incidence, so that the lifetime prevalence is similar in both genders. Women are more likely to have their first schizophrenic episode during an estradiol trough in the menstrual cycle. These gender differences in the natural course of schizophrenia are well replicated and provide a major lead to understanding and treating the illness, and have led to several randomized controlled trials administering oral estradiol to patients with schizophrenia. Studies on transdermal estradiol have been more encouraging, and four RCTs, have shown that estradiol patches are efficacious in treating schizophrenia The most recent study was performed our group and showed that overall estradiol patches were efficacious with an effect size of 0.41 for total PANSS, with significant improvements in PANSS positive, negative and general-psychopathology scores. Post hoc analyses showed that the improvements in symptoms were found almost exclusively in women who were 38 and older, in whom the effect of estrogen patches vs placebo reached an effect size of 0.58 for PANSS total.

The currently proposed study is based on the post-hoc finding of improvement in participants aged 38 and above, and we will a-priori recruit women with schizophrenia 38 and above, in order to test the efficacy of 200 µg estradiol patches vs placebo in these woman.

Study Type

Interventional

Enrollment (Anticipated)

100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Moldova, Republic of
      • Chisinau, Moldova, Republic of, MD2072
        • Recruiting
        • Centrul Comunitar de Sănătate Mintală Botanica
        • Contact:
          • Nicolae Cebotari, M.D.
          • Phone Number: +373 6927 4593

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

38 years to 48 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  1. Female above 38, up to 45 years of age, inclusive
  2. Willing and able to provide informed consent, after the nature of the study has been fully explained
  3. Current DSM-V diagnosis of schizophrenia, schizoaffective or schizophreniform disorder as confirmed by modified SCID.
  4. Total PANSS score > 70 and (PANSS positive subscale >15 and/or PANSS negative subscale >15)
  5. Must be on a stable dose of any antipsychotic drug, for at least 2 weeks prior to the baseline visit, at doses within the PORT criteria, whenever possible. Patients receiving higher doses will have their records reviewed to ensure that their dose is required and, if possible, will be stabilized on a lower dose prior to study entry.
  6. Patients who are physically and endocrinologically healthy,
  7. Not menopausal as assessed by asking patients if they are menstruating
  8. Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission

Exclusion Criteria:

  1. Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
  2. Pregnant or breast-feeding
  3. Women who are menopausal.
  4. Patients treated with oral estrogen preparations containing estradiol greater than 30 mcg.
  5. Women who have known severe abnormalities in the hypothalamo-pituitary gonadal axis, thyroid disorders, severe medical conditions and disorders that would contraindicate estrogen use (breast cancer, migraine with aura or stroke)
  6. History of endometrial cancer or breast cancer, history of breast or uterine cancer, no history of 1st and 2nd grade family with breast or uterine cancer, vaginal bleeding between periods.
  7. Likely allergy or sensitivity to estradiol.
  8. Schizoaffective disorder in the manic phase.
  9. At significant risk of committing suicide, or in the opinion of the Investigator, currently at imminent risk of suicide or harming others.
  10. Patients with a current DSM-V substance or alcohol abuse. Patients with a history of and/or current recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
  11. Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
  12. Patients receiving phenobarbital, phenytoin, carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and nelfinavir,or Hypericum perforatum.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo Comparator
Placebo
Drug: Placebo
2 transdermal patches to be changed twice a week for the duration of 16 weeks
Other Names:
  • trans dermal patches
Active Comparator: Active Comparator
Estradiol 200µg
Drug: Estradiol
2 transdermal patches to be changed twice a week for the duration of 16 weeks
Other Names:
  • trans dermal patches

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in total PANSS scores at the end of the trial
Time Frame: Change from Baseline at 16 weeks
The Positive and Negative Syndrome Scale (PANSS) is a well validated, standardized method of evaluating and monitoring psychotic symptoms. The PANSS assesses: positive (hallucinations, delusions, thought disorder), negative (blunted affect, abstract thinking and general symptomatology. The positive and negative subscale each consist of 7 items rated from 1(absent) - 7(extreme) with a minimum score = 7, maximum score = 49. The general subscale consists of 16 items with a minimum score = 16, maximum score = 112. A Total PANSS score (positive+ negative + general scores) has a minimum of 30 and maximum of 210. Higher scores represent more severity in symptoms.
Change from Baseline at 16 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of drop outs before the end of the trial
Time Frame: through study completion, an average of 1 year
To evaluate the rate of drop outs
through study completion, an average of 1 year
Positive and Negative Syndrome Scale (PANSS) and general psychopathology scales
Time Frame: through study, 16 weeks
To evaluate the effects of Estradiol on Positive and Negative Syndrome Scale (PANSS)
through study, 16 weeks
Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I),
Time Frame: through study, 16 weeks
To evaluate the effects of Estradiol vs Placebo on Clinical Global Impression
through study, 16 weeks
Montgomery-Asberg Depression Rating Scale
Time Frame: through study, 16 weeks
To evaluate the effects of Estradiol on depressive symptoms
through study, 16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tangent Data

Collaborators

Stanley Medical Research Institute
MediStat Ltd.
PCI pharma services (formerly BIOTEC SERVICES INTERNATIONAL LIMITED)
S.C. IMUNOTEHNOMED S.R.L.
Tangent Data Srl

Investigators

  • Principal Investigator: Mark Weiser, M.D., Sheba Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 2, 2019

Primary Completion (Anticipated)

October 15, 2020

Study Completion (Anticipated)

November 1, 2020

Study Registration Dates

First Submitted

September 16, 2019

First Submitted That Met QC Criteria

September 17, 2019

First Posted (Actual)

September 18, 2019

Study Record Updates

Last Update Posted (Actual)

May 26, 2020

Last Update Submitted That Met QC Criteria

May 21, 2020

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EST-S-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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