Estradiol as add-on to Antipsychotics

Schizophrenia Clinical Trial

— EST-S-02  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04093518
• Other study ID #: EST-S-02
• Status: Recruiting
• Phase: Phase 3
• Start date: December 2, 2019
• Est. completion date: November 1, 2020

Study information

• Verified date: September 2019
• Source: Tangent Data
• Contact: Paull G Radu, M.D.
• Phone: +407 2323 4545
• Email: paull.radu[@]tangentdata.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: November 1, 2020
• Est. primary completion date: October 15, 2020
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 38 Years to 48 Years

Eligibility

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.

Related Conditions & MeSH terms

• Disease
• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia
• Schizophreniform Disorders

Intervention

Drug:
• Estradiol
2 transdermal patches to be changed twice a week for the duration of 16 weeks
• Placebo
2 transdermal patches to be changed twice a week for the duration of 16 weeks

Locations

Country	Name	City	State
Moldova, Republic of	Centrul Comunitar de Sanatate Mintala Botanica	Chisinau

Sponsors (6)

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

Country where clinical trial is conducted

Moldova, Republic of, 

References & Publications (17)

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van der Werf M, Hanssen M, Köhler S, Verkaaik M, Verhey FR; RISE Investigators, van Winkel R, van Os J, Allardyce J. Systematic review and collaborative recalculation of 133,693 incident cases of schizophrenia. Psychol Med. 2014 Jan;44(1):9-16. doi: 10.10 — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in total PANSS scores at the end of the trial	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	Positive and Negative Syndrome Scale (PANSS) and general psychopathology scales	To evaluate the effects of Estradiol on Positive and Negative Syndrome Scale (PANSS)	through study, 16 weeks
Secondary	Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I),	To evaluate the effects of Estradiol vs Placebo on Clinical Global Impression	through study, 16 weeks
Secondary	Montgomery-Asberg Depression Rating Scale	To evaluate the effects of Estradiol on depressive symptoms	through study, 16 weeks
Secondary	Rates of drop outs before the end of the trial	To evaluate the rate of drop outs	through study completion, an average of 1 year