EST-S-02: Estradiol as add-on to Antipsychotics

• Sponsor: Tangent Data (Other)
• Overall Status: Unknown status
• CT.gov ID: NCT04093518
• Collaborator: Stanley Medical Research Institute (Other), MediStat Ltd. (Other), PCI pharma services (formerly BIOTEC SERVICES INTERNATIONAL LIMITED) (Other), S.C. IMUNOTEHNOMED S.R.L. (Other), Tangent Data Srl (Other)
• Enrollment: 100
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 11
• Patients Per Site Per Month: 9.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorders	Drug: Estradiol; Drug: Placebo	Phase 3

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized, add-on to anti-psychotics, double blind, placebo-controlled, parallel group clinical trialRandomized, add-on to anti-psychotics, double blind, placebo-controlled, parallel group clinical trial
• Masking: Triple (Participant, Care Provider, Investigator)
• Masking Description: Triple
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Dec 2, 2019
• Anticipated Primary Completion Date: Oct 15, 2020
• Anticipated Study Completion Date: Nov 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
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
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

Outcome Measures

Primary Outcome Measures

1. Change in total PANSS scores at the end of the trial [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.

Secondary Outcome Measures

1. Positive and Negative Syndrome Scale (PANSS) and general psychopathology scales [through study, 16 weeks]

   To evaluate the effects of Estradiol on Positive and Negative Syndrome Scale (PANSS)

2. Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I), [through study, 16 weeks]

   To evaluate the effects of Estradiol vs Placebo on Clinical Global Impression

3. Montgomery-Asberg Depression Rating Scale [through study, 16 weeks]

   To evaluate the effects of Estradiol on depressive symptoms

4. Rates of drop outs before the end of the trial [through study completion, an average of 1 year]

   To evaluate the rate of drop outs

Eligibility Criteria

Criteria

• Ages Eligible for Study: 38 Years to 48 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

1. 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.

2. Patients who are physically and endocrinologically healthy,

3. Not menopausal as assessed by asking patients if they are menstruating

4. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centrul Comunitar de Sănătate Mintală Botanica	Chisinau		Moldova, Republic of	MD2072

Sponsors and Collaborators

• Tangent Data
• 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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tangent Data
• ClinicalTrials.gov Identifier: NCT04093518
• Other Study ID Numbers: EST-S-02
• First Posted: Sep 18, 2019
• Last Update Posted: May 26, 2020
• Last Verified: Sep 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Disease; Schizophrenia; Psychotic Disorders; Estradiol

Study Results

No Results Posted as of May 26, 2020