Estradiol Patch as add-on to Antipsychotics in Patients With Schizophrenia, Schizoaffective or Schizophreniform Disorder

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

To evaluate the effects of Estradiol patches vs placebo patches as add-on to antipsychotics on psychometric performance in patients with schizophrenia, schizoaffective or schizophreniform disorder

Study Overview

• Status: Completed
• Conditions: Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorders
• Intervention / Treatment: Drug: Estradiol; Device: Placebo

Detailed Description

Estradiol has been shown to be an effective adjunctive treatment for schizophrenia. The estradiol hypothesis was tested in a randomized-controlled trial in which estradiol was given to women with schizophrenia, schizoaffective or schizophreniform disorder aged 18 to 45 - Kulkarni 2014. In that 3 arms trial, Kulkarni administered transdermal 100 µg estradiol/200 µg estradiol/ placebo to patients receiving anti-psychotics and reported reductions in PANSS positive, general and total symptoms in both estradiol patients' groups compared with the placebo group. Patients receiving 200 µg experienced greater improvement, specifically in the PANSS positive subscale, the effect size was 0.44.

The objective of this study is to attempt to confirm Kulkarni's trial in a large-scale trial. This proposed study is a 2-arm study, in which patients will be randomized to either 200 µg estradiol or placebo in order to test the effectiveness of estradiol on women of childbearing age with schizophrenia, schizoaffective or schizophreniform disorder for a limited period of 56 days.

• Study Type: Interventional
• Enrollment (Actual): 209
• Phase: Phase 3

Contacts and Locations

Study Locations

• Moldova, Republic of
  • Chisinau
    • Codru, Chisinau, Moldova, Republic of, 2011
      • Clinical Psychiatric Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Female, 18-45 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-IV-TR diagnosis of schizophrenia, schizoaffective or schizophreniform disorder as confirmed by modified SCID.
4. Total PANSS score > 60 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 insure 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. 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, vaginal bleeding between periods, untreated endometrial hyperplasia, previous or present thrombembolism, known thrombophilic disorders, abnormal liver function tests, porphyria.
7. History of 1st and 2nd grade family with breast or uterine cancer,
8. Likely allergy or sensitivity to estradiol.
9. Schizoaffective disorder in the manic phase.
10. At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
11. Patients with a current DSM-IV 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.
12. Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
13. Patients receiving phenobarbital, phenytoin, carbamazepine, rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and nelfinavir,or Hypericum perforatum

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A Estradiol; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks	Drug: Estradiol; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks.; Other Names: trans dermal patches; Device: Placebo; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks.; Other Names: trans dermal patches
Placebo Comparator: B Placebo; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks	Drug: Estradiol; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks.; Other Names: trans dermal patches; Device: Placebo; 2 trans dermal patches to be changed twice a week for the duration of 8 weeks.; Other Names: trans dermal patches

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS positive subscale at the end of the trial	To evaluate the effects of Estradiol on Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS total, negative and general psychopathology scales	To evaluate the effects of Estradiol on Positive and Negative Syndrome Scale for Schizophrenia (PANSS)	8 weeks
Clinical Global Impression Scale-Severity (CGI-S) and Global Impression Scale-Improvement (CGI-I)	To evaluate the effects of Estradiol on Clinical Global Impression	8 weeks
Brief Assessment of Cognition in Schizophrenia (BACS),	To evaluate the effects of Estradiol on cognition	8 weeks
Montgomery-Asberg Depression Rating Scale	To evaluate the effects of Estradiol on depressive symptoms	8 weeks
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

Collaborators and Investigators

• Sponsor: Tangent Data
• Collaborators: Stanley Medical Research Institute
• Investigators: Study Director: Paull G Radu, M.D., Tangent Data

Publications and helpful links

General Publications

• Weiser M, Levi L, Zamora D, Biegon A, SanGiovanni JP, Davidson M, Burshtein S, Gonen I, Radu P, Slobozean Pavalache K, Nastas I, Hemi R, Ryan T, Davis JM. Effect of Adjunctive Estradiol on Schizophrenia Among Women of Childbearing Age: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Oct 1;76(10):1009-1017. doi: 10.1001/jamapsychiatry.2019.1842.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2015
• Primary Completion (Actual): July 29, 2016
• Study Completion (Actual): July 29, 2016

Study Registration Dates

• First Submitted: February 13, 2019
• First Submitted That Met QC Criteria: February 19, 2019
• First Posted (Actual): February 20, 2019

Study Record Updates

• Last Update Posted (Actual): May 22, 2020
• Last Update Submitted That Met QC Criteria: May 20, 2020
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens; Estradiol
• Other Study ID Numbers: EST-S-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No