Raloxifene in Treatment of Schizophrenia and Schizoaffective Disorder

Schizophrenia Clinical Trial

— RAL-S-01  

Official title:

A Randomized Trial Administering Raloxifene vs Placebo as add-on to Antipsychotics in Post Menopausal Patients With Schizophrenia or Schizoaffective Disorder

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01280305
• Other study ID #: SHEBA-10-8287-MW-SHEBA
• Status: Not yet recruiting
• Phase: Phase 3
• First received: January 19, 2011
• Last updated: January 19, 2011
• Start date: March 2011
• Est. completion date: March 2013

Study information

• Verified date: January 2011
• Source: Sheba Medical Center
• Contact: Mark Weiser, MD
• Phone: 972-52-666-6575
• Email: mweiser[@]netvision.net.il
• Is FDA regulated: No
• Health authority: Israel: Israeli Health Ministry Pharmaceutical Administration
• Study type: Interventional

Clinical Trial Summary

The objective of the study is to evaluate the efficacy of raloxifene compared to placebo, as add-on to anti-psychotics in the treatment of post menopausal patients with schizophrenia.

Description:

Epidemiological evidence shows a potentially protective role for estrogen in women with schizophrenia. The onset of schizophrenia is later in woman than in men, with generally a less severe course until after the menopause, when for many women, reductions in estrogen levels appear to trigger an exacerbation or illness (Hafner 2003). ERα (Estrogen receptor alpha) expression is known to be reduced in schizophrenia (Wong, Woon et al. 2010). Raloxifene is a selective estrogen receptor modulator that acts as an estrogen antagonist in breast tissue and may have agonistic actions in the brain. Several studies (Kulkarni, Riedel et al. 2001; Chua, de Izquierdo et al. 2005; Kulkarni, Gurvich et al. 2010) indicate that treatment with estrogen and raloxifene improves symptoms in females with schizophrenia, and recently they showed an improvement in PANSS score in post menopausal women with schizophrenia receiving 60-120mg/d of raloxifene compared to placebo

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 200
• Est. completion date: March 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Post menopausal females: Post menopausal defined as: Women 45 years of age and older with no vaginal bleeding for at least 2 years prior to randomization, and both serum estradiol <73 pmol/L (20 pg/mL) and FSH >30 IU/L (30 mIU/mL).

2. 45-65 years old

3. Willing and able to provide informed consent, after the nature of the study has been fully explained.

4. Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified SCID and having had at least 2 prior schizophrenic episodes, or continually ill for at least 6 months.

5. Symptoms: 4 (moderate) or above on CGI-S and 4 (moderate) score or above on two of the following four PANSS items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution, and/or a total PANSS negative symptoms score of 18.

6. Must be on 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 the dose is required and, if possible, will be stabilized on a lower dose prior to study entry.

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. Women of child bearing potential.

3. Women who have amenorrhea due to causes other than natural or surgical menopause i.e. eating disorders or exercise

4. Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning.

5. Patients treated with cholestyramine, warfarin or concurrent systemic estrogen therapy

6. Likely allergy or sensitivity to raloxifene.

7. At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.

8. 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.

9. Concurrent delirium, mental retardation, drug-induced psychosis, or history of brain trauma.

10. Patients with hypercoaguable conditions or risk of venous thrombosis.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Drug:
• raloxifene
raloxifene 60 mg bid
• placebo
Placebo bid

Locations

Country	Name	City	State
Israel	Sheba Medical Center	Ramat Gan
Romania	Clinica de Psihiatrie, Arad	Arad
Romania	Spitalul de Psihiatrie Botosani	Botosani
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"	Bucuresti
Romania	Spitalul Clinic Judetean de Urgenta Cluj	Cluj
Romania	Sp. Jud. "Prof. Dr.O. Fodor"	Cluj-Napoca
Romania	Spitalul Clinic de Psihiatrie Socola, Iasi	Iasi

Sponsors (1)

Lead Sponsor	Collaborator
Sheba Medical Center

Countries where clinical trial is conducted

Israel,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PANSS total score at the end of the trial.	PANSS will be assesed at weeks 5, 8 and end of study.	3 times	No
Secondary	PANSS,CGI-S, CGI-I, BACS and rates of drop outs before the end of the trial.	PANSS will be assessed at week 5, 8, and end of study; CGI-S, CGI-I, will be assessed at week 2, 5, 8, 12, and end of study; BACS will be assessed at week 8 and end of study.	PANSS 3 times, CGI-S and CGI-I 5 times and BACS 2 times	No