Raloxifene in Treatment of Schizophrenia and Schizoaffective Disorder (RAL-S-01)

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

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.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia; Schizoaffective Disorder
• Intervention / Treatment: Drug: raloxifene; Drug: placebo

Detailed 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

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mark Weiser, MD; Phone Number: 972-52-666-6575; Email: mweiser@netvision.net.il

Study Locations

• Israel
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center
    • Contact: Mark Weiser, MD; Phone Number: 972-52-666-6575; Email: mweiser@netvision.net.il
    • Principal Investigator: Mark Weiser, MD
• Romania
  • Arad, Romania
    • Clinica de Psihiatrie, Arad
    • Contact: Delia Podea, MD; Phone Number: 0722 583 757; Email: deliapodea@gmail.com
    • Principal Investigator: Delia Podea, MD
  • Botosani, Romania
    • Spitalul de Psihiatrie Botosani
  • Bucuresti, Romania
    • Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"
    • Contact: Valentin Matei, MD; Phone Number: 0723 640 918; Email: petcu_camelia@yahoo.com
    • Principal Investigator: Valentin Matei, MD
  • Cluj, Romania
    • Spitalul Clinic Judetean de Urgenta Cluj
    • Contact: Ioana-Valentina Miclutia, MD; Phone Number: 0722 796 067; Email: ioanamiclu@yahoo.com
    • Principal Investigator: Ioana-Valentina Miclutia, MD
  • Cluj-Napoca, Romania
    • Sp. Jud. "Prof. Dr.O. Fodor"
    • Contact: Mircea-Alexandru Birt, MD; Phone Number: 0721 012 220; Email: mirceabirt@yahoo.com
    • Principal Investigator: Mircea-Alexandru Birt, MD
  • Iasi, Romania
    • Spitalul Clinic de Psihiatrie Socola, Iasi
    • Contact: Serban Turliuc, MD; Phone Number: 0745 203 002; Email: serban_turliuc@yahoo.com
    • Principal Investigator: Serban Turliuc, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; Placebo bid
Experimental: raloxifene	Drug: raloxifene; raloxifene 60 mg bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PANSS total score at the end of the trial.	PANSS will be assesed at weeks 5, 8 and end of study.	3 times

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Sheba Medical Center
• Investigators: Principal Investigator: Mark Weiser, MD, Sheba Medical Center

Publications and helpful links

General Publications

• Weiser M, Levi L, Burshtein S, Hagin M, Matei VP, Podea D, Miclutia I, Tiugan A, Pacala B, Grecu IG, Noy A, Zamora D, Davis JM. Raloxifene Plus Antipsychotics Versus Placebo Plus Antipsychotics in Severely Ill Decompensated Postmenopausal Women With Schizophrenia or Schizoaffective Disorder: A Randomized Controlled Trial. J Clin Psychiatry. 2017 Jul;78(7):e758-e765. doi: 10.4088/JCP.15m10498.

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Anticipated): December 1, 2012
• Study Completion (Anticipated): March 1, 2013

Study Registration Dates

• First Submitted: January 19, 2011
• First Submitted That Met QC Criteria: January 19, 2011
• First Posted (Estimate): January 20, 2011

Study Record Updates

• Last Update Posted (Estimate): January 20, 2011
• Last Update Submitted That Met QC Criteria: January 19, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: schizophrenia; schizoaffective disorder
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Disease; Psychotic Disorders; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Bone Density Conservation Agents; Estrogen Antagonists; Selective Estrogen Receptor Modulators; Estrogen Receptor Modulators; Raloxifene Hydrochloride
• Other Study ID Numbers: SHEBA-10-8287-MW-SHEBA