Selective Estrogen Receptor Modulators - A Potential Treatment for Psychotic Symptoms of Schizophrenia

NCT00361543 | Completed Phase 4

• 2 other identifiers: MAPrc 94/0603T-422
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the project is to investigate the use of Raloxifene (a new form of estrogen) in the treatment of women with schizophrenia and schizoaffective disorder. Raloxifene is a Selective Estrogen Receptor Modulator (SERM), which means that it can affect the central nervous system (CNS) effects of estrogen (eg. improving emotional symptoms, memory, information processing and concentration), without adversely affecting reproductive tissue/organs such as breast, uterus and ovaries. The investigators are conducting a double-blind, placebo controlled, three month study comparing the psychotic symptom response of women with schizophrenia in both groups. One group will receive standard antipsychotic medication plus 120mg Raloxifene, while the second group will receive standard antipsychotic medication plus oral placebo. Hypothesis 1: That the women receiving adjunctive Raloxifene would have a quicker recovery from psychotic symptoms, as measured on the rating scales, compared with the women receiving adjunctive placebo. Hypothesis 2: That the Raloxifene group would have better cognitive improvement than the placebo group.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder

Keywords

Schizophrenia; Mental Illness; SERM; Raloxifene; Cognition

Outcome Measures

Primary Outcomes (1)

• PANSS score at trial completion (12 weeks)

  baseline, week 2,4,6,8,10,12

Secondary Outcomes (4)

• MADRS score at trial completion (12 weeks)

  baseline, week 2,4,6,8,10,12

• Cognitive Test scores at trial completion (12weeks)

  baseline and week 12

• Adverse Symptom Checklist score at trial completion (12 weeks)

  baseline, week 2,4,6,8,10,12

• Hormone level change over study duration (12 weeks)

  baseline, weeks 4, 8, 12

Study Arms (2)

1

ACTIVE COMPARATOR

Raloxifene Hydrochloride

Drug: Raloxifene hydrochloride

2

PLACEBO COMPARATOR

placebo tablet

Other: Lactose Capsules

Interventions

Raloxifene hydrochloride DRUG

120 mg per capsule (1 tablet daily)

1

Lactose Capsules OTHER

1 tablet daily for 12 weeks

2

Eligibility Criteria

• Age: 45 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Physically well.
• A current DSM-IV diagnosis of schizophrenia or related disorder.
• years
• Able to give informed consent.
• PANSS total score \> 60 (1 - 7 scale) and a score of 4 (moderate) or more on two or more of the following PANSS items: delusions, hallucinatory behaviour, conceptual disorganization or suspiciousness.
• No abnormality observed during physical breast examination.
• Documented normal PAP smear and pelvic examination in the preceding two years.

You may not qualify if:

• Patients with known abnormalities in the hypothalamo-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, or undiagnosed vaginal bleeding.
• Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; presence of illness causing immobilisation.
• Patients whose psychotic illness is directly related to illicit substance use or who have a history of substance abuse or dependence during the last six months, or consumption of more than 30gm of alcohol (three standard drinks) per day.
• Smoking more than 20 cigarettes per day.
• Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet.

Sponsors & Collaborators

• The Alfred: lead
• Stanley Medical Research Institute: collaborator
• National Health and Medical Research Council, Australia: collaborator

Study Sites (1)

Monash Alfred Psychiatry Research Centre

Melbourne, Victoria, 3004, Australia

Location

Related Publications (2)

• Thomas N, Gurvich C, Hudaib AR, Gavrilidis E, Kulkarni J. Dissecting the syndrome of schizophrenia: Associations between symptomatology and hormone levels in women with schizophrenia. Psychiatry Res. 2019 Oct;280:112510. doi: 10.1016/j.psychres.2019.112510. Epub 2019 Aug 8.

  PMID: 31415936 DERIVED

• Kulkarni J, Gavrilidis E, Gwini SM, Worsley R, Grigg J, Warren A, Gurvich C, Gilbert H, Berk M, Davis SR. Effect of Adjunctive Raloxifene Therapy on Severity of Refractory Schizophrenia in Women: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Sep 1;73(9):947-54. doi: 10.1001/jamapsychiatry.2016.1383.

  PMID: 27438995 DERIVED

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Mental Disorders

Interventions

Raloxifene Hydrochloride; Lactose

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Tamoxifen; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Disaccharides; Oligosaccharides; Polysaccharides; Carbohydrates; Sugars

Study Officials

• Jayashri Kulkarni, MBBS, MPM, FRANZCP, PhD

  Bayside Health, Alfred Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 7, 2006
• First Posted: August 8, 2006
• Study Start: August 1, 2006
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 30, 2015

Record last verified: 2015-01

Locations

AU (1)