Raloxifene Augmentation in Patients With a Schizophrenia Spectrum Disorder

NCT03043820 | Completed Phase 3 DMC

• 3 other identifiers: NL.55343.041.162015-004483-1180-83600-98-40120
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study will test the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. 110 patients with a schizophrenia spectrum disorder will be recruited in a multicenter twelve-week, randomized, double-blind, placebo-controlled, parallel trial of adjunctive 120mg raloxifene treatment in addition to their usual antipsychotic medications. The investigators hypothesize that daily treatment with raloxifene 120 milligrams (mg) in addition to antipsychotic treatment improves cognition, reduces psychotic symptoms, increases social and personal functioning and reduces health care costs, as compared to placebo.

Conditions

Schizophrenia; Schizoaffective Disorder; Schizophreniform Disorder; Psychosis NOS

Keywords

raloxifene; selective estrogen receptor modulator (SERM); schizophrenia; psychosis; cognition; negative symptoms

Outcome Measures

Primary Outcomes (2)

• Change in symptom severity as measured with the Positive and Negative Symptom Scale (PANSS)

  Effect of the study therapies on symptom severity.

  Baseline, at 6 weeks of treatment, at 12 weeks of treatment (end of treatment) and 6 months after end of treatment (follow-up)

• Change in cognitive functioning as measured with the Brief Assessment of Cognition in Schizophrenia

  Effect of the study therapies on cognitive functioning

  Baseline, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)

Secondary Outcomes (8)

• Personal and social performance measured with the Personal and Social Performance scale (PSP)

  Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)

• Thought disorder severity as measured with the Thought And Language Disorder scale (TALD)

  Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)

• Participant's Quality of Life as measured with the EQ-5D-5L

  Baseline, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)

• Comorbid depression as measured with Beck's Depression Inventory (BDI).

  Baseline, at 6 weeks, at 12 weeks (end of treatment) and 6 months after end of treatment (follow-up)

• Use of health-recourses as measured with the iMTA-MCQ

  Baseline, at 12 weeks (end of treatment) and 6 months follow-up

Other Outcomes (2)

• Hormonal biomarkers for predicting treatment response to raloxifene

  Baseline and at 12 weeks of treatment

• Deoxyribonucleic acid analysis for predicting treatment response to raloxifene

  Baseline and at 12 weeks of treatment

Study Arms (2)

Raloxifene

ACTIVE COMPARATOR

Raloxifene 120 mg (2 tablets of 60mg) daily for 12 weeks.

Drug: Raloxifene

Placebo

PLACEBO COMPARATOR

Placebo 2 tablets daily for 12 weeks.

Drug: Placebo

Interventions

Raloxifene DRUG

Oral selective estrogen receptor modulator (SERM).

Also known as: Evista

Raloxifene

Placebo DRUG

Tablets identical in form and color to intervention.

Placebo

Eligibility Criteria

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

You may qualify if:

• A DSM-IV-R diagnosis of: 295.x (schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychotic disorder NOS)
• Capable of understanding the purpose and details of the study in order to provide written informed consent;
• On a stable dose of antipsychotic medication for at least two weeks;
• For female patients:
• Female patients who are sexually active must be willing and capable to use a non-estrogenic contraceptive (intrauterine device, cervical cap, condom or diaphragm) in case of sexual intercourse for the complete duration of the study;
• Female patients with post coital uterine bleeding must have documented normal PAP smear and pelvic examination in the preceding two years.

You may not qualify if:

• Pre-existing cardiovascular disease;
• History of thrombo-embolic events;
• History of breast cancer;
• Familial tendency to form blood clots (such as familial factor V Leiden);
• Use of vitamin K antagonists;
• Use of cholestyramine or other anion exchange resins;
• Hypertriglyceridemia (triglycerides \> 3 times the upper limit of normal (ULN));
• Liver function or enzyme disorders (serum bilirubin, alkaline phosphatase (AF), gamma-glutamyl transpeptidase (γ - GT), aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) \> 3 times the ULN as measured at baseline);
• Severe kidney failure (eGFR \<30 ml/min as measured at baseline);
• 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 in the past three months.
• For female patients:
• Abnormality observed during physical breast examination;
• Pregnancy or breast feeding;

Sponsors & Collaborators

• Iris Sommer: lead
• Julius Center: collaborator
• Rudolf Magnus Institute - University of Utrecht: collaborator
• GGZ Eindhoven: collaborator
• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): collaborator
• GGZ Centraal: collaborator
• Altrecht GGZ: collaborator
• Reinier van Arkel Group: collaborator
• Ziekenhuis Netwerk Antwerpen (ZNA): collaborator

Study Sites (1)

UMC Utrecht

Utrecht, 3508GA, Netherlands

Location

Related Publications (1)

• Heringa SM, Begemann MJ, Goverde AJ, Sommer IE. Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review. Schizophr Res. 2015 Nov;168(3):603-13. doi: 10.1016/j.schres.2015.04.002. Epub 2015 Apr 23.

  PMID: 25914107 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; Psychotic Disorders; Mental Disorders

Interventions

Raloxifene Hydrochloride

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

Study Officials

• Iris Sommer, Prof. dr.

  UMC Groningen

  PRINCIPAL INVESTIGATOR

• Bob Oranje, Ass. Prof.

  UMC Utrecht

  PRINCIPAL INVESTIGATOR

• Janna de Boer, MD

  UMC Utrecht

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Prof. dr. Iris Sommer

Study Record Dates

• First Submitted: October 25, 2016
• First Posted: February 6, 2017
• Study Start: August 1, 2016
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: October 8, 2021

Record last verified: 2021-10

Locations

NL (1)