Raloxifene Augmentation in Patients With a Schizophrenia Spectrum Disorder

• Status: Completed
• Trial end date: 2021-07-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Iris Sommer
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Altrecht GGZ; GGZ Centraal; GGZ Eindhoven; Julius Center; Reinier van Arkel Group; Rudolf Magnus Institute - University of Utrecht; Rudolf Magnus Institute – University of Utrecht; Ziekenhuis Netwerk Antwerpen (ZNA)
• Treatments: Estrogen Receptor Modulators; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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;