The primary objective of this trial is to investigate the proposed beneficial effect of raloxifene as compared to placebo when given for twelve weeks in addition to antipsychotic medication to patients with a psychotic disorder. We expect lower…
ID
Source
Brief title
Condition
- Schizophrenia and other psychotic disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary objective of this trial is to investigate the beneficial effect of
raloxifene as compared to placebo when given for twelve weeks in addition to
antipsychotic medication. We expect to find lower severity of psychotic and
cognitive symptoms as measured with the Positive And Negative Symptom Scale
(PANSS) and the Brief Assessment of Cognition in Schizophrenia (BACS) over the
course of 12 weeks.
Secondary outcome
Secondary outcomes are changes in negative symptoms (measured with BNSS),
changes in personal and social performance (measured with PSP), change in
severity of thought disorder (measured with TALD), quality of life (measured
with EQ-5D), use of healthcare and non-healthcare resources, comorbid
depression (measured with BDI), cognitive control (measured with a Stroop
Test), language production (measured by analyzing speech samples), DNA-profiles
and hormonal and inflammatory biomarkers.
Background summary
There is ample evidence that sex hormones may influence the course of
schizophrenia. Women with schizophrenia have a greater likelihood of developing
psychosis when estrogen levels are low, for instance around menopause. Several
trials have evaluated estrogen augmentation in women with schizophrenia,
however, long-term treatment is not safe as it has considerable side effects.
Selective Estrogen Receptor Modulators (SERMs), such as raloxifene, do not
carry these side effects. Three trials have described positive effects of
raloxifene augmentation in postmenopausal women with schizophrenia. To this
date, only one trial has studied the addition of raloxifene in premenopausal
women and in men, which show significant improvement on cognition but not on
psychotic symptoms. Their findings confirm the potential of raloxifene for
general use in patients with schizophrenia. At least one independent
replication is needed to guarantee implementation into clinical practice.
Furthermore, if a correlation between baseline hormonal levels and raloxifene
efficacy can be observed, this study can be used to start personalized
psychiatry.
Hypotheses: Daily treatment with raloxifene 120mg in addition to antipsychotic
treatment increases social and personal functioning, improves cognition,
reduces psychotic symptoms and health care costs, as compared to placebo.
Study objective
The primary objective of this trial is to investigate the proposed beneficial
effect of raloxifene as compared to placebo when given for twelve weeks in
addition to antipsychotic medication to patients with a psychotic disorder. We
expect lower severity of psychotic and cognitive symptoms as measured with the
Positive And Negative Symptom Scale (PANSS) and the Brief Assessment of
Cognition in Schizophrenia (BACS).
Secondary objectives concern change in negative symptoms as measured with the
Brief Negative Symptom Scale (BNSS) in functional outcome (PSP), change in
severity of thought disorder (TALD), change in health-related quality of life
and quality adjusted life years (QALY) outcomes using the EQ-5D, change in
cognitive control (Stroop Test), change in use of healthcare and non-healthcare
resources (using the institute for Medical Technology Assessment*s Medical
Consumption Questionnaire (iMTA-MCQ) and Productivity Cost Questionnaire
(iMTA-PCQ) respectively), change in comorbid depression will be monitored using
Beck*s Depression Inventory (BDI) and change in productive language will be
tested by analyzing speech recordings.
Study design
Randomized placebo-controlled multicenter double-blind trial
Intervention
Patients will be randomized 1:1 to either 120mg raloxifene or placebo daily,
in the form of identical tablets.
Study burden and risks
Use of raloxifene is associated with a small risk of side effects. The number
of patient visits will be limited to 4 visits and mainly requires time invested
for physical examinations, questionnaires and cognitive testing sessions
(around 9 hours in total over the course of 9 months). Blood will be drawn at
three occasions with negligible and known risks (e.g. irritation). The burden
and risks are acceptable while the benefits are expected to be considerable.
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
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;
- Use of antipsychotic medication and being on a stable dose of antipsychotic
medication for at least two weeks;
- Age over 18 years.,
For female patients:
- Female patients of childbearing potential (WOCBP; i.e. fertile, following
menarche and until becoming post-menopausal unless permanently sterile after
hysterectomy, bilateral salpingectomy and bilateral oophorectomy) 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 five years. If no documented
PAP smear is present, female patients with post coital uterine bleeding must be
willing to undergo a PAP smear .
- Female patients between the age of 52 and 75 must have a reported normal
mammogram as part of the Dutch *bevolkingsonderzoek* in the preceding two
years. In case a patient has not participated in the regular breast cancer
screening, female patients between de age of 52 and 75 must be willing to
undergo a mammogram.
Exclusion criteria
-Pre-existing cardiovascular disease (not including hypertension);
-History of thrombo-embolic events;
-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));
-History of breast cancer;
-Liver function or enzyme disorders (serum bilirubin, alkaline phosphatase
(AF), gamma-glutamyl transpeptidase (* - 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 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:
- Pregnancy or breast feeding
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004483-11-NL |
| CCMO | NL55343.041.16 |