Vitamin D for Schizophrenia

Study Overview
=================
Brief Summary
-----------------
Background: Despite improvements in medications, treatment delivery and rehabilitation, schizophrenia outcomes remain suboptimal. There are a proportion of 30-40% treatment-resistant schizophrenia patients. Multiple lines of evidence suggest that vitamin D is a neuro-active steroid that acts on brain development, leading to alterations in brain neurochemistry and adult brain function. Early deficiencies have been linked with neuropsychiatric disorders, such as schizophrenia, and adult deficiencies have been associated with adverse brain outcomes, including Parkinson's disease, Alzheimer's disease, depression and cognitive decline. Ecological studies support a potential role for vitamin D in schizophrenia. These data include studies that have explored the association between schizophrenia and winter/spring birth and also the apparent increased incidence and prevalence of schizophrenia at higher latitudes. Objective: To evaluate the effect of vitamin-D supplementation on the mental state of clozapine-treated chronic schizophrenia patients, and the relation of disease severity to serum vitamin D levels. Methods: the investigators will use a prospective, interventional, longitudinal, double blinded, placebo-controlled, randomized design. The investigators will recruit 50 clozapine-treated chronic schizophrenia patients, with low level of serum vitamin-D, that will be randomly assigned (1:1 ratio) to receive either weekly oral drops of vitamin D (Cholecalciferol) or oral drops of placebo for 8 weeks follow-up. Repeated assessments will include: clinical severity scales (PANSS, CGI), side effects (SAS, BARS, clozapine side effects), cognitive (MoCA), metabolic parameters and laboratory data. Patients who were assigned to placebo will be supplemented with vitamin D after the 8 weeks period, and then will be assessed again with the same protocol of vitamin D treated patients. All participants will be assessed again after 24 weeks after vitamin D initiation. Analysis: the investigators will use on-way ANOVA with repeated measures for comparison of vitamin D and control groups. The investigators will apply intention to treat and LOCF.

Official Title
-----------------
Vitamin D Supplementation as Adjunct to Clozapine-treated Chronic Schizophrenia Patients

Conditions
-----------------
Clozapine Resistant Schizophrenia

Intervention / Treatment
-----------------
* Drug: Vitamin D3
* Drug: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males and females Age 18-65 years Diagnosis of schizophrenia according to DSM-IV-TR criteria, as confirmed by two senior psychiatrists Total PANSS score > 70 CGI-S > 3 Clozapine treatment for at least 18 weeks Vitamin D deficiency: plasma 25-OH-Vitamin D <75 nmol/L (20-30 ng/mL) Able to consume oral drops of vitamin-D Able to sign informed consent Exclusion Criteria: Mental retardation Organic brain disease Known parathyroid disorder Inborn/acquired vitamin D metabolism disorders Patients already treated with vitamin D supplementation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D<br>Supplementation of Vitamin D as add-on to the regular anti-psychotic treatment | Drug: Vitamin D3<br>* once weekly oral drops preparation at a daily dose of 2000 IU X 7 = 14,000 IU per week (about 60 drops each week).<br>* Other names: Cholecalciferol;|
| Placebo Comparator: Placebo<br>Placebo as oral drops once weekly as add-on to the regular anti-psychotic treatment | Drug: placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Positive and Negative Syndrome Scale total score |  | Baseline to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the MoCA Cognitive composite score |  | Baseline to 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Clozapine, Schizophrenia, Vitamin-D, Treatment-resistant