Clinical trial NCT01759485: Vitamin D for Schizophrenia
Official title: Vitamin D Supplementation as Adjunct to Clozapine-treated Chronic Schizophrenia Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Clozapine Resistant Schizophrenia
Keywords: Clozapine
Schizophrenia
Vitamin-D
Treatment-resistant
Lead sponsor: Geha Mental Health Center
Sponsor class: OTHER
First posted: 2013-01-03
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Males and females
2. Age 18-65 years
3. Diagnosis of schizophrenia according to DSM-IV-TR criteria, as confirmed by two senior psychiatrists
4. Total PANSS score \> 70
5. CGI-S \> 3
6. Clozapine treatment for at least 18 weeks
7. Vitamin D deficiency: plasma 25-OH-Vitamin D \<75 nmol/L (20-30 ng/mL)
8. Able to consume oral drops of vitamin-D
9. Able to sign informed consent

Exclusion Criteria:

1. Mental retardation
2. Organic brain disease
3. Known parathyroid disorder
4. Inborn/acquired vitamin D metabolism disorders
5. Patients already treated with vitamin D supplementation

Primary outcomes:
measure: Change in Positive and Negative Syndrome Scale total score
timeFrame: Baseline to 8 weeks
Secondary outcomes:
measure: Change in the MoCA Cognitive composite score
timeFrame: Baseline to 8 weeks
Other outcomes:
measure: Change in Positive and Negative Syndrome Scale sub-scores
timeFrame: Baseline to 8 weeks
Locations:
city: Petach-Tikva
country: Israel
facility: Geha Mental Health Center
Study officials:
References: