Vitamin D for Schizophrenia

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

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.

Study Overview

• Status: Completed
• Conditions: Clozapine Resistant Schizophrenia
• Intervention / Treatment: Drug: placebo; Drug: Vitamin D3

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petach-Tikva, Israel, 45000
    • Geha Mental Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Outcome Measure	Time Frame
Change in Positive and Negative Syndrome Scale sub-scores	Baseline to 8 weeks

Collaborators and Investigators

• Sponsor: Geha Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2014
• Primary Completion (Actual): September 1, 2016
• Study Completion (Actual): February 28, 2017

Study Registration Dates

• First Submitted: December 4, 2012
• First Submitted That Met QC Criteria: December 29, 2012
• First Posted (Estimate): January 3, 2013

Study Record Updates

• Last Update Posted (Actual): April 13, 2017
• Last Update Submitted That Met QC Criteria: April 12, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: Schizophrenia; Clozapine; Treatment-resistant; Vitamin-D
• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: GMHC-VITD; 29-12 (Other Identifier: GMHC)