Targeted Vitamin D Treatment of Schizophrenia-Associated Hyperprolinemia

Launched by NYU LANGONE HEALTH · Jul 18, 2014

Keywords

ClinConnect Summary

25-hydroxyvitamin D (vitD) insufficiency is associated with cognitive decline and has long-been considered important in schizophrenia susceptibility. VitD supplementation has been suggested for those at-risk, and recent studies have demonstrated that vitD insufficiency extends into both adolescent and adult schizophrenia.

The mechanism by which vitD deficits confers risk is unknown. However, vitD is a transcriptional regulator, and the investigators recently found that vitD significantly up-regulates PRODH gene expression. This is important because the highest known genetic risk of schizop...

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • Inclusion Criteria for Recruitment
• • 1. Male and Female, all racial/ethnic groups, aged 18-65 years.
• • 2. Admission diagnosis of schizophrenia, schizophreniform disorder, or schizoaffective disorder.
• • 3. Capability to give informed consent.
• • Inclusion Criteria for Randomization and Trial Entry
• • 1. Fasting hyperprolinemia (defined as 2 standard deviations (SDs) above the gender-adjusted mean measured for historical controls: 203.3 micromolar (uM) for females and 327.6 uM for males).
• • 2. 25(OH)D insufficiency (\<30ng/ml).
• • 3. Confirmed diagnosis of schizophreniform disorder, schizophrenia or schizoaffective disorder.
• Exclusion Criteria:
• • Exclusion Criteria for Recruitment
• • 1. Organic brain disorders.
• • 2. Valproate treatment within 14 days, because of known proline up-regulatory effects.
• • 3. Pregnant women or women of child-bearing potential, who are not surgically-sterile or who are not using appropriate methods of birth control.
• • 4. Amino acid metabolism disorder diagnosis.
• • 5. Hypercalcemia (\>10.4mg/dL), hypercalciuria (\>0.20mg/mg), hyperthyroidism (\>65pg/ml) or history of renal stones, kidney disease, atherosclerosis, sarcoidosis, histoplasmosis and lymphoma.
• • 6. Chart record of HIV positive status.
• • 7. Treatment with clozapine, as this may reflect general treatment resistance.
• • Exclusion Criteria for Randomization and Trial Entry
• • 1. Abnormal serum/ urine metabolic lab values suggesting hypercalcemia (serum Calcium \>10.4mg/dL), hypercalciuria (urine calcium/urine creatinine \>0.20 mg/mg), or hyperthyroidism (parathyroid hormone (PTH) \> 65pg/ml).
• • 2. Initiation of Valproate treatment.
• • 3. Continued use of dietary supplementation, such as fish oil supplementation or vitamin D supplements (\>400 IU/day).