L-arginine add-on Therapy in Patients With Schizophrenia

Schizophrenia Clinical Trial

Official title:

L-Arginine add-on Treatment for Schizophrenia: A Randomized, Double Blind, Placebo Controlled, Cross Over Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02398279
• Other study ID #: 011D01101013
• Status: Completed
• Phase: N/A
• First received: March 6, 2015
• Last updated: March 19, 2015
• Start date: June 2011
• Est. completion date: April 2013

Study information

• Verified date: March 2015
• Source: Hacettepe University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Turkey: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

This study evaluates the addition of L-Arginine to the usual regimen in the treatment of schizophrenia in adults. As a requisite of crossover design, half of the participants started with L-Arginine and the other half with placebo and switched over after a three weeks use and one week of a washout period.

Description:

L-arginine is the precursor of nitric oxide (NO), a neuromodulator of dopamine, gamma-aminobutyrate (GABA) and glutamate systems. Nitric oxide donors which increase NO levels at the cellular level could improve N-methyl-D-aspartate (NMDA) receptor dysfunction. Using L-arginine could bypass the blocked NMDA receptors and improve the therapeutic efficacy by reversing the dysfunction.

The investigators proposed that using L-Arginine, a dietary supplement in most cultures, might constitute a safe option as an add-on treatment which may display beneficial effects on positive, negative, cognitive and affective symptoms associated with schizophrenia.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: April 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Schizophrenia-Schizoaffective Disorder

• Clinical Global Impression >4

• Able to take oral medication and likely to comply the required evaluations

• On stable medication regimen for 8 weeks

• Competent and willing to give informed consent

Exclusion Criteria:

• Uncontrolled medical illness (renal disease, hepatic, cardiac diseases, gout, asthma, diabetes, sickle cell anemia, low-high blood pressure)

• History of Myocardial Infarction (MI)

• History of genital herpes infections/ receiving lysine containing treatments

• Pregnancy/ lactation

• Substance related and Addictive Disorders

• Drugs that might induce hypotension

• Intolerance to L-arginine and ingredients of placebo or L-arginine capsule

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Psychotic Disorders
• Schizoaffective Disorder
• Schizophrenia

Intervention

Dietary Supplement:
• L-Arginine
Experimental supplement

Other:
• Placebo
Placebo capsules in the same color and shape with the experimental supplement

Locations

Country	Name	City	State
Turkey	Hacettepe University Faculty of Medicine Department of Psychiatry	Ankara

Sponsors (1)

Lead Sponsor	Collaborator
Hacettepe University

Country where clinical trial is conducted

Turkey, 

References & Publications (3)

Böger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. Review. — View Citation

Maia-de-Oliveira JP, Trzesniak C, Oliveira IR, Kempton MJ, Rezende TM, Iego S, Baker GB, Dursun SM, Machado-de-Sousa JP, Hallak JE. Nitric oxide plasma/serum levels in patients with schizophrenia: a systematic review and meta-analysis. Rev Bras Psiquiatr. 2012 Oct;34 Suppl 2:S149-55. Review. English, Portuguese. — View Citation

Vayisoglu S, Anil Yagcioglu AE, Yagcioglu S, Karahan S, Karci O, Gürel SC, Yazici MK. Lamotrigine augmentation in patients with schizophrenia who show partial response to clozapine treatment. Schizophr Res. 2013 Jan;143(1):207-14. doi: 10.1016/j.schres.2012.11.006. Epub 2012 Dec 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in Positive and Negative Syndrome Scale	Evaluating change in Positive and Negative Syndrome Scale between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	No
Secondary	Change from baseline in Neuropsychological Test Battery	Evaluating change in Neuropsychological Test Battery between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	No
Secondary	Change from baseline in the The Calgary Depression Scale for Schizophrenia	Evaluating change in The Calgary Depression Scale for Schizophrenia between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	No
Secondary	Change from baseline in Clinical Global Impression - Severity	Evaluating change in Clinical Global Impression - Severity between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	No
Secondary	Change from baseline in Abnormal Involuntary Movement Scale	Evaluating change in Abnormal Involuntary Movement Scale between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	Yes
Secondary	Change from baseline in Uku Side Effects Rating Scale	Evaluating change in Uku Side Effects Rating Scale between baseline and Week 3, comparing subjects treated with L-Arginine for 3 weeks to subjects treated with placebo for 3 weeks.	baseline and week 3	Yes
Secondary	Change from baseline in blood pressure		baseline and week 7	Yes
Secondary	Change from baseline in heart rate		baseline and week 7	Yes
Secondary	Change from baseline in temperature		baseline and week 7	Yes
Secondary	Change from baseline in respiratory rate		baseline and week 7	Yes
Secondary	Change from baseline in weight		baseline and week 7	Yes
Secondary	Change from baseline in electrocardiogram		baseline and week 7	Yes
Secondary	Change from baseline in complete blood count	Composed of different measures. Change in any measure indicates impairment in the composite measure	baseline and week 7	Yes
Secondary	Change from baseline in alanine aminotransferase		baseline and week 7	Yes
Secondary	Change from baseline in aspartate aminotransferase		baseline and week 7	Yes
Secondary	Change from baseline in alkaline phosphatase		baseline and week 7	Yes
Secondary	Change from baseline in urea		baseline and week 7	Yes
Secondary	Change from baseline in creatinine		baseline and week 7	Yes
Secondary	Change from baseline in sodium		baseline and week 7	Yes
Secondary	Change from baseline in potassium		baseline and week 7	Yes
Secondary	Change from baseline in chloride		baseline and week 7	Yes
Secondary	Change from baseline in calcium		baseline and week 7	Yes
Secondary	Change from baseline in thyroid-stimulating hormone		baseline and week 7	Yes
Secondary	Change from baseline in free T4		baseline and week 7	Yes
Secondary	Change from baseline in total cholesterol		baseline and week 7	Yes
Secondary	Change from baseline in HDL		baseline and week 7	Yes
Secondary	Change from baseline in LDL		baseline and week 7	Yes
Secondary	Change from baseline in triglycerides		baseline and week 7	Yes
Secondary	Change from baseline in human chorionic gonadotropin	Pregnancy test in women	baseline and week 7	Yes