L-arginine add-on Therapy in Patients With Schizophrenia

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Schizophrenia, Schizoaffective Disorder

Intervention / Treatment
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* Dietary Supplement: L-Arginine
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: L-Arginine-First<br>For the first three weeks, L-Arginine 3 g bid (500mg capsules 6 x 2), one week wash-out, then for the next three weeks placebo capsules (6 x 2) | Dietary Supplement: L-Arginine<br>* Experimental supplement<br>Other: Placebo<br>* Placebo capsules in the same color and shape with the experimental supplement<br>|
| Experimental: Placebo-First<br>For the first three weeks, placebo capsules (6 x 2), one week wash-out, then for the next three weeks L-Arginine 3 g bid (500 mg capsules 6 x 2) | Dietary Supplement: L-Arginine<br>* Experimental supplement<br>Other: Placebo<br>* Placebo capsules in the same color and shape with the experimental supplement<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| 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 | 
| Change from baseline in blood pressure |  | baseline and week 7 | 
| Change from baseline in heart rate |  | baseline and week 7 | 
| Change from baseline in temperature |  | baseline and week 7 | 
| Change from baseline in respiratory rate |  | baseline and week 7 | 
| Change from baseline in weight |  | baseline and week 7 | 
| Change from baseline in electrocardiogram |  | baseline and week 7 | 
| 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 | 
| Change from baseline in alanine aminotransferase |  | baseline and week 7 | 
| Change from baseline in aspartate aminotransferase |  | baseline and week 7 | 
| Change from baseline in alkaline phosphatase |  | baseline and week 7 | 
| Change from baseline in urea |  | baseline and week 7 | 
| Change from baseline in creatinine |  | baseline and week 7 | 
| Change from baseline in sodium |  | baseline and week 7 | 
| Change from baseline in potassium |  | baseline and week 7 | 
| Change from baseline in chloride |  | baseline and week 7 | 
| Change from baseline in calcium |  | baseline and week 7 | 
| Change from baseline in thyroid-stimulating hormone |  | baseline and week 7 | 
| Change from baseline in free T4 |  | baseline and week 7 | 
| Change from baseline in total cholesterol |  | baseline and week 7 | 
| Change from baseline in HDL |  | baseline and week 7 | 
| Change from baseline in LDL |  | baseline and week 7 | 
| Change from baseline in triglycerides |  | baseline and week 7 | 
| Change from baseline in human chorionic gonadotropin | Pregnancy test in women | baseline and week 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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schizophrenia, L-Arginine, nitric oxide, drug augmentation