Clinical trial NCT02398279: L-arginine add-on Therapy in Patients With Schizophrenia
Official title: L-Arginine add-on Treatment for Schizophrenia: A Randomized, Double Blind, Placebo Controlled, Cross Over Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Schizoaffective Disorder
Keywords: schizophrenia
L-Arginine
nitric oxide
drug augmentation
Lead sponsor: Hacettepe University
Sponsor class: OTHER
First posted: 2015-03-25
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change from baseline in Positive and Negative Syndrome Scale
timeFrame: baseline and week 3
Secondary outcomes:
measure: Change from baseline in Neuropsychological Test Battery
timeFrame: baseline and week 3
measure: Change from baseline in the The Calgary Depression Scale for Schizophrenia
timeFrame: baseline and week 3
measure: Change from baseline in Clinical Global Impression - Severity
timeFrame: baseline and week 3
measure: Change from baseline in Abnormal Involuntary Movement Scale
timeFrame: baseline and week 3
measure: Change from baseline in Uku Side Effects Rating Scale
timeFrame: baseline and week 3
measure: Change from baseline in blood pressure
timeFrame: baseline and week 7
measure: Change from baseline in heart rate
timeFrame: baseline and week 7
measure: Change from baseline in temperature
timeFrame: baseline and week 7
measure: Change from baseline in respiratory rate
timeFrame: baseline and week 7
measure: Change from baseline in weight
timeFrame: baseline and week 7
measure: Change from baseline in electrocardiogram
timeFrame: baseline and week 7
measure: Change from baseline in complete blood count
timeFrame: baseline and week 7
measure: Change from baseline in alanine aminotransferase
timeFrame: baseline and week 7
measure: Change from baseline in aspartate aminotransferase
timeFrame: baseline and week 7
measure: Change from baseline in alkaline phosphatase
timeFrame: baseline and week 7
measure: Change from baseline in urea
timeFrame: baseline and week 7
measure: Change from baseline in creatinine
timeFrame: baseline and week 7
measure: Change from baseline in sodium
timeFrame: baseline and week 7
measure: Change from baseline in potassium
timeFrame: baseline and week 7
measure: Change from baseline in chloride
timeFrame: baseline and week 7
measure: Change from baseline in calcium
timeFrame: baseline and week 7
measure: Change from baseline in thyroid-stimulating hormone
timeFrame: baseline and week 7
measure: Change from baseline in free T4
timeFrame: baseline and week 7
measure: Change from baseline in total cholesterol
timeFrame: baseline and week 7
measure: Change from baseline in HDL
timeFrame: baseline and week 7
measure: Change from baseline in LDL
timeFrame: baseline and week 7
measure: Change from baseline in triglycerides
timeFrame: baseline and week 7
measure: Change from baseline in human chorionic gonadotropin
timeFrame: baseline and week 7
Other outcomes:
Locations:
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine Department of Psychiatry
Study officials:
affiliation: Hacettepe University Faculty of Medicine Department of Psychiatry
name: Kazım M Yazıcı, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Boger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. doi: 10.1093/jn/137.6.1650S.
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. Braz J Psychiatry. 2012 Oct;34 Suppl 2:S149-55. doi: 10.1016/j.rbp.2012.07.001. English, Portuguese.
citation: Vayisoglu S, Anil Yagcioglu AE, Yagcioglu S, Karahan S, Karci O, Gurel 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.
citation: Kocyigit Y, Yoca G, Karahan S, Ayhan Y, Yazici MK. [L-Arginine Add-On Treatment for Schizophrenia: A Randomized,Double-Blind, Placebo-Controlled, Crossover Study]. Turk Psikiyatri Derg. 2018 Fall;29(3):147-153. Turkish.