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L-arginine add-on Therapy in Patients With Schizophrenia

Primary Purpose

Schizophrenia, Schizoaffective Disorder

Status
Completed
Phase
Not Applicable
Locations
Turkey
Study Type
Interventional
Intervention
L-Arginine
Placebo
Sponsored by
Hacettepe University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Schizophrenia focused on measuring schizophrenia, L-Arginine, nitric oxide, drug augmentation

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Hacettepe University Faculty of Medicine Department of Psychiatry

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

L-Arginine-First

Placebo-First

Arm Description

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)

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
Change from baseline in blood pressure
Change from baseline in heart rate
Change from baseline in temperature
Change from baseline in respiratory rate
Change from baseline in weight
Change from baseline in electrocardiogram
Change from baseline in complete blood count
Composed of different measures. Change in any measure indicates impairment in the composite measure
Change from baseline in alanine aminotransferase
Change from baseline in aspartate aminotransferase
Change from baseline in alkaline phosphatase
Change from baseline in urea
Change from baseline in creatinine
Change from baseline in sodium
Change from baseline in potassium
Change from baseline in chloride
Change from baseline in calcium
Change from baseline in thyroid-stimulating hormone
Change from baseline in free T4
Change from baseline in total cholesterol
Change from baseline in HDL
Change from baseline in LDL
Change from baseline in triglycerides
Change from baseline in human chorionic gonadotropin
Pregnancy test in women

Full Information

First Posted
March 6, 2015
Last Updated
March 19, 2015
Sponsor
Hacettepe University
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1. Study Identification

Unique Protocol Identification Number
NCT02398279
Brief Title
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

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Completed
Study Start Date
June 2011 (undefined)
Primary Completion Date
December 2012 (Actual)
Study Completion Date
April 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Hacettepe University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorder
Keywords
schizophrenia, L-Arginine, nitric oxide, drug augmentation

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Allocation
Randomized
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
L-Arginine-First
Arm Type
Experimental
Arm Description
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)
Arm Title
Placebo-First
Arm Type
Experimental
Arm Description
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)
Intervention Type
Dietary Supplement
Intervention Name(s)
L-Arginine
Intervention Description
Experimental supplement
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo capsules in the same color and shape with the experimental supplement
Primary Outcome Measure Information:
Title
Change from baseline in Positive and Negative Syndrome Scale
Description
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.
Time Frame
baseline and week 3
Secondary Outcome Measure Information:
Title
Change from baseline in Neuropsychological Test Battery
Description
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.
Time Frame
baseline and week 3
Title
Change from baseline in the The Calgary Depression Scale for Schizophrenia
Description
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.
Time Frame
baseline and week 3
Title
Change from baseline in Clinical Global Impression - Severity
Description
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.
Time Frame
baseline and week 3
Title
Change from baseline in Abnormal Involuntary Movement Scale
Description
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.
Time Frame
baseline and week 3
Title
Change from baseline in Uku Side Effects Rating Scale
Description
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.
Time Frame
baseline and week 3
Title
Change from baseline in blood pressure
Time Frame
baseline and week 7
Title
Change from baseline in heart rate
Time Frame
baseline and week 7
Title
Change from baseline in temperature
Time Frame
baseline and week 7
Title
Change from baseline in respiratory rate
Time Frame
baseline and week 7
Title
Change from baseline in weight
Time Frame
baseline and week 7
Title
Change from baseline in electrocardiogram
Time Frame
baseline and week 7
Title
Change from baseline in complete blood count
Description
Composed of different measures. Change in any measure indicates impairment in the composite measure
Time Frame
baseline and week 7
Title
Change from baseline in alanine aminotransferase
Time Frame
baseline and week 7
Title
Change from baseline in aspartate aminotransferase
Time Frame
baseline and week 7
Title
Change from baseline in alkaline phosphatase
Time Frame
baseline and week 7
Title
Change from baseline in urea
Time Frame
baseline and week 7
Title
Change from baseline in creatinine
Time Frame
baseline and week 7
Title
Change from baseline in sodium
Time Frame
baseline and week 7
Title
Change from baseline in potassium
Time Frame
baseline and week 7
Title
Change from baseline in chloride
Time Frame
baseline and week 7
Title
Change from baseline in calcium
Time Frame
baseline and week 7
Title
Change from baseline in thyroid-stimulating hormone
Time Frame
baseline and week 7
Title
Change from baseline in free T4
Time Frame
baseline and week 7
Title
Change from baseline in total cholesterol
Time Frame
baseline and week 7
Title
Change from baseline in HDL
Time Frame
baseline and week 7
Title
Change from baseline in LDL
Time Frame
baseline and week 7
Title
Change from baseline in triglycerides
Time Frame
baseline and week 7
Title
Change from baseline in human chorionic gonadotropin
Description
Pregnancy test in women
Time Frame
baseline and week 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kazım M Yazıcı, MD
Organizational Affiliation
Hacettepe University Faculty of Medicine Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hacettepe University Faculty of Medicine Department of Psychiatry
City
Ankara
ZIP/Postal Code
06100
Country
Turkey

12. IPD Sharing Statement

Citations:
PubMed Identifier
17513442
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.
Results Reference
background
PubMed Identifier
23429845
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.
Results Reference
background
PubMed Identifier
23217729
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.
Results Reference
background
PubMed Identifier
30260460
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.
Results Reference
derived

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L-arginine add-on Therapy in Patients With Schizophrenia

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