SchizophreniaNCT02398279
L-arginine add-on Therapy in Patients With Schizophrenia
A study testing L-Arginine in people with Schizophrenia and Schizoaffective Disorder, run by Hacettepe University at 1 site in Turkey (Türkiye).
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Schizophrenia, Schizoaffective Disorder
- What is being tested?
- L-Arginine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- Jun 2011to Apr 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Hacettepe University Faculty of Medicine Department of Psychiatry
Ankara, 06100
About this study
Official title: L-Arginine add-on Treatment for Schizophrenia: A Randomized, Double Blind, Placebo Controlled, Cross Over Study
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.
Read the 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.
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Being tested
- L-Arginine, Placebo
- Keywords
- schizophrenia, L-Arginine, nitric oxide, drug augmentation
- Medical subject headings
- Schizophrenia, Psychotic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-ArginineDietary supplement
Experimental supplement
PlaceboOther
Placebo capsules in the same color and shape with the experimental supplement
| Study group | Role | What they receive |
|---|---|---|
| L-Arginine-First | Experimental | 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) Receives: Dietary Supplement: L-Arginine; Other: Placebo |
| Placebo-First | Experimental | 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) Receives: Dietary Supplement: L-Arginine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline and week 3
Secondary outcomes (28)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: baseline and week 3
Change from baseline in blood pressure
Measured: baseline and week 7
Change from baseline in heart rate
Measured: baseline and week 7
Change from baseline in temperature
Measured: baseline and week 7
Change from baseline in respiratory rate
Measured: baseline and week 7
Change from baseline in weight
Measured: baseline and week 7
Change from baseline in electrocardiogram
Measured: 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
Measured: baseline and week 7
Change from baseline in alanine aminotransferase
Measured: baseline and week 7
Change from baseline in aspartate aminotransferase
Measured: baseline and week 7
Change from baseline in alkaline phosphatase
Measured: baseline and week 7
Change from baseline in urea
Measured: baseline and week 7
Change from baseline in creatinine
Measured: baseline and week 7
Change from baseline in sodium
Measured: baseline and week 7
Change from baseline in potassium
Measured: baseline and week 7
Change from baseline in chloride
Measured: baseline and week 7
Change from baseline in calcium
Measured: baseline and week 7
Change from baseline in thyroid-stimulating hormone
Measured: baseline and week 7
Change from baseline in free T4
Measured: baseline and week 7
Change from baseline in total cholesterol
Measured: baseline and week 7
Change from baseline in HDL
Measured: baseline and week 7
Change from baseline in LDL
Measured: baseline and week 7
Change from baseline in triglycerides
Measured: baseline and week 7
Change from baseline in human chorionic gonadotropin
Pregnancy test in women
Measured: baseline and week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2015 (estimated)
- Study startJun 2011
- Primary completionDec 2012
- Study completionApr 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by Hacettepe UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hacettepe University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, M. Kazim Yazici, Hacettepe University
- Investigators
- Kazım M Yazıcı, MD, Principal investigator, Hacettepe University Faculty of Medicine Department of Psychiatry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02398279
- Sponsor's protocol ID
- 011D01101013
- Status last verified
- Mar 2015
- First submitted
- 6 Mar 2015
- Last updated
- 25 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Boger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. doi: 10.1093/jn/137.6.1650S.
PubMed 17513442Maia-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.
PubMed 23429845Vayisoglu 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.
PubMed 23217729Kocyigit 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.
PubMed 30260460
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- L-Arginine add-on Treatment for Schizophrenia: A Randomized, Double Blind, Placebo Controlled, Cross Over Study
- ClinicalTrials.gov ID
- NCT02398279
- Acronym / sponsor ID
- 011D01101013
- Conditions
- Schizophrenia, Schizoaffective Disorder
- Keywords
- schizophrenia, L-Arginine, nitric oxide, drug augmentation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Hacettepe UniversityUniversity, hospital or other
- Study start
- Jun 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 25 Mar 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| L-Arginine-First | Experimental | Dietary Supplement: L-Arginine, Other: PlaceboFor 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) |
| Placebo-First | Experimental | Dietary Supplement: L-Arginine, Other: PlaceboFor 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) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| L-ArginineExperimental supplement | Dietary supplement | L-Arginine-First, Placebo-First |
| PlaceboPlacebo capsules in the same color and shape with the experimental supplement | Other | L-Arginine-First, Placebo-First |
Primary outcome
Change from baseline in Positive and Negative Syndrome Scale
Time frame: baseline and week 3
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.
28 secondary outcomes
Change from baseline in Neuropsychological Test Battery
Time frame: baseline and week 3
Change from baseline in the The Calgary Depression Scale for Schizophrenia
Time frame: baseline and week 3
Change from baseline in Clinical Global Impression - Severity
Time frame: baseline and week 3
Change from baseline in Abnormal Involuntary Movement Scale
Time frame: baseline and week 3
Change from baseline in Uku Side Effects Rating Scale
Time frame: baseline and week 3
Change from baseline in blood pressure
Time frame: baseline and week 7
Change from baseline in heart rate
Time frame: baseline and week 7
Change from baseline in temperature
Time frame: baseline and week 7
Change from baseline in respiratory rate
Time frame: baseline and week 7
Change from baseline in weight
Time frame: baseline and week 7
Change from baseline in electrocardiogram
Time frame: baseline and week 7
Change from baseline in complete blood count
Time frame: baseline and week 7
Change from baseline in alanine aminotransferase
Time frame: baseline and week 7
Change from baseline in aspartate aminotransferase
Time frame: baseline and week 7
Change from baseline in alkaline phosphatase
Time frame: baseline and week 7
Change from baseline in urea
Time frame: baseline and week 7
Change from baseline in creatinine
Time frame: baseline and week 7
Change from baseline in sodium
Time frame: baseline and week 7
Change from baseline in potassium
Time frame: baseline and week 7
Change from baseline in chloride
Time frame: baseline and week 7
Change from baseline in calcium
Time frame: baseline and week 7
Change from baseline in thyroid-stimulating hormone
Time frame: baseline and week 7
Change from baseline in free T4
Time frame: baseline and week 7
Change from baseline in total cholesterol
Time frame: baseline and week 7
Change from baseline in HDL
Time frame: baseline and week 7
Change from baseline in LDL
Time frame: baseline and week 7
Change from baseline in triglycerides
Time frame: baseline and week 7
Change from baseline in human chorionic gonadotropin
Time frame: baseline and week 7
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2015.
- Background: PubMed 17513442Boger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. doi: 10.1093/jn/137.6.1650S.
- Background: PubMed 23429845Maia-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.
- Background: PubMed 23217729Vayisoglu 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.
- Derived from this study: PubMed 30260460Kocyigit 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kazım M Yazıcı, MD principal investigator
Hacettepe University Faculty of Medicine Department of Psychiatry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-Arginine in people with Schizophrenia and Schizoaffective Disorder, run by Hacettepe University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in Positive and Negative Syndrome Scale (time frame: baseline and week 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02398279, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Mar 2015; AzTrials last refreshed its copy on 7 Nov 2026.