L-arginine in Treatment as Usual in Schizophrenia

A study testing L-Arginine in people with Schizophrenia, run by University of Alberta at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

STUDY OBJECTIVES: To determine whether the addition of L-arginine to treatment as usual (TAU) in schizophrenia further improves and enhances therapeutic efficacy (positive, negative and depressive symptoms) and effectiveness of antipsychotic treatment STUDY POPULATION: Patients diagnosed (DSM-IV criteria) with… Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Schizophrenia
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: 13 participants
Where: 1 siteCanada
Study dates: Sep 2009to Oct 2012
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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

Aged 18-65 years
Diagnoses of schizophrenia or schizoaffective disorder using the Diagnostic and Statistical Manual-IV (DSM-IV) criteria
Competent and willing to give informed consent
Able to take oral medication and likely to complete the required evaluations.
Medication remained stable 4 weeks prior to baseline.
Female participants of child bearing capability must be willing to use adequate contraceptives (4.6.1a) for the duration of the study, and, willing to have a pregnancy test pretreatment and during the study.
Adequate contraception is defined as use of contraceptive double barrier system (i.e. condom and spermicide) or contraceptive implant, oral contraceptive or injected depot contraceptive plus other form of contraceptive, i.e. condom. Females will be considered incapable of child bearing if they are one year postmenopausal or irreversibly surgically sterilised.

Who cannot join

Relevant medical illness [serious renal, diabetes, hepatic, cardiac, low- or high-blood-pressure or other illnesses] in the opinion of the investigators. In particular, history of past or recent cardiac illness, MI and abnormal ECG and current treatments for cardiac illness. The results of the Laboratory Investigations (LFT, TFT, RFT, WBC, ECG, platelets, blood chemistry, lipids, weight/BMI) will be taken into account in determining the exclusion criteria.
Relevant medical illness will be determined in the first instance by asking the patients mental health care team if the patient has any medical condition/problems. After consent has been obtained, the research nurse/research doctor will then have access to the patient's notes and if necessary communicate with his/her GP and will assess patient eligibility to take part in the clinical trial by scrutinising the patient's past medical history, most recent blood results, electrocardiograms, as well as any physical tests that have been performed on the patient. If there are any deviations from the 'norm' the investigators will assess the eligibility of the individual patient.
Patients receiving active treatments for Herpes virus as L-arginine may counteract the benefits of lysine to treat herpes virus
Patients who are currently receiving NSAIDs or other drugs that can cause significant stomach an gastrointestinal side-effects
Drugs that alter potassium levels in the body, such as ACE inhibitors and potassium sparing diuretics
Patients who are pregnant or plan to become pregnant while using this amino acid

Show all 10Show fewer

Patients who are breastfeeding
Prior history of intolerance to L-arginine
Any significant change of psychotropic medications done within the previous 4 weeks
Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria

Trial locations and contacts

1 site in 1 country.

Canada1 site

Alberta Hospital Edmonton
Edmonton, Alberta, T5J 2J7

Other trials in Canada

About this study

Official title: A Randomised, Double-blind, Cross-over, Placebo Controlled, Adjunctive-treatment of L-arginine Added to Treatment-as-usual (TAU) in Schizophrenia

STUDY POPULATION: Patients diagnosed (DSM-IV criteria) with schizophrenia or schizoaffective disorder

Total expected number of patients: 14

INVESTIGATIONAL COMPOUND: L-arginine capsules, 3 grams of L-arginine given twice a day (total daily dose of 6 grams/day)

DURATION OF ACTIVE TREATMENT: 3 weeks followed by wash-out phase of 5 days and 3 weeks of second treatment phase (cross-over design)

EVALUATION CRITERIA: Primary (efficacy) outcomes: PANSS scores. Secondary outcomes: Calgary Depression Scale for schizophrenia, CGI; AIMS, UKU-assessment of side-effects

ASSESSMENT SCHEDULE: Treatment arm 1: Baseline, weeks: 1,2,3, wash-out phase; week 4, cross-over phase: treatment phase-2; weeks 5,6,7

STATISTICAL CONSIDERATIONS: Analysis of variance of outcome measures with treatment as the between-subject factor and pre- and post-treatment scores as within- subjects factors.

DURATION OF STUDY PERIOD: Patient recruitment to be completed in 12 months, study full completion 18 months.

Read the detailed description

In the current study, our goals were to examine the clinical benefits of the nitric oxide (NO) donor and main precursor of NO, L-arginine, to further improve the symptoms of schizophrenia with minimum or no additional side-effects. L-Arginine is classified as a semi-essential or conditionally essential amino acid depending on the developmental stage and health status of the individual. Glutamate N-methyl-D-aspartate (NMDA) receptors have functional connections to the NO system in the brain. Dysfunction of connectivity of the neuroregulators glutamate and NO have been implicated in mechanisms of psychosis. Therefore, any downstream effects of NMDA dysfunction in schizophrenia may be ultimately mediated by the NO system at a cellular level. As an augmenting treatment to antipsychotic therapy, we examined the ability of L-arginine to further improve residual symptoms in the illness.

Conditions: Schizophrenia
Being tested: L-Arginine
Medical subject headings: Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

L-ArginineDrug
Also called Placebo
3 grams, twice daily, oral administration

Study groups in NCT00718510
Study group	Role	What they receive
L-arginine first/placebo second	Active comparator	Patients with diagnosis of schizophrenia will be randomised to receive L-arginine first/placebo second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization Receives: Drug: L-Arginine
Placebo first/L-arginine second	Placebo comparator	Patients with diagnosis of schizophrenia will be randomised to receive placebo first/L-arginine second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization Receives: Drug: L-Arginine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change From Baseline in Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks
The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score and PANSS positive, negative and general psychopathology subscale scores. The PANSS is a 30-item scale used to evaluate the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranges from 30 to 210 with a higher score indicating a greater severity of symptoms. The PANSS positive symptom subscale score (7 items) ranges from 7=absent to 49=extreme; the PANSS negative subscale score (7 items) ranges from 7=absent to 49=extreme; and the PANSS general psychopathology subscare score (16 items) ranges from 16=absent to 112=extreme.
Measured: Baseline and 3 Weeks

Secondary outcomes (2)

Change From Baseline in Mean Clinical Global Impression (CGI) Scale at 3 Weeks
The Secondary Outcome Measure was the Clinical Global Impression (CGI) scale. The CGI is a 3-item scale that rates treatment response and monitors the clinical course of all psychiatric illnesses including schizophrenia. Within the CGI, the Severity of Illness was rated on a 7-point scale, 0=not assessed to 7=among the most severely ill patients. For Global Improvement, the total improvement following treatment as compared to at baseline of the trial was rated on a 7-point scale, 0=not assessed to 7=very much worse.
Measured: Baseline and 3 Weeks
Change From Baseline in Mean Calgary Depression Scale for Schizophrenia (CDSS) at 3 Weeks
The Secondary Outcome Measure was the Calgary Depression Scale for Schizophenia (CDSS). The CDSS is a 9-item scale that is used to rate the depressive symptoms in patients with schizophrenia. For each CDSS item, symptom severity was rated on a 3-point scale, from 0=absent to 3=severe. The CDSS total score ranges from 0 to 27 with a higher score indicating a greater severity of symptoms.
Measured: Baseline and 3 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2009Oct 2012

First posted18 Jul 2008 (estimated)
Study startSep 2009
Primary completionJul 2011
Study completionOct 2012

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for SchizophreniaStudies of the same condition, open and under way.
More trials run by University of AlbertaThe 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: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00718510
Sponsor's protocol ID: CPAT7176
Status last verified: Sep 2017
First submitted: 16 Jul 2008
Last updated: 5 Sep 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomised, Double-blind, Cross-over, Placebo Controlled, Adjunctive-treatment of L-arginine Added to Treatment-as-usual (TAU) in Schizophrenia
ClinicalTrials.gov ID: NCT00718510
Acronym / sponsor ID: CPAT7176
Conditions: Schizophrenia
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: University of AlbertaUniversity, hospital or other
Collaborators: Alberta Health services
Study start: Sep 2009
Primary completion: Jul 2011 (actual)
Study completion: Oct 2012 (actual)
First posted: 18 Jul 2008 (estimated)
Results: Posted 5 Sep 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

STUDY POPULATION: Patients diagnosed (DSM-IV criteria) with schizophrenia or schizoaffective disorder

Total expected number of patients: 14

INVESTIGATIONAL COMPOUND: L-arginine capsules, 3 grams of L-arginine given twice a day (total daily dose of 6 grams/day)

DURATION OF ACTIVE TREATMENT: 3 weeks followed by wash-out phase of 5 days and 3 weeks of second treatment phase (cross-over design)

EVALUATION CRITERIA: Primary (efficacy) outcomes: PANSS scores. Secondary outcomes: Calgary Depression Scale for schizophrenia, CGI; AIMS, UKU-assessment of side-effects

ASSESSMENT SCHEDULE: Treatment arm 1: Baseline, weeks: 1,2,3, wash-out phase; week 4, cross-over phase: treatment phase-2; weeks 5,6,7

STATISTICAL CONSIDERATIONS: Analysis of variance of outcome measures with treatment as the between-subject factor and pre- and post-treatment scores as within- subjects factors.

DURATION OF STUDY PERIOD: Patient recruitment to be completed in 12 months, study full completion 18 months.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
L-arginine first/placebo second	Active comparator	Drug: L-ArgininePatients with diagnosis of schizophrenia will be randomised to receive L-arginine first/placebo second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization
Placebo first/L-arginine second	Placebo comparator	Drug: L-ArgininePatients with diagnosis of schizophrenia will be randomised to receive placebo first/L-arginine second 3 grams bid (cross-over design) in addition to treatment as usual. The active treatment period will be 3 weeks, with a wash-out period of 5 days and re-commencing on the alternative arm of the randomization

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Aged 18-65 years
Diagnoses of schizophrenia or schizoaffective disorder using the Diagnostic and Statistical Manual-IV (DSM-IV) criteria
Competent and willing to give informed consent
Able to take oral medication and likely to complete the required evaluations.
Medication remained stable 4 weeks prior to baseline.

Key exclusion criteria (10 listed)

Relevant medical illness [serious renal, diabetes, hepatic, cardiac, low- or high-blood-pressure or other illnesses] in the opinion of the investigators. In particular, history of past or recent cardiac illness, MI and abnormal ECG and current treatments for cardiac illness. The results of the Laboratory Investigations (LFT, TFT, RFT, WBC, ECG, platelets, blood chemistry, lipids, weight/BMI) will be taken into account in determining the exclusion criteria.

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-ArginineAlso: Placebo3 grams, twice daily, oral administration	Drug	L-arginine first/placebo second, Placebo first/L-arginine second

Primary outcome

Change From Baseline in Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks
Time frame: Baseline and 3 Weeks
The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score and PANSS positive, negative and general psychopathology subscale scores. The PANSS is a 30-item scale used to evaluate the symptoms of schizophrenia. For each PANSS item, symptom severity was rated on a 7-point scale, from 1=absent to 7=extreme. The PANSS total score (30 items) ranges from 30 to 210 with a higher score indicating a greater severity of symptoms. The PANSS positive symptom subscale score (7 items) ranges from 7=absent to 49=extreme; the PANSS negative subscale score (7 items) ranges from 7=absent to 49=extreme; and the PANSS general psychopathology subscare score (16 items) ranges from 16=absent to 112=extreme.

2 secondary outcomes

Change From Baseline in Mean Clinical Global Impression (CGI) Scale at 3 Weeks
Time frame: Baseline and 3 Weeks
Change From Baseline in Mean Calgary Depression Scale for Schizophrenia (CDSS) at 3 Weeks
Time frame: Baseline and 3 Weeks

Results and safety

Results posted to the registry on 5 Sep 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
L-arginine Treatment First, Placebo Treatment Second	7	7
Placebo Treatment First, L-arginine Treatment Second	8	7

Primary outcome: Change From Baseline in Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks

Time frame: Baseline and 3 Weeks. Mean (Standard Deviation). Unit: units on a scale

Measure	L-arginine n = 13	Placebo n = 13
PANSS Total Score at Baseline	71.6 (7.2)	72.2 (5.7)
PANSS Total Score at 3 Weeks	68.0 (7.2)	70.2 (7.0)
PANSS Positive Scale at Baseline	14.6 (4.4)	14.3 (4.5)
PANSS Positive Scale at 3 Weeks	14.5 (4.6)	13.6 (4.0)
PANSS Negative Scale at Baseline	22.8 (5.0)	22.6 (4.3)
PANSS Negative Scale at 3 Weeks	21.9 (5.2)	22.2 (5.2)
PANSS General Psychopathology Score at Baseline	33.4 (4.4)	34.4 (2.7)
PANSS General Psychopathology Score at 3 Weeks	31.2 (3.9)	33.6 (3.7)

L-arginine vs Placebo: p <0.05, ANOVA

Population analysed: All participants who received all doses of each intervention and completed all study visits were included in the efficacy analysis

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Three weeks for each intervention. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
L-arginine	0 of 13 (0%)	0 of 13 (0%)	0 of 13
Placebo	0 of 13 (0%)	0 of 13 (0%)	0 of 13

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Sep 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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.

Serdar Dursun, M.D., Ph.D. principal investigator

University of Alberta

Glen Baker, Ph.D., D.Sc. principal investigator

University of Alberta

John C. Lind, Ph.D. principal investigator

Alberta Hospital Edmonton

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, run by University of Alberta at 1 site in Canada.

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 7 inclusion and 10 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 5 Sep 2017. 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 Canada. 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 5 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 Mean Positive and Negative Syndrome Scale (PANSS) Total and Positive, Negative and General Psychopathology Subscale Scores at 3 Weeks (time frame: Baseline and 3 Weeks). 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 NCT00718510.

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 5 Sep 2017.