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L-arginine in Treatment as Usual in Schizophrenia

Primary Purpose

Schizophrenia

Status

Completed

Phase

Not Applicable

Locations

Canada

Study Type

Interventional

Intervention

L-Arginine

About this trial

This is an interventional treatment trial for Schizophrenia

Eligibility Criteria

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

Inclusion Criteria:

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.

Exclusion Criteria:

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.
1. 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.
2. Patients receiving active treatments for Herpes virus as L-arginine may counteract the benefits of lysine to treat herpes virus
3. Patients who are currently receiving NSAIDs or other drugs that can cause significant stomach an gastrointestinal side-effects
4. Drugs that alter potassium levels in the body, such as ACE inhibitors and potassium sparing diuretics
5. Patients who are pregnant or plan to become pregnant while using this amino acid
6. Patients who are breastfeeding
7. Prior history of intolerance to L-arginine
8. Any significant change of psychotropic medications done within the previous 4 weeks
9. Diagnosis of substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-IV criteria

Sites / Locations

Alberta Hospital Edmonton

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

L-arginine first/placebo second

Placebo first/L-arginine second

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

Full Information

NCT ID

NCT00718510

First Posted

July 16, 2008

Last Updated

September 1, 2017

Sponsor

University of Alberta

Collaborators

Alberta Health services

1. Study Identification

Unique Protocol Identification Number

NCT00718510

Brief Title

L-arginine in Treatment as Usual in Schizophrenia

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

July 2011 (Actual)

Study Completion Date

October 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Alberta

Collaborators

Alberta Health services

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Schizophrenia

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

13 (Actual)

8. Arms, Groups, and Interventions

Arm Title

L-arginine first/placebo second

Arm Type

Active Comparator

Arm Description

Arm Title

Placebo first/L-arginine second

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

L-Arginine

Other Intervention Name(s)

Placebo

Intervention Description

3 grams, twice daily, oral administration

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Baseline and 3 Weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Mean Clinical Global Impression (CGI) Scale at 3 Weeks

Description

Time Frame

Baseline and 3 Weeks

Title

Change From Baseline in Mean Calgary Depression Scale for Schizophrenia (CDSS) at 3 Weeks

Description

Time Frame

Baseline and 3 Weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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 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

Overall Study Officials: