L-arginine in Treatment as Usual in Schizophrenia

NCT00718510 | Completed Results DMC

• 1 other identifier: CPAT7176
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline and 3 Weeks

Secondary Outcomes (2)

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

  Baseline and 3 Weeks

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

  Baseline and 3 Weeks

Study Arms (2)

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

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

Drug: L-Arginine

Interventions

L-Arginine DRUG

3 grams, twice daily, oral administration

Also known as: Placebo

L-arginine first/placebo second; Placebo first/L-arginine second

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alberta: lead
• Alberta Health services: collaborator

Study Sites (1)

Alberta Hospital Edmonton

Edmonton, Alberta, T5J 2J7, Canada

Location

MeSH Terms

Conditions

Schizophrenia

Interventions

Arginine

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Amino Acids, Essential

Results Point of Contact

• Title: Dr. Serdar Dursun
• Organization: Department of Psychiatry, University of Alberta

dursun@ualberta.ca

(780) 492-7319

Study Officials

• Serdar Dursun, M.D., Ph.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Glen Baker, Ph.D., D.Sc.

  University of Alberta

  PRINCIPAL INVESTIGATOR

• John C. Lind, Ph.D.

  Alberta Hospital Edmonton

  PRINCIPAL INVESTIGATOR

• Phil Tibbo, F.R.C.P.C.

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Mee-Sook Song, Ph.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

• Pierre Flor-Henry, F.R.C.P.C.

  Alberta Hospital Edmonton

  PRINCIPAL INVESTIGATOR

• Diane Cox, Ph.D.

  University of Alberta

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 18, 2008
• Study Start: September 1, 2009
• Primary Completion: July 1, 2011
• Study Completion: October 1, 2012
• Last Updated: September 5, 2017
• Results First Posted: September 5, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)