Clinical trial NCT03510741: Sodium Benzoate and/or N-Acetylcysteine Added to TAU in Patients With Early Schizophrenia Spectrum Disorder.
Official title: A Multicentre 12-week Randomised Double-blind Placebo Controlled Feasibility Trial of Sodium Benzoate and/or N-acetylcysteine Added to TAU in Patients With Early Schizophrenia Spectrum Disorder.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Schizophrenia
Schizophreniform Disorders
Schizoaffective Disorder
Keywords: Schizophrenia
Sodium Benzoate
N-Acetylcysteine
NMDA receptor
Psychopharmacology
Anti-oxidant
Inflammation
Lead sponsor: Pakistan Institute of Living and Learning
Sponsor class: OTHER
First posted: 2018-04-27
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: This will be a 2x2 factorial design trial
Primary purpose: OTHER

Brief summary: This study aims to determine if the addition of Sodium Benzoate and / or NAC to TAU will be acceptable and tolerable and result in overall improvement of symptoms, social and cognitive functioning in patients with early schizophrenia spectrum disorder.


Eligibility criteria: Inclusion Criteria:

1. Male/Female patients aged between 18-35 years.
2. Diagnosis of schizophrenia confirmed by SCID interview meeting DSM-V criteria for schizophrenia, schizophreniform or schizoaffective psychosis.
3. Stable on medication for the past four weeks
4. In contact with mental health services
5. Within 5 years of diagnosis of psychotic illness
6. Able to demonstrate the capacity to provide informed consent as assessed by their own clinician
7. Able to complete the required evaluations and take oral medication.
8. Effective contraceptive precautions (either the use of barrier methods or the oral contraceptive pill) to be taken by women of child-bearing age. A negative pregnancy test will be required in order to meet inclusion criteria.

Exclusion Criteria:

1. Prior history of intolerance or serious side effects to Sodium Benzoate or N-acetylcystine.
2. Concomitant use of Ascorbic acid
3. Active substance abuse (except nicotine or caffeine) or dependence within the last three months according to DSM-V criteria.
4. Relevant CNS or other medical disorders.
5. Pregnant or breast feeding
6. Diagnosis of Moderate to Severe Learning Disability
7. Relevant current or past haematological, hepatic, renal, neurological or other medical disorder in the opinion of the principal investigator (PI) or the responsible clinician, that may interfere with the trial.

Primary outcomes:
measure: Feasibility of intervention ( including recruitment rates and drop outs)
timeFrame: Recruitment within 12 months of study start start date
Secondary outcomes:
measure: Overall improvement in symptoms using the Positive and Negative Syndrome Scale (PANSS) total score
timeFrame: change in scores from Baseline to 12 weeks
Other outcomes:
measure: Improvement in positive and/or negative symptoms subscales measured using the PANSS.
timeFrame: change in scores from Baseline to 12 weeks
measure: Improvement on Clinical Global Impression (CGI) Scale and Social and Occupational Functioning Assessment (SOFA) scales.
timeFrame: change in scores from Baseline to 12 weeks
measure: Improvement in cognitive functioning as measured using CogState Schizophrenia Battery.
timeFrame: change in scores from Baseline to 12 weeks
Locations:
city: Quetta
country: Pakistan
facility: Balochistan Institute of Behavioral Science
state: Balochistan
city: Rawalpindi
country: Pakistan
facility: Institute of Psychiatry, Rawalpindi
state: Islamabad
city: Karachi
country: Pakistan
facility: Abbasi Shaheed Hsopital
state: Sindh
city: Karachi
country: Pakistan
facility: Civil Hospital Karachi
state: Sindh
city: Karachi
country: Pakistan
facility: Karwan e Hayat
state: Sindh
Study officials:
affiliation: Ziauddin Hospital
name: Imran B Chaudhry, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI. N-acetyl cysteine as a glutathione precursor for schizophrenia--a double-blind, randomized, placebo-controlled trial. Biol Psychiatry. 2008 Sep 1;64(5):361-8. doi: 10.1016/j.biopsych.2008.03.004. Epub 2008 Apr 23.
citation: Chaudhry IB, Husain N, Drake R, Dunn G, Husain MO, Kazmi A, Hamirani MM, Rahman R, Stirling J, Deakin W. Add-on clinical effects of simvastatin and ondansetron in patients with schizophrenia stabilized on antipsychotic treatment: pilot study. Ther Adv Psychopharmacol. 2014 Jun;4(3):110-6. doi: 10.1177/2045125313511487.
citation: Farokhnia M, Azarkolah A, Adinehfar F, Khodaie-Ardakani MR, Hosseini SM, Yekehtaz H, Tabrizi M, Rezaei F, Salehi B, Sadeghi SM, Moghadam M, Gharibi F, Mirshafiee O, Akhondzadeh S. N-acetylcysteine as an adjunct to risperidone for treatment of negative symptoms in patients with chronic schizophrenia: a randomized, double-blind, placebo-controlled study. Clin Neuropharmacol. 2013 Nov-Dec;36(6):185-92. doi: 10.1097/WNF.0000000000000001.
citation: Lane HY, Lin CH, Green MF, Hellemann G, Huang CC, Chen PW, Tun R, Chang YC, Tsai GE. Add-on treatment of benzoate for schizophrenia: a randomized, double-blind, placebo-controlled trial of D-amino acid oxidase inhibitor. JAMA Psychiatry. 2013 Dec;70(12):1267-75. doi: 10.1001/jamapsychiatry.2013.2159.
citation: Lin CH, Lin CH, Chang YC, Huang YJ, Chen PW, Yang HT, Lane HY. Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial. Biol Psychiatry. 2018 Sep 15;84(6):422-432. doi: 10.1016/j.biopsych.2017.12.006. Epub 2017 Dec 26.
citation: Chaudhry IB, Hallak J, Husain N, Minhas F, Stirling J, Richardson P, Dursun S, Dunn G, Deakin B. Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment. J Psychopharmacol. 2012 Sep;26(9):1185-93. doi: 10.1177/0269881112444941. Epub 2012 Apr 23.