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Minocycline, Acetylsalicylic Acid or Pramipexole vs Placebo in Patients With Schizophrenia or Schizoaffective Disorder (MAP-S-01)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Sheba Medical Center.
Recruitment status was  Not yet recruiting
Sponsor:
Information provided by:
Sheba Medical Center
ClinicalTrials.gov Identifier:
NCT01320982
First received: February 2, 2011
Last updated: March 22, 2011
Last verified: March 2011
  Purpose

The objective of the study is to evaluate the efficacy of Pramipexole, Minocycline and Aspirin compared to placebo, as add-on to anti-psychotics in the treatment of patients with schizophrenia.


Condition Intervention Phase
Schizophrenia
Schizoaffective Disorder
Drug: minocycline
Drug: pramipexole
Drug: acetylsalicylic acid
Drug: placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Trial Administering Minocycline, Acetylsalicylic Acid or Pramipexole vs Placebo as add-on to Antipsychotics in Patients With Schizophrenia or Schizoaffective Disorder

Resource links provided by NLM:


Further study details as provided by Sheba Medical Center:

Primary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS)total score [ Time Frame: Positive and Negative Syndrome Scale (PANSS) total score at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS)total score at 8 weeks

  • Positive and Negative Syndrome Scale (PANSS)total score [ Time Frame: Positive and Negative Syndrome Scale (PANSS) total score at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS)total score at 16 weeks.


Secondary Outcome Measures:
  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS)positive sub-scale score at week 2 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and negative syndrome scale(PANSS) positive sub-scale scoreat 2 weeks.

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale(PANSS) positive sub-scale score at week 4 . ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale(PANSS) positive sub-scale score at 4 weeks.

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and negative syndrome scale(PANSS) positive sub-scale score at week 8. ] [ Designated as safety issue: No ]
    Change from baseline in Positive and negative syndrome scale(PANSS) positive sub-scale score at 8 weeks.

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and negative syndrome scale(PANSS) positive sub-scale score at week 16. ] [ Designated as safety issue: No ]
    Change from baseline in Positive and negative syndrome scale(PANSS) positive sub-scale score at 16 weeks.

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at week 2 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at 2 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at week 4 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at 4 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at 8 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) negative sub-scale score at 16 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at 2 weeks ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at week 2

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at week 4 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at 4 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at 8 weeks

  • Positive and Negative Syndrome Scale (PANSS) [ Time Frame: Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Positive and Negative Syndrome Scale (PANSS) general psychopathology sub-scale score at 16 weeks

  • Clinical Global Impression Scale-Severity (CGI-S) [ Time Frame: Clinical Global Impression Scale-Improvement (CGI-S) at week 2 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale-Severity(CGI-S)at 2 weeks

  • Clinical Global Impression Scale-Severity (CGI-S) [ Time Frame: Clinical Global Impression Scale-Severity (CGI-S) at week 5 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale-Severity(CGI-S)at 5 weeks

  • Clinical Global Impression Scale-Severity(CGI-S) [ Time Frame: linical Global Impression Scale-Severity(CGI-S) at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale-Severity(CGI-S)at 8 weeks

  • Clinical Global Impression Scale-Severity(CGI-S) [ Time Frame: Change from baseline in Clinical Global Impression Scale-Severity(CGI-S) at week 12 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale-Severity(CGI-S)at 12 weeks

  • Clinical Global Impression Scale-Severity(CGI-S) [ Time Frame: Change from baseline in Clinical Global Impression Scale-Severity(CGI-S) at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale-Severity(CGI-S)at 16 weeks

  • Clinical Global Impression Scale- Improvement (CGI-I) [ Time Frame: Clinical Global Impression Scale- Improvement (CGI-I) at week 2 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale- Improvement (CGI-I)at 2 weeks

  • Clinical Global Impression Scale- Improvement (CGI-I) [ Time Frame: Clinical Global Impression Scale- Improvement (CGI-I) at week 5 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale- Improvement (CGI-I)at 5 weeks

  • Clinical Global Impression Scale- Improvement (CGI-I) [ Time Frame: Clinical Global Impression Scale- Improvement (CGI-I)at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale- Improvement (CGI-I)at 8 weeks

  • Clinical Global Impression Scale- Improvement (CGI-I) [ Time Frame: Clinical Global Impression Scale- Improvement (CGI-I) at week 12 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale- Improvement (CGI-I)at 12 weeks

  • Clinical Global Impression Scale- Improvement (CGI-I) [ Time Frame: Clinical Global Impression Scale- Improvement (CGI-I)at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Clinical Global Impression Scale- Improvement (CGI-I)at 16 weeks

  • Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: rief Assessment of Cognition in Schizophrenia (BACS)at week 8 ] [ Designated as safety issue: No ]
    Change from baseline in Brief Assessment of Cognition in Schizophrenia (BACS)at 8 weeks.

  • Brief Assessment of Cognition in Schizophrenia (BACS) [ Time Frame: Brief Assessment of Cognition in Schizophrenia (BACS)at week 16 ] [ Designated as safety issue: No ]
    Change from baseline in Brief Assessment of Cognition in Schizophrenia (BACS)at 16 weeks.


Estimated Enrollment: 400
Study Start Date: March 2011
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: minocycline
minocycline
Drug: minocycline
minocycline 100 mg/bid
Active Comparator: pramipexole
pramipexole
Drug: pramipexole
pramipexole 0.125, 0.25, 0.5 and 0.75 mg/bid
Active Comparator: acetylsalicylic acid
acetylsalicylic acid
Drug: acetylsalicylic acid
acetylsalicylic acid 500mg/ bid
Placebo Comparator: Placebo
Placebo
Drug: placebo
placebo bid

Detailed Description:

Inflammatory processes have been implicated as a cause of schizophrenia (Fan, Goff et al. 2007), and the COX-2 inhibitor, Celecoxib, has been shown to reduce symptoms of schizophrenia (Muller, Krause et al. 2010). Aspirin, which is also a non-steroidal anti-inflammatory drug(NSAID), irreversibly inhibits Cyclooxygenase-1 (COX-1) and modifies the enzymatic activity of Cyclooxygenase-2 (COX-2), thus inhibiting the formation of prostaglandins and reduces inflammatory reaction. In a study funded by the Stanley Medical Research Institute (SMRI) recently published, Laan at all (Laan, Grobbee et al. 2010) administered add-on 1000mg/d of Aspirin to patients with schizophrenia receiving anti-psychotics, and reported reductions in Positive and negative syndrome scale (PANSS) total and PANSS positive scores without substantial side effects.

Minocycline is a second-generation tetracycline that exerts anti-inflammatory and antimicrobial effects while having a distinct neuroprotective profile. Minocycline effects the glutaminergic system, through inhibition of neuronal nitric oxide synthase (nNOS) and blocking of nitric oxide (NO)- induced neurotoxicity (Du et al, 1998; Jiang et al., 2005), and thus has been suggested as a potential treatment for schizophrenia. One published study (Levkovitz, Mendlovich et al. 2010), and another, unpublished study by Bill Deakin found that add-on treatment of 200mg/d of Minocycline was beneficial for symptoms and cognition in schizophrenia, and a study by Miayoka et al (Miyaoka, Yasukawa et al. 2008) administered open-label 450 mg/day Minocycline, and found improvement on positive symptoms.

Indirect pharmacological evidence suggests a relative excess of dopaminergic activity as being implicated in the pathogenesis of some of the symptoms of schizophrenia, and all effective antipsychotics effect dopamine D2 receptors. Pramipexole is a pre-synaptic dopamine auto-receptor agonist hypothesized to improve in symptoms in schizophrenia patients. In an open label study, Kasper at all (Kasper, Barnas et al. 1997) showed statistically significant improvement in PANSS scores in patients not stabilized on haloperidol. Other data indicate that add-on Pramipexole improves symptoms of depression and cognition, in patients with affective disorders (Goldberg, Frye et al. 1999; Sporn, Ghaemi et al. 2000; Goldberg, Burdick et al. 2004; Zarate, Payne et al. 2004), and Malhotra et al, unpublished data.

All of these studies were relatively small, and were performed by investigators with an interest in the compound. The objective of this study is to replicate them in large trial by investigators with no specific interest in the compounds. This proposed study is a multi-arm study, in which patients will be randomized to one of the three study drugs: Pramipexole, Minocycline and Aspirin, or placebo as part of the same protocol. A design by which several active compounds are all compared to the same placebo arm has been utilized before for schizophrenia (Meltzer, Arvanitis et al. 2004). This design has several advantages: in addition to reduced costs and time it exposes fewer patients to placebo, and enables direct comparison between the compounds and not only to the placebo.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, 18-65 years of age, inclusive
  2. Females who are abstinent or practicing an established method of birth control (oral contraceptive tablets, hormonal implant device, hormone patch, injectable contraceptive, intrauterine device.
  3. Willing and able to provide informed consent, after the nature of the study has been fully explained
  4. Current DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder as confirmed by modified Structured Clinical Interview for DSM Disorders (SCID) and having had at least 2 prior schizophrenic episodes, or continually ill for at least 6 months.
  5. Symptoms: 4 (moderate) or above on Clinical Global Impression scale (CGI-S)and 4 (moderate)or above score on two of the following four Positive and negative syndrome scale (PANSS) items: delusions, hallucinatory behaviors, conceptual disorganization or suspiciousness/ persecution, and/or a total PANSS negative symptoms score of 18.
  6. Must be on any antipsychotic drug, for at least 2 weeks prior to the baseline visit, at doses within the Patient Outcome Research Team (PORT) criteria, whenever possible. Patients receiving higher doses will have their records reviewed to insure that their dose is required and, if possible, will be stabilized on a lower dose prior to study entry.
  7. Inpatients or outpatients. Inpatients will be randomized 3 days or more after admission

Exclusion Criteria:

  1. Unwilling or unable, in the opinion of the Investigator, to comply with study instructions
  2. Pregnant or breast-feeding
  3. Unstable medical disease (malignancy, poorly controlled diabetes, active ischemic cardiac disease, or cardiomyopathy, serious pulmonary disease, kidney disease, impaired liver functioning. History of hemorrhagic CVA or peptic ulcer disease.
  4. Patients treated with: any of the trial medications i.e. pramipexole/minocycline/ acetylsalicylic acid, NSAIDs, anti-coagulants, sucralfate, cimetidine, amantadine, mexiletine.
  5. Likely allergy or sensitivity to raloxifene/pramipexole/minocycline/acetylsalicylic acid.
  6. At significant risk of committing suicide, or in the opinion of the Investigator, currently is at imminent risk of suicide or harming others.
  7. Patients with a current DSM-IV substance or alcohol abuse. Patients with a history of and/or current recreational use of cannabinoids or alcohol, and/or patients who smoke cigarettes can be included.
  8. Concurrent delirium, mental retardation, drug-induced psychosis, or history of clinically significant brain trauma documented by CT or MRI.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01320982

Contacts
Contact: Mark Weiser, MD 972-52-6666575 mweiser@netvision.net.il
Contact: Katya Rubinstein, MA 972-3-5303454 rubins.katya@gmail.com

Locations
Israel
Sheba Medical Center Not yet recruiting
Ramat-Gan, Israel, 52621
Contact: Mark Weiser, MD    +972-52-6666575    mweiser@netvision.net.il   
Contact: Katya Rubinstein, MA    +972-3-5303454    rubins.katya@gmail.com   
Principal Investigator: Mark Weiser, MD         
Romania
Clinica de Psihiatrie Not yet recruiting
Arad, Romania
Contact: Delia Podea, MD    0722 583 757    deliapodea@gmail.com   
Principal Investigator: Delia Podea, MD         
Spitalul de Psihiatrie Botosani, Sectia Psihiatrie Not yet recruiting
Botosani, Romania
Contact: Nicolae Vlad, MD    0741 335 034    v_nicolae@yahoo.com   
Principal Investigator: Nicolae Vlad, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Maria Ladea, MD    0724 371 042    marialadea@gmail.com   
Principal Investigator: Maria Ladea, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Valentin Matei, MD    0723 640 918    petcu_camelia@yahoo.com   
Principal Investigator: Valentin Matei, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Maria-Silvia Trandafir, MD    0724 275 572    silviatrandafir2004@yahoo.com   
Principal Investigator: Maria-Silvia Trandafir, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Ana-Liana Giurgiuca, MD    0722 378 967    giurgiuca_liana@yahoo.com   
Principal Investigator: Ana-Liana Giurgiuca, Md         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Gabriela Marian, MD    0723 569 620    gabi.marian@yahoo.com   
Principal Investigator: Marian Gabriela, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Dorina-Valerica Sima, MD    0723 859 570    dorinasima@yahoo.com   
Principal Investigator: Dorina-Valerica Sima, MD         
Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia" Not yet recruiting
Bucuresti, Romania
Contact: Dan Prelipceanu, MD    0722 300 227    prelipceanudan@yahoo.com   
Principal Investigator: Dan Prelipceanu, MD         
Sp. Jud. "Prof. Dr.O. Fodor" Not yet recruiting
Cluj-Napoca, Romania
Contact: Mircea-Alexandru Birt, MD    0721 012 220    mirceabirt@yahoo.com   
Principal Investigator: Mircea-Alexandru Birt, MD         
Spitalul Clinic Judetean de Urgenta Cluj Not yet recruiting
Cluj-Napoca, Romania
Contact: Ioana-Valentina Miclutia, MD    0722 796 067    ioanamiclu@yahoo.com   
Principal Investigator: Ioana-Valentina Miclutia, MD         
Spitalul Clinic de Psihiatrie Socola, Iasi Not yet recruiting
Iasi, Romania
Contact: Nicoleta Cartas, MD    0724 576 261    nicoletacartas_socola@yahoo.com   
Principal Investigator: Nicoleta Cartas, MD         
Spitalul Clinic de Psihiatrie Socola, Iasi Not yet recruiting
Iasi, Romania
Contact: Serban Turliuc, MD    0745 203 002    serban_turliuc@yahoo.com   
Principal Investigator: Serban Turliuc, MD         
Sponsors and Collaborators
Sheba Medical Center
Investigators
Principal Investigator: Mark Weiser, MD Sheba Medical Center
  More Information

No publications provided

Responsible Party: Mark Weiser MD (PI), Sheba Medical Center
ClinicalTrials.gov Identifier: NCT01320982     History of Changes
Other Study ID Numbers: SHEBA-8273-10-MW-CTIL
Study First Received: February 2, 2011
Last Updated: March 22, 2011
Health Authority: Israel: Israeli Health Ministry Pharmaceutical Administration

Keywords provided by Sheba Medical Center:
Schizophrenia
schizoaffective disorder

Additional relevant MeSH terms:
Disease
Psychotic Disorders
Schizophrenia
Mental Disorders
Pathologic Processes
Schizophrenia and Disorders with Psychotic Features
Aspirin
Minocycline
Pramipexole
Analgesics
Analgesics, Non-Narcotic
Anti-Bacterial Agents
Anti-Dyskinesia Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antioxidants
Antiparkinson Agents
Antipyretics
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Dopamine Agents
Dopamine Agonists
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 24, 2014