Minocycline, Acetylsalicylic Acid or Pramipexole vs Placebo in Patients With Schizophrenia or Schizoaffective Disorder

NCT ID: NCT01320982

Last Updated: 2011-03-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-03-31

Study Completion Date

2012-07-31

Brief Summary

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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.

Detailed Description

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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 One published study (Levkovitz, Mendlovich et al. 2010), and another, unpublished study by Bill Deakin found that add-on treatment of 200mg/d of Minocycline was beneficial for symptoms and cognition in schizophrenia, and a study by Miayoka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.

Conditions

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Schizophrenia Schizoaffective Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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minocycline

minocycline

Group Type ACTIVE_COMPARATOR

minocycline

Intervention Type DRUG

minocycline 100 mg/bid

pramipexole

pramipexole

Group Type ACTIVE_COMPARATOR

pramipexole

Intervention Type DRUG

pramipexole 0.125, 0.25, 0.5 and 0.75 mg/bid

acetylsalicylic acid

acetylsalicylic acid

Group Type ACTIVE_COMPARATOR

acetylsalicylic acid

Intervention Type DRUG

acetylsalicylic acid 500mg/ bid

Placebo

Placebo

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

placebo bid

Interventions

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minocycline

minocycline 100 mg/bid

Intervention Type DRUG

pramipexole

pramipexole 0.125, 0.25, 0.5 and 0.75 mg/bid

Intervention Type DRUG

acetylsalicylic acid

acetylsalicylic acid 500mg/ bid

Intervention Type DRUG

placebo

placebo bid

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sheba Medical Center

OTHER_GOV

Sponsor Role lead

Responsible Party

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Sheba Medical Center

Principal Investigators

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Mark Weiser, MD

Role: PRINCIPAL_INVESTIGATOR

Sheba Medical Center

Locations

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Sheba Medical Center

Ramat Gan, , Israel

Site Status

Clinica de Psihiatrie

Arad, , Romania

Site Status

Spitalul de Psihiatrie Botosani, Sectia Psihiatrie

Botoșani, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Spitalul Clinic de Psihiatrie "Prof. Dr. Alex. Obregia"

Bucharest, , Romania

Site Status

Sp. Jud. "Prof. Dr.O. Fodor"

Cluj-Napoca, , Romania

Site Status

Spitalul Clinic Judetean de Urgenta Cluj

Cluj-Napoca, , Romania

Site Status

Spitalul Clinic de Psihiatrie Socola, Iasi

Iași, , Romania

Site Status

Spitalul Clinic de Psihiatrie Socola, Iasi

Iași, , Romania

Site Status

Countries

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Israel Romania

Central Contacts

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Mark Weiser, MD

Role: CONTACT

972-52-6666575

Katya Rubinstein, MA

Role: CONTACT

972-3-5303454

Facility Contacts

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Mark Weiser, MD

Role: primary

+972-52-6666575

Katya Rubinstein, MA

Role: backup

+972-3-5303454

Delia Podea, MD

Role: primary

0722 583 757

Nicolae Vlad, MD

Role: primary

0741 335 034

Dan Prelipceanu, MD

Role: primary

0722 300 227

Gabriela Marian, MD

Role: primary

0723 569 620

Maria Ladea, MD

Role: primary

0724 371 042

Dorina-Valerica Sima, MD

Role: primary

0723 859 570

Maria-Silvia Trandafir, MD

Role: primary

0724 275 572

Ana-Liana Giurgiuca, MD

Role: primary

0722 378 967

Valentin Matei, MD

Role: primary

0723 640 918

Mircea-Alexandru Birt, MD

Role: primary

0721 012 220

Ioana-Valentina Miclutia, MD

Role: primary

0722 796 067

Serban Turliuc, MD

Role: primary

0745 203 002

Nicoleta Cartas, MD

Role: primary

0724 576 261

References

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Levi L, Zamora D, Nastas I, Gonen I, Radu P, Matei V, Ciobanu AM, Nacu A, Boronin L, Karakrah L, Davidson M, Davis JM, Weiser M. Add-On Pramipexole for the Treatment of Schizophrenia and Schizoaffective Disorder: A Randomized Controlled Trial. J Clin Psychiatry. 2022 Aug 1;83(5):21m14233. doi: 10.4088/JCP.21m14233.

Reference Type DERIVED
PMID: 35921506 (View on PubMed)

Weiser M, Zamora D, Levi L, Nastas I, Gonen I, Radu P, Matei V, Nacu A, Boronin L, Davidson M, Davis JM. Adjunctive Aspirin vs Placebo in Patients With Schizophrenia: Results of Two Randomized Controlled Trials. Schizophr Bull. 2021 Jul 8;47(4):1077-1087. doi: 10.1093/schbul/sbaa198.

Reference Type DERIVED
PMID: 33479775 (View on PubMed)

Other Identifiers

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SHEBA-8273-10-MW-CTIL

Identifier Type: -

Identifier Source: org_study_id

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