Minocycline add-on to Antipsychotics for the Treatment of Negative and Cognitive Symptoms in Schizophrenia

NCT02907437 | Unknown Phase 3

• 1 other identifier: 519
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Current medications have only a limited effect on two core symptoms of schizophrenia, negative symptoms and cognitive deficits. Minocycline is a second-generation tetracycline which has a beneficial effect in various neurological disorders. In the past years, various findings from clinical studies showed its potential role for the treatment of these symptoms of schizophrenia. The current study aims to examine the efficacy of minocycline as add-on treatment for alleviating positive, negative and cognitive symptoms in schizophrenia patients.The current study is a single center, double-blind, randomized study that assess the adjuvant therapeutic effect of minocycline vs. placebo added to antipsychotic medications, in adult patients suffering from schizophrenia. Patients will be recruited and randomly allocated to a minocycline or placebo treatment (200 mg/day) for 6 weeks of treatment. In addition, all patients will receive probiotics (450mg/day) in order to prevent any gastrointestinal influences of antibiotics administration. Positive and negative symptoms , as well as cognitive functions will be assessed before and after treatment.

Conditions

Schizophrenia

Keywords

Minocycline; Negative symptoms; Cognitive symptoms; Inflammation

Outcome Measures

Primary Outcomes (2)

• Positive and Negative Syndrome Scale (PANSS)

  Change in PANSS scores over the 6-weeks study

• Scale for Assessment of Negative Symptoms (SANS)

  Change in SANS scores over the 6-weeks study

Secondary Outcomes (5)

• Clinical Global Impressions (CGI)

  Change in CGI scores over the 6-weeks study

• The Montreal Cognitive Assessment (MoCa) task

  Change in MoCa scores over the 6-weeks study

• Trail making task (TMT)

  Change in TMT scores over the 6-weeks study

• Empathy Cartoon task

  Change in Empathy Cartoon task scores over the 6-weeks study

• Interpersonal Reactivity Index (IRI) Questionnaire

  Change in IRI scores over the 6-weeks study

Study Arms (2)

Minocycline treatment

ACTIVE COMPARATOR

Intervention: Drug: Minocycline (200 mg/day)

Drug: Minocycline; Other: Probiotics

Placebo treatment

PLACEBO COMPARATOR

Placebo Intervention: Drug: Placebo (200 mg/day)

Drug: Placebo; Other: Probiotics

Interventions

Minocycline DRUG

Minocycline as an add-on drug (200 mg/day)

Minocycline treatment

Placebo DRUG

(200 mg/day)

Placebo treatment

Probiotics OTHER

(450 mg/day)

Minocycline treatment; Placebo treatment

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Men and women 18-60 years of age.
• Diagnostic and Statistical Manual (DSM) 5 diagnosis of Schizophrenia/ Schizo effective disorder based on the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (SCID) for schizophrenia and confirmed by two senior psychiatrists.
• Initiated on treatment with stable dosage (within +/- 25%) of atypical anti-psychotic medication for at least 6 weeks.
• Capable and willing to provide informed consent.
• Able to adhere to the treatment schedule.
• Able to read, hear, write and speak the local language.
• Has signed a written informed consent to participate in the study.

You may not qualify if:

• Patients with acute, unstable, or decompensated medical condition.
• Present substance abuse.
• Major depression (MDD) diagnosis.
• Attention deficit/ hyperactivity disorder (ADHD/ADD) diagnosis.
• Cognitive dysfunction, such as Alzheimer disease or retardation.
• Acute psychotic state.
• Aggressive or violent patient or with vast history of aggressive or violent behavior.
• Diagnosis of Borderline/ Anti Social/ Narcissistic personality disorders.
• Previous sensitivity to Minocycline.
• Current suicidal ideation or history of a suicide attempt in the past three years
• Known or suspected pregnancy or women of childbearing potential not using a medically accepted form of contraception .(if using oral contraceptives, during the Minocycline treatment, subject should use an additional contraceptives), or women who are breastfeeding.
• Subjects who are taking a known contraindication to Minocycline treatment (anti-coagulants, other antibiotics (of the penicillin group), methoxyflurane, Isotretinoin).
• Subjects who had received treatment with Minocycline or β-lactam antibiotics in the preceding half year before study entry.
• Subjects who are under compulsory hospitalization.
• Subjects with medical history of Intestinal disease, Peptic ulcer or gastritis.

Sponsors & Collaborators

• Beer Yaakov - Ness Ziona Mental Health Center: lead
• Bar-Ilan University, Israel: collaborator

Study Sites (1)

Bees Yaakov and Ness Ziona Mental Health Center

Beer Yaakov, Israel

RECRUITING

Related Publications (10)

• 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.

  PMID: 22526685 BACKGROUND

• Chaves C, de Marque CR, Wichert-Ana L, Maia-de-Oliveira JP, Itikawa EN, Crippa JA, Zuardi AW, Todd KG, Baker GB, Dursun SM, Hallak JE. Functional neuroimaging of minocycline's effect in a patient with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Apr 16;34(3):550-2. doi: 10.1016/j.pnpbp.2010.01.020. Epub 2010 Feb 6. No abstract available.

  PMID: 20138948 BACKGROUND

• Davis MC, Horan WP, Marder SR. Psychopharmacology of the negative symptoms: current status and prospects for progress. Eur Neuropsychopharmacol. 2014 May;24(5):788-99. doi: 10.1016/j.euroneuro.2013.10.010. Epub 2013 Nov 4.

  PMID: 24252823 BACKGROUND

• Dean OM, Data-Franco J, Giorlando F, Berk M. Minocycline: therapeutic potential in psychiatry. CNS Drugs. 2012 May 1;26(5):391-401. doi: 10.2165/11632000-000000000-00000.

  PMID: 22486246 BACKGROUND

• Jhamnani K, Shivakumar V, Kalmady S, Rao NP, Venkatasubramanian G. Successful use of add-on minocycline for treatment of persistent negative symptoms in schizophrenia. J Neuropsychiatry Clin Neurosci. 2013 Winter;25(1):E06-7. doi: 10.1176/appi.neuropsych.11120376. No abstract available.

  PMID: 23487204 BACKGROUND

• Khodaie-Ardakani MR, Mirshafiee O, Farokhnia M, Tajdini M, Hosseini SM, Modabbernia A, Rezaei F, Salehi B, Yekehtaz H, Ashrafi M, Tabrizi M, Akhondzadeh S. Minocycline add-on to risperidone for treatment of negative symptoms in patients with stable schizophrenia: randomized double-blind placebo-controlled study. Psychiatry Res. 2014 Mar 30;215(3):540-6. doi: 10.1016/j.psychres.2013.12.051. Epub 2014 Jan 9.

  PMID: 24480077 BACKGROUND

• Levkovitz Y, Mendlovich S, Riwkes S, Braw Y, Levkovitch-Verbin H, Gal G, Fennig S, Treves I, Kron S. A double-blind, randomized study of minocycline for the treatment of negative and cognitive symptoms in early-phase schizophrenia. J Clin Psychiatry. 2010 Feb;71(2):138-49. doi: 10.4088/JCP.08m04666yel. Epub 2009 Nov 3.

  PMID: 19895780 BACKGROUND

• Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257-65. doi: 10.1111/j.1440-1819.2009.01945.x.

  PMID: 19579286 BACKGROUND

• Lisiecka DM, Suckling J, Barnes TR, Chaudhry IB, Dazzan P, Husain N, Jones PB, Joyce EM, Lawrie SM, Upthegrove R, Deakin B. The benefit of minocycline on negative symptoms in early-phase psychosis in addition to standard care - extent and mechanism (BeneMin): study protocol for a randomised controlled trial. Trials. 2015 Mar 2;16:71. doi: 10.1186/s13063-015-0580-x.

  PMID: 25886254 BACKGROUND

• Meyer U, Schwarz MJ, Muller N. Inflammatory processes in schizophrenia: a promising neuroimmunological target for the treatment of negative/cognitive symptoms and beyond. Pharmacol Ther. 2011 Oct;132(1):96-110. doi: 10.1016/j.pharmthera.2011.06.003. Epub 2011 Jun 15.

  PMID: 21704074 BACKGROUND

MeSH Terms

Conditions

Schizophrenia; cyclopia sequence; Neurobehavioral Manifestations; Inflammation

Interventions

Minocycline; Probiotics

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Pathologic Processes

Intervention Hierarchy (Ancestors)

Tetracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Rafael Stryjer, MD

  Beer Yaakov - Ness Ziona Mental Health Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rafael Stryjer, MD

CONTACT

+528612945; rafael.stryjer@beerness.health.gov.il

Netali Mor, MA

CONTACT

+972524207260; netalimor@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Psychatrist

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: September 20, 2016
• Study Start: January 1, 2015
• Primary Completion: February 1, 2017
• Study Completion: January 1, 2018
• Last Updated: September 20, 2016

Record last verified: 2016-09

Locations

IL (1)