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

Schizophrenia Clinical Trial

Official title:

Minocycline add-on Medication to Antipsychotics in the Treatment of Schizophrenia Patients: A Double- Blind Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02907437
• Other study ID #: 519
• Status: Recruiting
• Phase: Phase 3
• First received: September 16, 2016
• Last updated: September 19, 2016
• Start date: January 2015
• Est. completion date: January 2018

Study information

• Verified date: September 2016
• Source: Beer Yaakov and Ness Ziona Mental Health Center
• Contact: Rafael Stryjer, MD
• Phone: +528612945
• Email: rafael.stryjer[@]beerness.health.gov.il
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: January 2018
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Men and women 18-60 years of age.

2. 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.

3. Initiated on treatment with stable dosage (within +/- 25%) of atypical anti-psychotic medication for at least 6 weeks.

4. Capable and willing to provide informed consent.

5. Able to adhere to the treatment schedule.

6. Able to read, hear, write and speak the local language.

7. Has signed a written informed consent to participate in the study.

Exclusion Criteria:

1. Patients with acute, unstable, or decompensated medical condition.

2. Present substance abuse.

3. Major depression (MDD) diagnosis.

4. Attention deficit/ hyperactivity disorder (ADHD/ADD) diagnosis.

5. Cognitive dysfunction, such as Alzheimer disease or retardation.

6. Acute psychotic state.

7. Aggressive or violent patient or with vast history of aggressive or violent behavior.

8. Diagnosis of Borderline/ Anti Social/ Narcissistic personality disorders.

9. Previous sensitivity to Minocycline.

10. Current suicidal ideation or history of a suicide attempt in the past three years

11. 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.

12. Subjects who are taking a known contraindication to Minocycline treatment (anti-coagulants, other antibiotics (of the penicillin group), methoxyflurane, Isotretinoin).

13. Subjects who had received treatment with Minocycline or ß-lactam antibiotics in the preceding half year before study entry.

14. Subjects who are under compulsory hospitalization.

15. Subjects with medical history of Intestinal disease, Peptic ulcer or gastritis.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neurobehavioral Manifestations
• Schizophrenia

Intervention

Drug:
• Minocycline
Minocycline as an add-on drug (200 mg/day)
• Placebo
(200 mg/day)

Other:
• Probiotics
(450 mg/day)

Locations

Country	Name	City	State
Israel	Bees Yaakov and Ness Ziona Mental Health Center	Beer Yaakov

Sponsors (2)

Lead Sponsor	Collaborator
Beer Yaakov and Ness Ziona Mental Health Center	Bar-Ilan University, Israel

Country where clinical trial is conducted

Israel, 

References & 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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Meyer U, Schwarz MJ, Müller 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. — View Citation

Monji A, Kato T, Kanba S. Cytokines and schizophrenia: Microglia hypothesis of schizophrenia. Psychiatry Clin Neurosci. 2009 Jun;63(3):257-65. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Positive and Negative Syndrome Scale (PANSS)		Change in PANSS scores over the 6-weeks study	No
Primary	Scale for Assessment of Negative Symptoms (SANS)		Change in SANS scores over the 6-weeks study	No
Secondary	Clinical Global Impressions (CGI)		Change in CGI scores over the 6-weeks study	No
Secondary	The Montreal Cognitive Assessment (MoCa) task		Change in MoCa scores over the 6-weeks study	No
Secondary	Trail making task (TMT)		Change in TMT scores over the 6-weeks study	No
Secondary	Empathy Cartoon task		Change in Empathy Cartoon task scores over the 6-weeks study	No
Secondary	Interpersonal Reactivity Index (IRI) Questionnaire		Change in IRI scores over the 6-weeks study	No