Famotidine in Schizophrenia

Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia

Objective of the trial is to study if famotidine add-on treatment is more effective than placebo add-on in reducing symptoms of schizophrenia among patients receiving insufficient response to ongoing antipsychotic treatment.

Study Overview

• Status: Unknown
• Conditions: Schizophrenia
• Intervention / Treatment: Drug: Placebo; Drug: Famotidine

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jesper Ekelund, MD,PhD; Phone Number: +358503317987; Email: jesper.ekelund@helsinki.fi

Study Locations

• Finland
  • Helsinki, Finland
    • Recruiting
    • Helsinki University Central Hospital Psychiatry Centre
    • Contact: Jesper Ekelund, MD, PhD; Email: jesper.ekelund@helsinki.fi
    • Sub-Investigator: Grigori Joffe, MD, PhD
    • Principal Investigator: Jesper Ekelund, MD,PhD
    • Sub-Investigator: Katarina Meskanen, MSc
    • Sub-Investigator: Roope Heikkila, MSc
  • Helsinki, Finland
    • Active, not recruiting
    • Helsinki University
  • Helsinki, Finland
    • Recruiting
    • Social services and Healthcare, City of Helsinki
    • Principal Investigator: Leena Turpeinen, MD
  • Hyvinkää, Finland
    • Recruiting
    • Kellokoski Hospital
    • Contact: Viacheslav Terevnikov, MD, PhD
    • Principal Investigator: Viacheslav Terevnikov, MD, PhD
• Sweden
  • Stockholm, Sweden, 17177
    • Recruiting
    • Karolinska Institutet
    • Contact: Jari Tiihonen, MD, PhD; Email: jari.tiihonen@ki.se
    • Principal Investigator: Jari Tiihonen, MD, PhD
  • Stockholm, Sweden
    • Recruiting
    • Norra Stockholms Psykiatri, Stockholm County Council
    • Principal Investigator: Christina Lagerbäck, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ICD-10 diagnosis of schizophrenia (F20.00-20.39, F20.5, F20.9) who have had the disorder for at least 5 years and who are on disability pension. (This means that their treatment response is not satisfactory and for the purpose of this study, the subjects are potentially treatment resistant).
• Clinical Global Impression (CGI) severity score of at least 3.
• No changes in schizophrenia treatment within 12 weeks before study inclusion.
• Written informed consent
• The subjects must fulfil schizophrenia criteria both according to DSM- IV (295.10, .20, .30, .60, .90) (American Psychiatric association) and the Research Diagnostic Criteria for schizophrenia (RDC) [40]. They must also have at least mild residual symptoms (CGI 3 points). The DSM-IV diagnosis will be verified by use of the SCID-I [41]. The DSM-IV is clearly the most commonly used in psychiatric research, so this is important to be able to generalize the findings. However, several previous studies have used the RDC, so to be able to compare the results, we will diagnose the patients according to both systems.
• Women of child-bearing age will be included only of they use adequate contraception, or if we can otherwise verify that the subject is not pregnant (s-HCG), the possibility of pregnancy is negligible (e.g. the personnel of the housing facility reports that the person has not had sexual relationships for years) and the subject approves to remain sexually abstinent for the duration of the study.

Exclusion Criteria:

• Epilepsy or a history of unclear seizures, stroke, Parkinson's disease, AIDS
• History of substance addiction or abuse within 3 months prior to enrolment.
• Individuals who are deemed at risk for aggressive behaviour or suicide
• If their laboratory tests, EKG or other clinical observation warrants exclusion, they will be excluded
• Women who are pregnant or breast-feeding subjects will not be included in the study.
• Patients with any serious unstable physical illness will also be excluded
• Patients who have been deemed to be legally incapacitated according to Finnish or Swedish law.
• Regular Uuse of H2-antagonists as prescribed by a physician.
• Known allergy to famotidine or any other component of interventional drug will be excluded.
• Ongoing treatment with clozapine and dixyrazine.
• Clinical condition "very much improved" or "much improved", assessed by CGI, during the placebo lead-in
• Renal insufficiency (P-creatinine not within normal range. Glomerular filtration rate <30 ml/min according to the Cockcroft-Gault formula. )
• Liver insufficiency (S-ALAT elevated more than 2-fold above the laboratory specific normal range)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo control	Drug: Placebo
Experimental: Famotidine; Famotidine 100mg x 2 orally	Drug: Famotidine; 100mg x 2 p.o.; Other Names: Famotidine Hexal; SUB07503MIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Positive and Negative Syndrome Scale (PANSS) at 8 weeks	In addition PANSS ratings are done at screening, every two weeks during treatment and two weeks after end of treatment.	Rating at start of treatment (0 weeks) and at end of treatment (8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in Clinical Global Impression (CGI) scale at 8 weeks	In addition CGI ratings are done at screening, every two weeks during treatment and two weeks after end of treatment.	Rating at start of treatment (0 weeks) and at end of treatment (8 weeks)
Change from Baseline in Calgary Depression Scale (CDS) at 8 weeks		Rating at start of treatment (0 weeks) and at end of treatment (8 weeks)
Change from Baseline in The Overall Anxiety Severity and Impairment Scale (OASIS)at 8 weeks		Rating at start of treatment (0 weeks) and at end of treatment (8 weeks)
Change from Baseline in CogState scores at 8 weeks	A standardized, language independent computerized battery of cognitive tests (CogState®). This battery has been validated and shown to be a sensitive indicator of mild impairments in the following cognitive domains: psychomotor speed, attention, working memory and episodic learning and memory.	Rating at start of treatment (0 weeks) and at end of treatment (8 weeks)
Change from baseline in nightly sleep duration measured with actigraphy at 8 weeks	Average nightly sleep duration of seven nights before and after intervention measured with an actigraph	Measurement at start of treatment (0 weeks) and at end of treatment (8 weeks)

Collaborators and Investigators

• Sponsor: Jesper Ekelund
• Collaborators: Karolinska Institutet; Stanley Medical Research Institute; Region Stockholm; City of Helsinki; Ahokas foundation, Finland
• Investigators: Principal Investigator: Jesper Ekelund, MD, PhD, University of Helsinki

Publications and helpful links

General Publications

• Meskanen K, Ekelund H, Laitinen J, Neuvonen PJ, Haukka J, Panula P, Ekelund J. A randomized clinical trial of histamine 2 receptor antagonism in treatment-resistant schizophrenia. J Clin Psychopharmacol. 2013 Aug;33(4):472-8. doi: 10.1097/JCP.0b013e3182970490.

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Anticipated): August 1, 2016
• Study Completion (Anticipated): August 1, 2016

Study Registration Dates

• First Submitted: August 23, 2013
• First Submitted That Met QC Criteria: September 18, 2013
• First Posted (Estimate): September 19, 2013

Study Record Updates

• Last Update Posted (Estimate): April 14, 2015
• Last Update Submitted That Met QC Criteria: April 13, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Gastrointestinal Agents; Anti-Ulcer Agents; Histamine Antagonists; Histamine Agents; Histamine H2 Antagonists; Famotidine
• Other Study ID Numbers: 2012-005513-40