Official Title: “Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia”

The purpose of the study is to investigate whether blockade of the histamine H2 receptors in the brain will have any beneficial effect on the symptoms of subjects with schizophrenia.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2009

Histamine functions as a neurotransmitter in the brain. It has an important role as modulator of the release of other neurotransmitters, including dopamine.

The histamine receptors are widely expressed in the brain, H1 and H2 receptors are post-synaptic, H3 a pre-synaptic autoreceptor. There is an abundance of neurobiologic data from animal and human studies supporting the role of histamine in the pathogenesis and treatment of psychoses.

In 1990 a case report of a treatment resistant subject with schizophrenia whos symptoms improved markedly when he was prescribed a H2 antagonist because of peptic ulcer. Later, a open-label trial including 18 patients has been performed, reporting significant symptom reduction, especially on negative symptoms. Also the subjective comments both by the subjects and the investigators in that study were optimistic and suggested an effect primarily on negative symptoms.

The present study will be the first double-blind, randomized, placebo controlled, parallel group study of the subject matter. The study focuses on treatment resistant schizophrenia cases in the stable phase.

Intervention(s) in this Clinical Trial

• Drug: famotidine
  • capsules containing 100 mg of famotidine p.o., twice daily for 4 weeks
• Drug: Placebo
  • Placebo administered in identical capsules as the experimental drug.

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
• Placebo Comparator: 2

Primary Measures

• Scale for the Assessment of Negative Symptoms (SANS) score
  • Time Frame: 5 weeks
    Safety Issue?: No

Secondary Measures

• Positive and Negative Syndrome Scale (PANSS) score
  • Time Frame: 5 weeks
    Safety Issue?: No
• Clinical Global Impression (CGI) score
  • Time Frame: 5 weeks
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of schizophrenia assessed by SCID-I (DSM-IV) as well as RDC-criteria
• Patient record mention of schizophrenia (ICD-10) at least 5 years previously
• Disability pension due to psychiatric disorder
• At least 3 points on the CGI scale

Exclusion Criteria:

• Epilepsy or a history of unclear seizures
• Stroke
• Parkinson's disease
• AIDS
• Substance addiction or abuse within 3 months prior to enrolment.
• Individuals who are deemed at risk for aggressive behavior or suicide by their clinician
• Pregnant and breast-feeding subjects.
• Serious unstable physical illness
• Persons who have been deemed legally incapacitated according to Finnish law (Laki holhoustoimesta 1.4.1999/442, 3. luku, 18 §).
• Individuals who use H2-antagonists as prescribed by a physician
• Known allergy to famotidine or any other component of the Pepcidin® 40 mg tablet
• Glomerular Filtration Rate (GFR) according to the Cockcroft-Gault formula <30ml/min

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Helsinki University

Overall Clinical Trial Officials and Contacts

Jesper Ekelund, MD-PhD Principal Investigator Helsinki University  

Overall Contact: Jesper Ekelund, MD-PhD +358-50-3317987 Jesper.Ekelund@ktl.fi

Information obtained from ClinicalTrials.gov on January 08, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00565175

Study ID Number: 2006-006636-22

ClinicalTrials.gov Identifier: NCT00565175

Health Authority: Finland: National Agency for Medicines