Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia

Condition(s) targeted: Schizophrenia

Intervention: famotidine (Drug); Placebo (Microcrystallized cellulose) (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Helsinki University

Official(s) and/or principal investigator(s):
Jesper Ekelund, MD-PhD, Principal Investigator, Affiliation: Helsinki University

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

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.

Official title: Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia

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

Primary outcome: Scale for the Assessment of Negative Symptoms (SANS) score

Secondary outcome:

Positive and Negative Syndrome Scale (PANSS) score

Clinical Global Impression (CGI) score

Detailed description: 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.

Minimum age: 18 Years. Maximum age: 65 Years. Gender(s): Both.

Criteria:

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 < 30 ml/min

Jesper Ekelund, MD-PhD, Phone: +358-50-3317987, Email: Jesper.Ekelund@ktl.fi

Lohjan sairaanhoitoalue, Lohja 08450, Finland; Recruiting
Jarmo Laitinen, MD, Phone: +358-19-3801 700, Email: Jarmo.Laitinen@hus.fi
Hannu Saloheimo, MD, Sub-Investigator
Jarmo Laitinen, MD, Principal Investigator

Kellokosken sairaala, Kellokoski 04500, Finland; Recruiting
Grigori Joffe, MD-PhD, Phone: +358-9-2716 3220, Email: Grigori.Joffe@hus.fi
Grigori Joffe, MD-PhD, Principal Investigator

Peijaksen sairaala, Vantaa 01450, Finland; Not yet recruiting
Yrjo Lahteenlahti, MD, Phone: +358-9-471 66530, Email: Yrjo.Lahteenlahti@hus.fi
Yrjo Lahteenlahti, MD, Principal Investigator

HUCH Department of Psychiatry, Helsinki 10029, Finland; Recruiting
Jesper Ekelund, MD-PhD, Phone: +358-9-4711, Email: Jesper.Ekelund@hus.fi
Jesper Ekelund, MD-PhD, Principal Investigator

Starting date: January 2008
Ending date: December 2009
Last updated: May 28, 2009