Clinical trial NCT00565175: Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia
Official title: Histamine H2 Antagonism as Adjuvant Therapy in Treatment Resistant Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: Treatment resistant
Chronic
Lead sponsor: University of Helsinki
Sponsor class: OTHER
Collaborators: name: Finland: Lilly saatio foundation
First posted: 2007-11-29
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Scale for the Assessment of Negative Symptoms (SANS) score
timeFrame: 5 weeks
Secondary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS) score
timeFrame: 5 weeks
measure: Clinical Global Impression (CGI) score
timeFrame: 5 weeks
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: HUCH Department of Psychiatry
city: Kellokoski
country: Finland
facility: Kellokosken sairaala
city: Lohja
country: Finland
facility: Lohjan sairaanhoitoalue
city: Vaasa
country: Finland
facility: Vaasa Hospital District
city: Vantaa
country: Finland
facility: Peijaksen sairaala
Study officials:
affiliation: Helsinki University Central Hospital
name: Jesper Ekelund, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.