Clinical trial NCT01813955: Phosphodiesterase (PDE) Inhibitors Effect on Cognitive Deficits Associated to Schizophrenia
Official title: PDE Inhibitors Effect on Cognitive Deficits Associated to Schizophrenia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Schizophrenia
Cognitive Deficits
Keywords: phosphodiesterase inhibitor
Psychophysiology
Cognition
Schizophrenia
Papaverine
Lead sponsor: University of Copenhagen
Sponsor class: OTHER
Collaborators: name: Glostrup University Hospital, Copenhagen
First posted: 2013-03-19
Enrollment: 5
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: Phosphodiesterase (PDE) inhibitors represent a new group of potential antipsychotic compounds currently under development. One of these is papaverine, an inhibitor of the PDE 10 family. The class of PDE10 inhibitors have been reported as possible candidates in the treatment of schizophrenia, and may prove an attractive antipsychotic alternative due to the many side-effects of the currently available antipsychotics. It has been proposed from preclinical studies that PDE10 inhibitors have the potential to reduce cognitive deficits in schizophrenia and these findings need to be confirmed in a human population, in view of the fact that no other currently registered drug posses these unique properties.

The currently proposed project is designed to investigate whether the PDE10 inhibitor Papaverine indeed have the capacity to reduce cognitive deficits in schizophrenia patients. In order to accomplish this effect, Papaverine will be investigated in schizophrenia, with regards to symptomatology, hemodynamic, neurocognition and early information-processing.

Detailed description: The study has a double blind, balanced crossover design. Randomized, half of the subjects will be given Papaverine (PDE10 inhibitor, 300 mg orally) in the first session followed by placebo in the second, and the other half will be treated in the reverse order. There is a minimum of one month between the two test-sessions. After each of the two treatments, the subjects will be tested with both a psychophysiological (the Copenhagen Psychophysiological Test-Battery) and neuropsychological test-battery (tests from the Cambridge Neuropsychological Test Automated Battery, or "CANTAB"). The project has three phases: In the first phase 10 healthy subjects will be included to determine the kinetics of Papaverine-contained release capsules ; in the second phase 30 schizophrenia patients and 30 healthy subjects will be included to determine the impact on cognitive and sensory gating related deficits; Finally 10 Healthy subjects will be included to determine the effect of Papaverine on hemodynamical parameters by the means magnetic resonance scannings.

Eligibility criteria: Inclusion Criteria:

* Diagnosed Schizophrenia (WHO ICD 10)
* Treatment stable (no regulation in medicine for 6 weeks prior)
* Mono antipsychotic treatment
* No regular Antidepressants (PN accepted)
* No regular Benzodiazepines (PN accepted)

Exclusion Criteria:

* Dependence syndrome
* Severe physical illness
* MRI incompatible, non removable objects above shoulders

Primary outcomes:
measure: psychophysiology
timeFrame: 1 hour after intake of capsule with papaverine or placebo
Secondary outcomes:
measure: Hemodynamic changes
timeFrame: 1 hour after intake of capsule with papaverine or placebo
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Glostrup psychiatric center
Study officials:
affiliation: University of Copenhagen
name: Birte Glenthøj, Professor
role: STUDY_DIRECTOR
affiliation: University of Copenhagen
name: Mikkel E Sørensen, PHD student
role: PRINCIPAL_INVESTIGATOR
affiliation: Center for Neuropsychiatric Schizophrenia Research
name: Bob Oranje, PHD
role: STUDY_DIRECTOR
References: