Phosphodiesterase (PDE) Inhibitors Effect on Cognitive Deficits Associated to Schizophrenia

Early Phase 1

Terminated

• Conditions: Schizophrenia; Cognitive Deficits
• Interventions: Drug: Papaverine or placebo

• Registration Number: NCT01813955
• Lead Sponsor: University of Copenhagen

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.

Study Timeline

• Study Start: 2011-06
• Study First Submitted: 2011-09-19
• Study First Submitted QC: 2013-03-14
• Study First Posted: 2013-03-19
• Primary Completion: 2013-05
• Study Completion: 2013-06
• Status Verified: 2015-05
• Last Update Submitted: 2015-05-27
• Last Update Posted: 2015-05-28

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 5

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Papaverine	Papaverine or placebo	Patients will receive either Papaverine or placebo added to their current medical treatment. Then after one week, they will receive the other treatment (if it was placebo first, then it will be papaverine; if it was papaverine first, then it will be placebo)

Primary Outcome Measures

Name	Time	Method
psychophysiology	1 hour after intake of capsule with papaverine or placebo	Prepulse inhibition of the startle reflex, Mismatch negativity, P300 amplitude

Secondary Outcome Measures

Name	Time	Method
Hemodynamic changes	1 hour after intake of capsule with papaverine or placebo	Changes in Hemodynamics, as observed by MR techniques

Trial Locations

Locations (1)

Glostrup psychiatric center; 🇩🇰 Glostrup, Denmark